Journal of Xenobiotics

20 pages, 1162 KiB

Open AccessArticle

Time of Application of Desiccant Herbicides Affects Photosynthetic Pigments, Physiological Indicators, and the Quality of Cowpea Seeds

by Ester dos Santos Coêlho, João Everthon da Silva Ribeiro, Welder de Araújo Rangel Lopes, Anna Kézia Soares de Oliveira, Pablo Henrique de Almeida Oliveira, Gisele Lopes dos Santos, Ewerton da Silva Barbosa, Valécia Nogueira Santos e Silva, Hamurábi Anizio Lins, Clarisse Pereira Benedito, Lindomar Maria da Silveira, Antonio Cesar de Araujo Filho, Daniel Valadão Silva and Aurélio Paes Barros Júnior

J. Xenobiot. 2024, 14(3), 1312-1331; https://doi.org/10.3390/jox14030074 - 19 Sep 2024

Viewed by 1079

Abstract

Chemical desiccation is widely used in agriculture to anticipate harvest and mitigate the effects of adverse environmental conditions. It is applied to both grains and seeds. Although this practice is widely used, there are still significant gaps in understanding the effects of different [...] Read more.

Chemical desiccation is widely used in agriculture to anticipate harvest and mitigate the effects of adverse environmental conditions. It is applied to both grains and seeds. Although this practice is widely used, there are still significant gaps in understanding the effects of different herbicide application times on seed quality and plant physiological responses. The objective of this study was to evaluate the effects of different herbicide application times on cowpea, focusing on seed quality, physiological responses, and biochemical composition, including chlorophylls, carotenoids, sugars, and proline, under nocturnal desiccation. In the first experiment, eight herbicides and two mixtures were applied at night: diquat, flumioxazin, diquat + flumioxazin, glufosinate ammonium, saflufenacil, carfentrazone, diquat + carfentrazone, atrazine, and glyphosate. All of the tested herbicides caused a reduction in normal seedling formation, with the diquat + carfentrazone combination resulting in 100% abnormal seedlings. A significant decrease in chlorophyll levels (chlorophyll a: 63.5%, chlorophyll b: 50.2%) was observed using diquat, which indicates damage to photosynthetic processes, while the carotenoid content increased. Total soluble sugars and proline were also negatively impacted, reflecting physiological stress and metabolic changes in seedlings. In the second experiment, three application times were tested with diquat, diquat + flumioxazin, and diquat + carfentrazone. Nocturnal application showed the most significant reduction in chlorophyll levels and increased carotenoid levels. Application at noon and late afternoon also significantly changed the soluble sugar and proline levels. These results indicate that the herbicide application time directly influences the seeds’ physiological quality. Full article

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19 pages, 4695 KiB

Open AccessArticle

Assessment of the In Vitro Phosphatidylinositol Glycan Class A (PIG-A) Gene Mutation Assay Using Human TK6 and Mouse Hepa1c1c7 Cell Lines

by Wenhao Zhang, Charles A. Miller and Mark J. Wilson

J. Xenobiot. 2024, 14(3), 1293-1311; https://doi.org/10.3390/jox14030073 - 19 Sep 2024

Viewed by 654

Abstract

Gene mutations linked to diseases like cancer may be caused by exposure to environmental chemicals. The X-linked phosphatidylinositol glycan class A (PIG-A) gene, required for glycosylphosphatidylinositol (GPI) anchor biosynthesis, is a key target locus for in vitro genetic toxicity assays. Various organisms and [...] Read more.

Gene mutations linked to diseases like cancer may be caused by exposure to environmental chemicals. The X-linked phosphatidylinositol glycan class A (PIG-A) gene, required for glycosylphosphatidylinositol (GPI) anchor biosynthesis, is a key target locus for in vitro genetic toxicity assays. Various organisms and cell lines may respond differently to genotoxic agents. Here, we compared the mutagenic potential of directly genotoxic ethyl methane sulfonate (EMS) to metabolically activated pro-mutagenic polycyclic aromatic hydrocarbons (PAHs). The two classes of mutagens were compared in an in vitro PIG-A gene mutation test using the metabolically active murine hepatoma Hepa1c1c7 cell line and the human TK6 cell line, which has limited metabolic capability. Determination of cell viability is required for quantifying mutagenicity. Two common cell viability tests, the MTT assay and propidium iodide (PI) staining measured by flow cytometry, were evaluated. The MTT assay overestimated cell viability in adherent cells at high benzo[a]pyrene (B[a]P) exposure concentrations, so PI-based cytotoxicity was used in calculations. The spontaneous mutation rates for TK6 and Hepa1c1c7 cells were 1.87 and 1.57 per million cells per cell cycle, respectively. TK6 cells exposed to 600 µM and 800 µM EMS showed significantly higher mutation frequencies (36 and 47 per million cells per cell cycle, respectively). Exposure to the pro-mutagen benzo[a]pyrene (B[a]P, 10 µM) did not increase mutation frequency in TK6 cells. In Hepa1c1c7 cells, mutation frequencies varied across exposure groups (50, 50, 29, and 81 per million cells per cell cycle when exposed to 10 µM B[a]P, 5-methylcholanthrene (5-MC), chrysene, or 16,000 µM EMS, respectively). We demonstrate that the choice of cytotoxicity assay and cell line can determine the outcome of the Pig-A mutagenesis assay when assessing a specific mutagen. Full article

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25 pages, 7423 KiB

Open AccessReview

Lubricant Strategies in Osteoarthritis Treatment: Transitioning from Natural Lubricants to Drug Delivery Particles with Lubricant Properties

by Agnese Fragassi, Antonietta Greco and Roberto Palomba

J. Xenobiot. 2024, 14(3), 1268-1292; https://doi.org/10.3390/jox14030072 - 19 Sep 2024

Viewed by 808

Abstract

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, leading to pain and functional impairment. A key contributor to OA progression is the decline in cartilage lubrication. In physiological conditions, synovial fluid (SF) macromolecules like hyaluronic acid (HA), phospholipids, and lubricin [...] Read more.

Osteoarthritis (OA) is a debilitating joint disease characterized by cartilage degradation, leading to pain and functional impairment. A key contributor to OA progression is the decline in cartilage lubrication. In physiological conditions, synovial fluid (SF) macromolecules like hyaluronic acid (HA), phospholipids, and lubricin play a crucial role in the boundary lubrication of articular cartilage. In early OA, cartilage damage triggers inflammation, altering SF composition and compromising the lubrication layer. This increases friction between mating interfaces, worsening cartilage degradation and local inflammation. Therefore, early-stage restoration of lubrication (by injecting in the joint different classes of compounds and formulations) could alleviate, and potentially reverse, OA progression. In the light of this, a broad variety of lubricants have been investigated for their ability to reduce friction in OA joints and promote cartilage repair in clinical and preclinical studies. This review examines recent advancements in lubricant-based therapy for OA, focusing on natural, bioinspired, and alternative products. Starting from the currently applied therapy, mainly based on natural lubricants as HA, we will present their modified versions, either in hydrogel form or with specific biomimetic moieties with the aim of reducing their clearance from the joint and of enhancing their lubricating properties. Finally, the most advanced and recent formulation, represented by alternative strategies, will be proposed. Particular emphasis will be placed on those ones involving new types of hydrogels, microparticles, nanoparticles, and liposomes, which are currently under investigation in preclinical studies. The potential application of particles and liposomes could foster the transition from natural lubricants to Drug Delivery Systems (DDSs) with lubricant features; transition which could provide more complete OA treatments, by simultaneously providing lubrication replacement and sustained release of different payloads and active agents directly at the joint level. Within each category, we will examine relevant preclinical studies, highlighting challenges and future prospects. Full article

(This article belongs to the Section Nanotoxicology and Nanopharmacology)

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12 pages, 2364 KiB

Open AccessCommunication

Pregnenolone 16-Alpha Carbonitrile, an Agonist of Rodent Pregnane X Receptor, Regulates Testosterone Biosynthesis in Rodent Leydig Cells

by Julia M. Salamat, Elizabeth M. Ayala, Chen-Che J. Huang, Frank S. Wilbanks, Rachel C. Knight, Benson T. Akingbemi and Satyanarayana R. Pondugula

J. Xenobiot. 2024, 14(3), 1256-1267; https://doi.org/10.3390/jox14030071 - 16 Sep 2024

Viewed by 740

Abstract

Leydig cells (LCs) in the testes produce the male sex hormone testosterone (T). Several xenobiotics, including clinical drugs, supplements, and environmental chemicals, are known to disrupt T homeostasis. Notably, some of these xenobiotics are known to activate the pregnane X receptor (PXR), a [...] Read more.

Leydig cells (LCs) in the testes produce the male sex hormone testosterone (T). Several xenobiotics, including clinical drugs, supplements, and environmental chemicals, are known to disrupt T homeostasis. Notably, some of these xenobiotics are known to activate the pregnane X receptor (PXR), a ligand-dependent nuclear receptor. However, it is currently unknown whether PXR is expressed in LCs and whether PXR activation alters T synthesis in rodent LCs. Therefore, in this study, we sought to determine whether PXR is expressed in rodent LCs and whether pregnenolone 16-alpha carbonitrile (PCN), the prototype agonist of rodent PXR, regulates T biosynthesis in rodent LCs. Hormonal as well as protein and gene expression analyses were conducted in rat primary LCs and MA-10 mouse Leydig cells. Results showed that PXR was expressed at the mRNA and protein level in both rat primary LCs and MA-10 cells. Incubation of rat primary LCs with PCN resulted in a significant decrease in T secretion. This PCN-induced decrease in T secretion was associated with decreased protein expression of key steroidogenic enzymes such as 3β-HSD and CYP17A1. RNA-seq results from MA-10 cells showed that PCN down-regulated the transcripts of steroidogenic enzymes and proteins involved in the T synthesis pathway. Together, these results suggest that PCN, an agonist of rodent PXR, can regulate T biosynthesis in rodent LCs by down-regulating the expression of the steroidogenic enzymes involved in T biosynthesis. Our results are significant as they provide a potential novel mechanism for disruption of testosterone homeostasis by a variety of xenobiotics. Full article

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18 pages, 4434 KiB

Open AccessArticle

Resolving Coffee Waste and Water Pollution—A Study on KOH-Activated Coffee Grounds for Organophosphorus Xenobiotics Remediation

by Vedran Milanković, Tamara Tasić, Igor A. Pašti and Tamara Lazarević-Pašti

J. Xenobiot. 2024, 14(3), 1238-1255; https://doi.org/10.3390/jox14030070 - 10 Sep 2024

Viewed by 2773

Abstract

This study investigates using KOH-activated coffee grounds (KACGs) as an effective adsorbent for removing organophosphorus xenobiotics malathion and chlorpyrifos from water. Malathion and chlorpyrifos, widely used as pesticides, pose significant health risks due to their neurotoxic effects and environmental persistence. Spent coffee grounds, [...] Read more.

This study investigates using KOH-activated coffee grounds (KACGs) as an effective adsorbent for removing organophosphorus xenobiotics malathion and chlorpyrifos from water. Malathion and chlorpyrifos, widely used as pesticides, pose significant health risks due to their neurotoxic effects and environmental persistence. Spent coffee grounds, abundant biowaste from coffee production, are chemically activated with KOH to enhance their adsorptive capacity without thermal treatment. This offers a sustainable solution for biowaste management and water remediation. Adsorption kinetics indicating rapid initial adsorption with high affinity were observed, particularly for chlorpyrifos. Isotherm studies confirmed favorable adsorption conditions, with higher maximum adsorption capacities for chlorpyrifos compared to malathion (15.0 ± 0.1 mg g⁻¹ for malathion and 22.3 ± 0.1 mg g⁻¹ for chlorpyrifos), highlighting its potential in mitigating water pollution. Thermodynamic analysis suggested the adsorption process was spontaneous but with the opposite behavior for the investigated pesticides. Malathion interacts with KACGs via dipole–dipole and dispersion forces, while chlorpyrifos through π–π stacking with aromatic groups. The reduction in neurotoxic risks associated with pesticide exposure is also shown, indicating that no more toxic products were formed during the remediation. This research contributes to sustainable development goals by repurposing biowaste and addressing water pollution challenges through innovative adsorbent materials. Full article

(This article belongs to the Section Ecotoxicology)

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17 pages, 1689 KiB

Open AccessArticle

Assessing the Effects of a Diet of BPA Analogue-Exposed Microalgae in the Clam Ruditapes philippinarum

by Jacopo Fabrello, Michela Dalla Fontana, Noemi Gaiani, Maria Ciscato, Marco Roverso, Sara Bogialli and Valerio Matozzo

J. Xenobiot. 2024, 14(3), 1221-1237; https://doi.org/10.3390/jox14030069 - 6 Sep 2024

Viewed by 687

Abstract

In our previous study, we demonstrated that the microalgae Phaeodactylum tricornutum can bioaccumulate bisphenol A analogues. Since this microalgae species is part of the diet of marine filter-feeding organisms, such as bivalves, in this study we tested the hypothesis that a diet based [...] Read more.

In our previous study, we demonstrated that the microalgae Phaeodactylum tricornutum can bioaccumulate bisphenol A analogues. Since this microalgae species is part of the diet of marine filter-feeding organisms, such as bivalves, in this study we tested the hypothesis that a diet based on exposed microalgae can exert negative effects on the clam Ruditapes philippinarum. Microalgae were exposed for 7 days to 300 ng/L of bisphenol AF (BPAF), bisphenol F (BPF), and bisphenol S (BPS), alone or as a mixture (MIX), to allow bioaccumulation. Microalgae were then supplied as food to bivalves. After 7 and 14 days of diet, the effects of exposed microalgae were evaluated on a battery of biomarkers measured in haemolymph/haemocytes, gills and digestive glands of clams. In addition, bioaccumulation of the three bisphenols was investigated in clams by UHPLC-HRMS. The results obtained demonstrated that total haemocyte count (THC) increased in clams following ingestion for 7 days of BPAF- and BPF-exposed microalgae, while BPS-exposed microalgae significantly reduced THC after 14 days of diet. MIX- and BPS-exposed microalgae increased haemocyte proliferation. The diet of exposed microalgae affected acid and alkaline phosphatase activity in clams, with an opposite response between haemolymph and haemocytes. Regarding antioxidants, an increase in catalase activity was observed in clams after ingestion of BPA analogue-exposed microalgae. The results also demonstrated marked oxidative stress in gills, the first tissue playing an important role in the feeding process. Oxidative damage was recorded in both the gills and digestive glands of clams fed BPA analogue-exposed microalgae. Alterations in epigenetic-involved enzyme activity were also found, demonstrating for the first time that BPA analogue-exposed food can alter epigenetic mechanisms in marine invertebrates. No bioaccumulation of BPA analogues was detected in clam soft tissues. Overall, this study demonstrated that a diet of BPA analogue-exposed microalgae can induce significant alterations of some important biological responses of R. philippinarum. To our knowledge, this is the first study demonstrating the effects of ingestion of BPA analogue-exposed microalgae in the clam R. philippinarum, suggesting a potential ecotoxicological risk for the marine food chain, at least at the first levels. Full article

(This article belongs to the Special Issue Feature Papers in Ecotoxicology)

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20 pages, 6109 KiB

Open AccessArticle

Bisphenol F and Bisphenol S in a Complex Biomembrane: Comparison with Bisphenol A

by José Villalaín

J. Xenobiot. 2024, 14(3), 1201-1220; https://doi.org/10.3390/jox14030068 - 4 Sep 2024

Viewed by 1019

Abstract

Bisphenols are a group of endocrine-disrupting chemicals used worldwide for the production of plastics and resins. Bisphenol A (BPA), the main bisphenol, exhibits many unwanted effects. BPA has, currently, been replaced with bisphenol F (BPF) and bisphenol S (BPS) in many applications in [...] Read more.

Bisphenols are a group of endocrine-disrupting chemicals used worldwide for the production of plastics and resins. Bisphenol A (BPA), the main bisphenol, exhibits many unwanted effects. BPA has, currently, been replaced with bisphenol F (BPF) and bisphenol S (BPS) in many applications in the hope that these molecules have a lesser effect on metabolism than BPA. Since bisphenols tend to partition into the lipid phase, their place of choice would be the cellular membrane. In this paper, I carried out molecular dynamics simulations to compare the localization and interactions of BPA, BPF, and BPS in a complex membrane. This study suggests that bisphenols tend to be placed at the membrane interface, they have no preferred orientation inside the membrane, they can be in the monomer or aggregated state, and they affect the biophysical properties of the membrane lipids. The properties of bisphenols can be attributed, at least in part, to their membranotropic effects and to the modulation of the biophysical membrane properties. The data support that both BPF and BPS, behaving in the same way in the membrane as BPA and with the same capacity to accumulate in the biological membrane, are not safe alternatives to BPA. Full article

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14 pages, 1705 KiB

Open AccessArticle

Application of Microbiological Screening Tests in Assessment of Environmental Exposure to Antibiotics: Preliminary Studies

by Daria Madej-Knysak, Ewa Adamek, Leon Kośmider and Wojciech Baran

J. Xenobiot. 2024, 14(3), 1187-1200; https://doi.org/10.3390/jox14030067 - 4 Sep 2024

Viewed by 620

Abstract

Contact of aquatic microbiocenoses with antibiotics present in the environment can cause the former to develop resistance to antimicrobial drugs. Therefore, the search for methods to detect antibiotics and drug-resistant microorganisms in the environment is important. The presented paper proposes a simple procedure [...] Read more.

Contact of aquatic microbiocenoses with antibiotics present in the environment can cause the former to develop resistance to antimicrobial drugs. Therefore, the search for methods to detect antibiotics and drug-resistant microorganisms in the environment is important. The presented paper proposes a simple procedure to assess environmental exposure to antibiotics and the presence of non-susceptible microorganisms. Medium solutions with selected antibiotics and a microbial growth indicator were applied to test plates, and were inoculated with water samples from various ecosystems. After incubation, the susceptibility of the microorganisms to antibiotics was determined and presented in chronic microbial toxic concentration (MTC) values. It was confirmed that the presented procedure enables the assessment of the antibiotic susceptibility and adaptation potential of unselected microorganisms from different aquatic ecosystems. However, the MTC values depend on the inoculum volume, the density and seasonal activity of the microorganisms, the method of inoculum preparation, and the incubation time of the test plate. The described procedure may be practically applied as a screening test to identify the presence of drug-resistant microorganisms. Additionally, it may also be suitable as a method to assess environmental exposure to antibiotics. However, prior standardisation is required before implementing this procedure in quantitative studies. Full article

(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)

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22 pages, 6095 KiB

Open AccessArticle

Persistent Organic Pollutants in Tagus Estuary Salt Marshes: Patterns of Contamination and Plant Uptake

by Ricardo Cruz de Carvalho, João Cardoso, João Albuquerque Carreiras, Paula Santos, Carla Palma and Bernardo Duarte

J. Xenobiot. 2024, 14(3), 1165-1186; https://doi.org/10.3390/jox14030066 - 2 Sep 2024

Viewed by 711

Abstract

The presence of anthropogenic compounds, including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), was studied in three salt marshes within the Tagus estuary, Portugal, along an anthropogenic pressure gradient. Results revealed differences in OCPs and PCBs among the marshes, with differing concentration levels. [...] Read more.

The presence of anthropogenic compounds, including organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs), was studied in three salt marshes within the Tagus estuary, Portugal, along an anthropogenic pressure gradient. Results revealed differences in OCPs and PCBs among the marshes, with differing concentration levels. Specifically, one marsh, with surrounding agricultural activity, showed the highest OCP concentrations, while another, with a historical industrial past, exhibited elevated PCB levels. In contrast, a third marsh, part of a natural reserve, displayed comparatively lower concentrations of both substances. Sediment concentrations, likely influenced by agricultural practices, were found to be comparable to or higher than those observed in other Portuguese estuaries. The halophyte Spartina maritima was found to absorb OCPs, particularly in its aboveground tissues, suggesting bioaccumulation within the plant. Additionally, PCB levels appeared to be influenced by industrial history, with one marsh displaying notably higher concentrations. In conclusion, the persistence of organochlorine compounds in the salt marsh ecosystems notwithstanding the regulatory prohibitions implemented in the 1990s highlights the need for continuous monitoring and study of such sites and the necessity of remediation practices, which are imperative to mitigate ecological and health risks in these polluted salt marshes. Full article

(This article belongs to the Section Emerging Chemicals)

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22 pages, 1930 KiB

Open AccessArticle

Novel Technique for Simultaneous Ethylene Glycol and Its Metabolites Determination in Human Whole Blood and Urine Samples Using GC–QqQ–MS/MS

by Kaja Tusiewicz, Olga Wachełko, Marcin Zawadzki and Paweł Szpot

J. Xenobiot. 2024, 14(3), 1143-1164; https://doi.org/10.3390/jox14030065 - 27 Aug 2024

Viewed by 1058

Abstract

Toxicological analyses often necessitate the identification of compounds belonging to diverse functional groups. For GC–MS analyses, derivatization of compounds belonging to different functional groups can pose a challenge and requires the development of comprehensive methods of analysis. One example could be ethylene glycol, [...] Read more.

Toxicological analyses often necessitate the identification of compounds belonging to diverse functional groups. For GC–MS analyses, derivatization of compounds belonging to different functional groups can pose a challenge and requires the development of comprehensive methods of analysis. One example could be ethylene glycol, whose widespread use is related to possible unintentional or suicidal intoxications. This fact clearly indicates the need to develop sensitive methods for the determination of ethylene glycol and its metabolites in biological material, as only such complex analysis allows for proper toxicological expertise. A simultaneous GC–QqQ–MS/MS method for the determination of ethylene glycol together with its metabolites, glyoxal and glycolic acid, as well as the detection of glyoxylic acid and oxalic acid, was developed and fully validated. A novel approach for simultaneous derivatization of substances from different groups (alcohols, aldehydes, and carboxylic acids) was established. Sample preparation included the addition of three internal standards (BHB-d₄, ethylene glycol-d₄ and methylglyoxal), precipitation with acetonitrile and subsequent derivatization with N-tert-butyldimethylsilyl-N-methyltrifluoroacetamide (MTBSTFA), as well as pentafluorophenylhydrazine (PFPH). Detection was carried out with the use of triple quadrupole mass spectrometer. The ionization method was electron impact, and quantitative analysis was carried out in multiple reaction monitoring mode. The lower limit of quantification was 1 μg/mL, 0.1 μg/mL, and 500 μg/mL for ethylene glycol, glyoxal, and glycolic acid, respectively. The presented method was applied in three authentic postmortem cases of ethylene glycol intoxication. Full article

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13 pages, 2463 KiB

Open AccessArticle

Vanadium Toxicity Is Altered by Global Warming Conditions in Sea Urchin Embryos: Metal Bioaccumulation, Cell Stress Response and Apoptosis

by Chiara Martino, Fabiana Geraci, Rosaria Scudiero, Giampaolo Barone, Flores Naselli and Roberto Chiarelli

J. Xenobiot. 2024, 14(3), 1130-1142; https://doi.org/10.3390/jox14030064 - 22 Aug 2024

Viewed by 582

Abstract

In recent decades, the global vanadium (V) industry has been steadily growing, together with interest in the potential use of V compounds as therapeutics, leading to V release in the marine environment and making it an emerging pollutant. Since climate change can amplify [...] Read more.

In recent decades, the global vanadium (V) industry has been steadily growing, together with interest in the potential use of V compounds as therapeutics, leading to V release in the marine environment and making it an emerging pollutant. Since climate change can amplify the sensitivity of marine organisms already facing chemical contamination in coastal areas, here, for the first time, we investigated the combined impact of V and global warming conditions on the development of Paracentrotus lividus sea urchin embryos. Embryo-larval bioassays were carried out in embryos exposed for 24 and 48 h to sodium orthovanadate (Na₃VO₄) under conditions of near-future ocean warming projections (+3 °C, 21 °C) and of extreme warming at present-day marine heatwave conditions (+6 °C, 24 °C), compared to the control temperature (18 °C). We found that the concomitant exposure to V and higher temperature caused an increased percentage of malformations, impaired skeleton growth, the induction of heat shock protein (HSP)-mediated cell stress response and the activation of apoptosis. We also found a time- and temperature-dependent increase in V bioaccumulation, with a concomitant reduction in intracellular calcium ions (Ca²⁺). This work demonstrates that embryos’ sensitivity to V pollution is increased under global warming conditions, highlighting the need for studies on multiple stressors. Full article

(This article belongs to the Topic Environmental Toxicology and Human Health—2nd Edition)

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21 pages, 1779 KiB

Open AccessReview

The Therapeutic Mechanisms of Honey in Mitigating Toxicity from Anticancer Chemotherapy Toxicity: A Review

by Debalina Bose, Ademola C. Famurewa, Aman Akash and Eman M. Othman

J. Xenobiot. 2024, 14(3), 1109-1129; https://doi.org/10.3390/jox14030063 - 20 Aug 2024

Viewed by 1553

Abstract

Within the domain of conventional oncochemotherapeutics, anticancer chemotherapy (AC) has emerged as a potent strategy for the treatment of cancers. AC is the mainstay strategy for solid and non-solid cancer treatment. Its mechanistic action targets the blockage of DNA transcription and the dysregulation [...] Read more.

Within the domain of conventional oncochemotherapeutics, anticancer chemotherapy (AC) has emerged as a potent strategy for the treatment of cancers. AC is the mainstay strategy for solid and non-solid cancer treatment. Its mechanistic action targets the blockage of DNA transcription and the dysregulation of cell cycle machinery in cancer cells, leading to the activation of death pathways. However, the attendant side effect of toxicity inflicted by AC on healthy tissues presents a formidable challenge. The crucial culprit in the AC side effect of toxicity is unknown, although oxidative stress, mitochondrial impairment, inflammatory cascades, autophagy dysregulation, apoptosis, and certain aberrant signaling have been implicated. Honey is a natural bee product with significant health benefits and pharmacological properties. Interestingly, the literature reports that honey may proffer a protection mechanism for delicate tissue/organs against the side effect of toxicity from AC. Thus, this review delves into the prospective role of honey as an alleviator of the AC side effect of toxicity; it provides an elucidation of the mechanisms of AC toxicity and honey’s molecular mechanisms of mitigation. The review endeavors to unravel the specific molecular cascades by which honey orchestrates its mitigating effects, with the overarching objective of refining its application as an adjuvant natural product. Honey supplementation prevents AC toxicity via the inhibition of oxidative stress, NF-κB-mediated inflammation, and caspase-dependent apoptosis cascades. Although there is a need for increased mechanistic studies, honey is a natural product that could mitigate the various toxicities induced by AC. Full article

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16 pages, 1860 KiB

Open AccessArticle

Associations between Non-Essential Trace Elements in Women’s Biofluids and IVF Outcomes in Euploid Single-Embryo Transfer Cycles

by Roberto Gonzalez-Martin, Andrea Palomar, Silvia Perez-Deben, Stefania Salsano, Alicia Quiñonero, Laura Caracena, Isabel Rucandio, Rocio Fernandez-Saavedra, Rodolfo Fernandez-Martinez, Estefania Conde-Vilda, Alberto J. Quejido, Juan Giles, Carmen Vidal, Jose Bellver and Francisco Dominguez

J. Xenobiot. 2024, 14(3), 1093-1108; https://doi.org/10.3390/jox14030062 - 8 Aug 2024

Viewed by 893

Abstract

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish [...] Read more.

Previous studies have found inconsistent associations between heavy metals and metalloids (cadmium, lead, mercury, and arsenic), and reproductive outcomes. The biofluid concentrations of ten non-essential trace elements (Hg, Pb, As, Ba, Sr, Rb, Cs, Sn, Ni, and Co) were evaluated in 51 Spanish women undergoing ICSI, PGT-A, and SET/FET. Nine out of ten non-essential elements were detectable in follicular fluid, whole blood, and urine collected the day of vaginal oocyte retrieval (VOR) and the day of embryo transfer and then analyzed by ICP-MS or Tricell DMA-80 for mercury. Elevated mercury and strontium concentrations in follicular fluid were associated with poor ovarian response and preimplantation outcomes. Worst preimplantation outcomes were also identified in women with elevated whole-blood strontium or mercury, urinary arsenic, barium, and tin the day of VOR. High concentrations of urinary rubidium on VOR day were linked with enhanced fertilization and blastocyst development. Excessive titanium in whole blood was associated with lower odds of implantation, clinical pregnancy, and achieving a live birth in a given IVF cycle. Excessive urinary arsenic on the day of embryo transfer was associated with lower odds of live birth. Although these preliminary results need to be confirmed in larger populations, distinguishing organic and inorganic element forms, our findings show that some non-essential elements have a detrimental impact on human IVF outcomes. Full article

(This article belongs to the Section Emerging Chemicals)

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14 pages, 3990 KiB

Open AccessArticle

Berberine Attenuates Acetamiprid Exposure-Induced Mitochondrial Dysfunction and Apoptosis in Rats via Regulating the Antioxidant Defense System

by Annu Phogat, Jagjeet Singh, Reena Sheoran, Arun Hasanpuri, Aakash Chaudhary, Shakti Bhardwaj, Sandeep Antil, Vijay Kumar, Chandra Prakash and Vinay Malik

J. Xenobiot. 2024, 14(3), 1079-1092; https://doi.org/10.3390/jox14030061 - 7 Aug 2024

Cited by 1 | Viewed by 1210

Abstract

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of [...] Read more.

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of its therapeutic and prophylactic actions. Therefore, this study evaluated the effects of BBR on ACMP-mediated alterations in mitochondrial functions and apoptosis in rat liver tissue. Male Wistar rats were divided into four groups: (I) control, (II) BBR-treated, (III) ACMP-exposed, and (IV) BBR+ACMP co-treated groups. The doses of BBR (150 mg/kg b.wt) and ACMP (1/10 of LD_50, i.e., 21.7 mg/kg b.wt) were given intragastrically for 21 consecutive days. The results showed that the administration of ACMP diminished mitochondrial complex activity, downregulated complex I (ND1 and ND2) and complex IV (COX1 and COX4) subunit mRNA expression, depleted the antioxidant defense system, and induced apoptosis in rat liver. BBR pre-treatment significantly attenuated ACMP-induced mitochondrial dysfunction by maintaining mitochondrial complex activity and upregulating ND1, ND2, COX1, and COX4 mRNA expression. BBR reversed ACMP-mediated apoptosis by diminishing Bax and caspase-3 and increasing the Bcl-2 protein level. BBR also improved the mitochondrial antioxidant defense system by upregulating mRNA expression of PGC-1α, MnSOD, and UCP-2 in rat liver tissue. This study is the first to evaluate the protective potential of BBR against pesticide-induced mitochondrial dysfunction in liver tissue. In conclusion, BBR offers protection against ACMP-induced impairment in mitochondrial functions by maintaining the antioxidant level and modulating the apoptotic cascade. Full article

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15 pages, 3134 KiB

Open AccessArticle

Estrogenic Responsiveness of Brown Trout Primary Hepatocyte Spheroids to Environmental Levels of 17α-Ethinylestradiol

by Rodrigo F. Alves, Célia Lopes, Eduardo Rocha and Tânia Vieira Madureira

J. Xenobiot. 2024, 14(3), 1064-1078; https://doi.org/10.3390/jox14030060 - 6 Aug 2024

Cited by 1 | Viewed by 886

Abstract

Three-dimensional (3D) fish hepatocyte cultures are promising alternative models for replicating in vivo data. Few studies have attempted to characterise the structure and function of fish 3D liver models and illustrate their applicability. This study aimed to further characterise a previously established spheroid [...] Read more.

Three-dimensional (3D) fish hepatocyte cultures are promising alternative models for replicating in vivo data. Few studies have attempted to characterise the structure and function of fish 3D liver models and illustrate their applicability. This study aimed to further characterise a previously established spheroid model obtained from juvenile brown trout (Salmo trutta) primary hepatocytes under estrogenic stimulation. The spheroids were exposed for six days to environmentally relevant concentrations of 17α-ethinylestradiol—EE2 (1–100 ng/L). The mRNA levels of peroxisome (catalase—Cat and urate oxidase—Uox), lipid metabolism (acyl-CoA long chain synthetase 1—Acsl1, apolipoprotein AI—ApoAI, and fatty acid binding protein 1—Fabp1), and estrogen-related (estrogen receptor α—ERα, estrogen receptor β—ERβ, vitellogenin A—VtgA, zona pellucida glycoprotein 2.5—ZP2.5, and zona pellucida glycoprotein 3a.2—ZP3a.2) target genes were evaluated by quantitative real-time polymerase chain reaction. Immunohistochemistry was used to assess Vtg and ZP protein expressions. At the highest EE2 concentration, VtgA and ZP2.5 genes were significantly upregulated. The remaining target genes were not significantly altered by EE2. Vtg and ZP immunostaining was consistently increased in spheroids exposed to 50 and 100 ng/L of EE2, whereas lower EE2 levels resulted in a weaker signal. EE2 did not induce significant changes in the spheroids’ viability and morphological parameters. This study identified EE2 effects at environmentally relevant doses in trout liver spheroids, indicating its usefulness as a proxy for in vivo impacts of xenoestrogens. Full article

(This article belongs to the Special Issue Feature Papers in Ecotoxicology)

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13 pages, 455 KiB

Open AccessArticle

Association between Liver and Kidney Function and Birth Outcomes in Pregnant Surinamese Women Exposed to Mercury and Lead in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH) Environmental Epidemiologic Cohort Study

by Sheila Kort, Jeffrey Wickliffe, Arti Shankar, Hannah H. Covert, Maureen Lichtveld and Wilco Zijlmans

J. Xenobiot. 2024, 14(3), 1051-1063; https://doi.org/10.3390/jox14030059 - 1 Aug 2024

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Abstract

Exposure to mercury (Hg) and lead (Pb), in combination with liver and kidney impairment, may result in adverse birth outcomes. From 408 women in the age range of 16 to 46 years, living in rural and urban areas in the interior of Suriname, [...] Read more.

Exposure to mercury (Hg) and lead (Pb), in combination with liver and kidney impairment, may result in adverse birth outcomes. From 408 women in the age range of 16 to 46 years, living in rural and urban areas in the interior of Suriname, we looked at the association between adverse birth outcomes and exposure to Hg and Pb in combination with liver and kidney function. This group of women represented a subcohort of pregnant women who participated in the Caribbean Consortium for Research in Environmental and Occupational Health (CCREOH)—Meki Tamara study. Liver function was assessed by measuring aspartate amino transferase (AST), alanine amino transferase (ALT), and gamma-glutamyl transferase (GGT). Kidney function was assessed by measuring creatinine, urea, and cystatin C. We defined preterm births as birth before 37 weeks of gestation, low birthweight as birthweight < 2500 g, and low Apgar score as a score < 7 at 5 min, and these were used as indicators for adverse birth outcomes. Small size for gestational age was defined as gestational age < −2SD weight for GA. We found significant statistical associations between biomarkers for liver and kidney functions and adverse birth outcomes Apgar score and gestational age. No significant association was found between heavy metals Hg and lead and adverse birth outcomes. Full article

(This article belongs to the Topic Disease Risks and Toxic Pathway from Environmental Chemical Exposure)

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15 pages, 2670 KiB

Open AccessArticle

Prenatal Exposure to Bisphenol A and/or Diethylhexyl Phthalate Impacts Brain Monoamine Levels in Rat Offspring

by Amrita Kaimal, Jessica M. Hooversmith, Maryam H. Al Mansi, Philip V. Holmes, Puliyur S. MohanKumar and Sheba M. J. MohanKumar

J. Xenobiot. 2024, 14(3), 1036-1050; https://doi.org/10.3390/jox14030058 - 1 Aug 2024

Viewed by 821

Abstract

This study examines the sex-specific effects of gestational exposure (days 6–21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague–Dawley rats were orally administered [...] Read more.

This study examines the sex-specific effects of gestational exposure (days 6–21) to endocrine-disrupting chemicals such as bisphenol A (BPA), diethylhexyl phthalate (DEHP), or their combination on brain monoamine levels that play an important role in regulating behavior. Pregnant Sprague–Dawley rats were orally administered saline, low doses (5 µg/kg BW/day) of BPA or DEHP, and their combination or a high dose (7.5 mg/kg BW/day) of DEHP alone or in combination with BPA during pregnancy. The offspring were subjected to a behavioral test and sacrificed in adulthood, and the brains were analyzed for neurotransmitter levels. In the paraventricular nucleus, there was a marked reduction in dopamine levels (p < 0.01) in male offspring from the BPA, DEHP, and B + D (HD) groups, which correlated well with their shock probe defensive burying times. Neurotransmitter changes in all brain regions examined were significant in female offspring, with DEHP (HD) females being affected the most, followed by the B + D groups. BPA and/or DEHP (LD) increased monoamine turnover in a region-specific manner in male offspring (p < 0.05). Overall, prenatal exposure to BPA, DEHP, or their combination alters monoamine levels in a brain region-specific, sex-specific, and dose-dependent manner, which could have implications for their behavioral and neuroendocrine effects. Full article

(This article belongs to the Special Issue The Role of Endocrine-Disrupting Chemicals in the Human Health)

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13 pages, 3020 KiB

Open AccessArticle

Incorporating Tissue-Specific Gene Expression Data to Improve Chemical–Disease Inference of in Silico Toxicogenomics Methods

by Shan-Shan Wang, Chia-Chi Wang, Chien-Lun Wang, Ying-Chi Lin and Chun-Wei Tung

J. Xenobiot. 2024, 14(3), 1023-1035; https://doi.org/10.3390/jox14030057 - 31 Jul 2024

Viewed by 795

Abstract

In silico toxicogenomics methods are resource- and time-efficient approaches for inferring chemical–protein–disease associations with potential mechanism information for exploring toxicological effects. However, current in silico toxicogenomics systems make inferences based on only chemical–protein interactions without considering tissue-specific gene/protein expressions. As a result, inferred [...] Read more.

In silico toxicogenomics methods are resource- and time-efficient approaches for inferring chemical–protein–disease associations with potential mechanism information for exploring toxicological effects. However, current in silico toxicogenomics systems make inferences based on only chemical–protein interactions without considering tissue-specific gene/protein expressions. As a result, inferred diseases could be overpredicted with false positives. In this work, six tissue-specific expression datasets of genes and proteins were collected from the Expression Atlas. Genes were then categorized into high, medium, and low expression levels in a tissue- and dataset-specific manner. Subsequently, the tissue-specific expression datasets were incorporated into the chemical–protein–disease inference process of our ChemDIS system by filtering out relatively low-expressed genes. By incorporating tissue-specific gene/protein expression data, the enrichment rate for chemical–disease inference was largely improved with up to 62.26% improvement. A case study of melamine showed the ability of the proposed method to identify more specific disease terms that are consistent with the literature. A user-friendly user interface was implemented in the ChemDIS system. The methodology is expected to be useful for chemical–disease inference and can be implemented for other in silico toxicogenomics tools. Full article

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20 pages, 109182 KiB

Open AccessArticle

In Vivo Antischistosomicidal and Immunomodulatory Effects of Dietary Supplementation with Taraxacum officinale

by Amany Ebrahim Nofal, Amal Mohamed Shaaban, Hany Mohammed Ibrahim, Faten Abouelmagd and Azza Hassan Mohamed

J. Xenobiot. 2024, 14(3), 1003-1022; https://doi.org/10.3390/jox14030056 - 29 Jul 2024

Viewed by 882

Abstract

Bilharziasis is a widespread trematode parasite that poses a severe public health burden. Dandelion (Taraxacum officinale) has several pharmacological and traditional properties critical for treating several hepatic disorders. The present study was designed to assess the potential efficacy of T. officinale [...] Read more.

Bilharziasis is a widespread trematode parasite that poses a severe public health burden. Dandelion (Taraxacum officinale) has several pharmacological and traditional properties critical for treating several hepatic disorders. The present study was designed to assess the potential efficacy of T. officinale root (TOR) dietary supplementation with or without praziquantel (PZQ) against liver and intestinal disorders in mice infected with Schistosoma mansoni. This study was conducted on five groups; G1: uninfected control, G2: untreated S. mansoni-infected mice, G3: infected animals treated with 250 mg/kg PZQ for three alternative days, G4: infected animals were orally administered 600 mg/kg bw TOR daily for 10 days, and G5: infected animals that received both PZQ and TOR as previously described. The current findings after different treatments indicated topographical scanning electron microscopy alterations of male adult worms and a critical reduction in worm burden, ova count, granuloma diameter, hepatic and intestinal histological abnormalities, fibrosis, immunohistochemical expression of CD3⁺ and CD20⁺ cells, oxidative stress, and interleukin-10, also upregulation of interferon-gamma, and antioxidant enzymes, when compared to the infected untreated mice. The best results were obtained in mice administered PZQ+TOR together because of their antioxidant properties and ability to promote the host immune response to parasitic infection. Full article

(This article belongs to the Section Natural Products/Herbal Medicines)

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14 pages, 3334 KiB

Open AccessArticle

Pollution of Beach Sands of the Ob River (Western Siberia) with Microplastics and Persistent Organic Pollutants

by Yulia A. Frank, Yulia S. Sotnikova, Vasiliy Yu. Tsygankov, Aleksey R. Rednikin, Maksim M. Donets, Elena V. Karpova, Maksim A. Belanov, Svetlana Rakhmatullina, Aleksandra D. Borovkova, Dmitriy N. Polovyanenko and Danil S. Vorobiev

J. Xenobiot. 2024, 14(3), 989-1002; https://doi.org/10.3390/jox14030055 - 25 Jul 2024

Viewed by 1123

Abstract

Microplastics (MPs) in aquatic environments can be associated with various substances, including persistent organic pollutants, which add to the problem of plastic ecotoxicity. The abundance of 1–5 mm microplastics and concentrations of particle-adsorbed organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sandy sediments [...] Read more.

Microplastics (MPs) in aquatic environments can be associated with various substances, including persistent organic pollutants, which add to the problem of plastic ecotoxicity. The abundance of 1–5 mm microplastics and concentrations of particle-adsorbed organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) in sandy sediments from three beaches in recreational areas along the upper Ob River in Western Siberia were assessed. MP pollution levels in the Ob River beach sands ranged from 24 ± 20.7 to 104 ± 46.2 items m⁻² or, in terms of mass concentration, from 0.26 ± 0.21 to 1.22 ± 0.39 mg m⁻². The average abundance of MP particles reached 0.67 ± 0.58 items kg⁻¹ or 8.22 ± 6.13 μg kg⁻¹ in the studied sediments. MP concentrations were significantly higher in number (p < 0.05) and mass (p < 0.01) at the riverbank site downstream of the Novosibirsk wastewater treatment plant (WWTP) outfall compared to these at the upstream and more distant beaches. Most MPs (70–100%) were represented by irregularly shaped fragments. The polymer composition of MPs varied between sites, with a general predominance of polyethylene (PE). The study revealed associations of MPs with PCBs and OCPs not previously detected in the riverbed and beach sediments, suggesting that these substances are circulating in the Ob River basin. Although MP concentrations were higher downstream of the WWTP, the maximum levels of particle-associated OCPs were observed in the beach sands of the site farthest from the urban agglomeration. The pesticides γ-HCH, 4,4-DDT, and 4,4-DDE were detected on MPs at relatively low concentrations. PCBs were more abundant in the studied samples, including 118 dioxin-like congener. The results obtained indicate that the Ob River is susceptible to plastic and persistent organic pollutant (POP) contamination and serve as a starting point for further studies and practical solutions to the problem. Full article

(This article belongs to the Section Emerging Chemicals)

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19 pages, 6798 KiB

Open AccessArticle

The Impact of Metolachlor Applications and Phytoremediation Processes on Soil Microorganisms: Insights from Functional Metagenomics Analysis

by Seyedeh Parvin Hejazirad, Caique Menezes de Abreu, Guilherme Henrique Fernandes Carneiro, Carlos Rodrigues Gomes, Paulo Roberto de Carvalho Spinola Filho, Márcia Regina da Costa and José Barbosa dos Santos

J. Xenobiot. 2024, 14(3), 970-988; https://doi.org/10.3390/jox14030054 - 23 Jul 2024

Viewed by 847

Abstract

This study assessed the impact of phytoremediation on reducing the residual concentration of metolachlor in soil treated with doses of 530.7 and 1061.4 g/ha and its effect on microbial biodiversity in contaminated areas. For the plant species Avena sativa and Medicago sativa, [...] Read more.

This study assessed the impact of phytoremediation on reducing the residual concentration of metolachlor in soil treated with doses of 530.7 and 1061.4 g/ha and its effect on microbial biodiversity in contaminated areas. For the plant species Avena sativa and Medicago sativa, a significant efficacy of 54.5 and 36.4% was observed in the dissipation of the herbicide, especially at higher doses. Although metolachlor application reduced soil microbial biodiversity, phytoremediating plants, especially M. sativa, promoted greater richness and distribution of microbial species, mitigating the negative effects of the herbicide. Principal component analysis revealed the influence of these plants and metolachlor on the composition of the microbial community. These results highlight the importance of phytoremediation in promoting soil biodiversity and reducing herbicide contamination, providing crucial insights for remediation strategies in contaminated areas. Full article

(This article belongs to the Special Issue Plant Biostimulants - a Promising Tool in Organic Farming)

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20 pages, 7856 KiB

Open AccessArticle

Chronic Exposure to Both Electronic and Conventional Cigarettes Alters Ileum and Colon Turnover, Immune Function, and Barrier Integrity in Mice

by Madjid Djouina, Anaïs Ollivier, Christophe Waxin, Gwenola Kervoaze, Muriel Pichavant, Ségolène Caboche, Djamal Achour, Céline Grare, Delphine Beury, David Hot, Sébastien Anthérieu, Jean-Marc Lo-Guidice, Laurent Dubuquoy, David Launay, Cécile Vignal, Philippe Gosset and Mathilde Body-Malapel

J. Xenobiot. 2024, 14(3), 950-969; https://doi.org/10.3390/jox14030053 - 22 Jul 2024

Viewed by 1146

Abstract

Although the effects of cigarette smoke (CS) on the development of several intestinal diseases is well documented, the impact of e-cigarette aerosol (e-cig) on digestive health is largely unknown. To compare the effects of e-cig and CS on mouse ileum and colon, animals [...] Read more.

Although the effects of cigarette smoke (CS) on the development of several intestinal diseases is well documented, the impact of e-cigarette aerosol (e-cig) on digestive health is largely unknown. To compare the effects of e-cig and CS on mouse ileum and colon, animals were chronically exposed for 6 months by nose-only inhalation to e-cig at 18 or 30 W power, or to 3R4F CS. Results showed that e-cig exposure decreased colon cell proliferation. Several other proliferative defects were observed in response to both e-cig and CS exposure, including up- and down-regulation of cyclin D1 protein levels in the ileum and colon, respectively. E-cig and CS exposure reduced myeloperoxidase activity in the ileum. In the colon, both exposures disrupted gene expression of cytokines and T cell transcription factors. For tight junction genes, ZO-1- and occludin-protein expression levels were reduced in the ileum and colon, respectively, by e-cig and CS exposure. The 16S sequencing of microbiota showed specific mild dysbiosis, according to the type of exposure. Overall, e-cig exposure led to altered proliferation, inflammation, and barrier function in both the ileum and colon, and therefore may be a gut hazard on par with conventional CS. Full article

(This article belongs to the Topic Toxins in Medical Toxicology)

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11 pages, 2406 KiB

Open AccessCommunication

Underexplored Molecular Mechanisms of Toxicity

by Olatunbosun Arowolo and Alexander Suvorov

J. Xenobiot. 2024, 14(3), 939-949; https://doi.org/10.3390/jox14030052 - 18 Jul 2024

Viewed by 670

Abstract

Social biases may concentrate the attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in a significant [...] Read more.

Social biases may concentrate the attention of researchers on a small number of well-known molecules/mechanisms leaving others underexplored. In accordance with this view, central to mechanistic toxicology is a narrow range of molecular pathways that are assumed to be involved in a significant part of the responses to toxicity. It is unclear, however, if there are other molecular mechanisms which play an important role in toxicity events but are overlooked by toxicology. To identify overlooked genes sensitive to chemical exposures, we used publicly available databases. First, we used data on the published chemical–gene interactions for 17,338 genes to estimate their sensitivity to chemical exposures. Next, we extracted data on publication numbers per gene for 19,243 human genes from the Find My Understudied Genes database. Thresholds were applied to both datasets using our algorithm to identify chemically sensitive and chemically insensitive genes and well-studied and underexplored genes. A total of 1110 underexplored genes highly sensitive to chemical exposures were used in GSEA and Shiny GO analyses to identify enriched biological categories. The metabolism of fatty acids, amino acids, and glucose were identified as underexplored molecular mechanisms sensitive to chemical exposures. These findings suggest that future effort is needed to uncover the role of xenobiotics in the current epidemics of metabolic diseases. Full article

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16 pages, 6113 KiB

Open AccessArticle

Toxic Effects of Carbaryl Exposure on Juvenile Asian Seabass (Lates calcarifer)

by Junhua Huang, Zhengyi Fu, Wei Yu, Zemin Bai and Zhenhua Ma

J. Xenobiot. 2024, 14(3), 923-938; https://doi.org/10.3390/jox14030051 - 10 Jul 2024

Cited by 1 | Viewed by 800

Abstract

This study examines the physiological and immunological effects of 0.5 ppm carbaryl exposure on juvenile Asian seabass (Lates calcarifer) over 12 h to 72 h. Notable results include decreased activities of liver enzymes catalase (CAT), lactate dehydrogenase (LDH), and glutathione peroxidase [...] Read more.

This study examines the physiological and immunological effects of 0.5 ppm carbaryl exposure on juvenile Asian seabass (Lates calcarifer) over 12 h to 72 h. Notable results include decreased activities of liver enzymes catalase (CAT), lactate dehydrogenase (LDH), and glutathione peroxidase (GSH-PX), while superoxide dismutase (SOD) levels remained stable, with the lowest activities of CAT and GSH-PX observed at 72 h. Serum biochemistry revealed increased alkaline phosphatase (AKP) and acid phosphatase (ACP) at 24 h, with declining aspartate aminotransferase (AST) and a peak in creatinine at 48 h. Histopathological analysis showed carbaryl-induced necrosis in liver and spleen cells, and increased melanomacrophage centers in both organs. Additionally, immune gene expression analysis indicated an upregulation of heat shock proteins and consistent elevation of complement component C3 and interleukin-8 (IL-8). These findings suggest that carbaryl exposure significantly impairs organ function and modulates immune responses in L. calcarifer, underlining the need for further research on protective strategies against pesticide impacts in aquaculture. Full article

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16 pages, 1782 KiB

Open AccessArticle

Ionic Liquid 1-Octyl-3-Methylimidazolium (M8OI) Is Mono-Oxygenated by CYP3A4 and CYP3A5 in Adult Human Liver

by Alistair C. Leitch, Tarek M. Abdelghany, Alex Charlton, Martin Cooke and Matthew C. Wright

J. Xenobiot. 2024, 14(3), 907-922; https://doi.org/10.3390/jox14030050 - 9 Jul 2024

Cited by 1 | Viewed by 968

Abstract

Environmental sampling around a landfill site in the UK previously identified the methylimidazolium ionic liquid, 1-octyl-3-methylimidazolium (M8OI), in the soil. More recently, M8OI was shown to be detectable in sera from 5/20 PBC patients and 1/10 controls and to be oxidised on the [...] Read more.

Environmental sampling around a landfill site in the UK previously identified the methylimidazolium ionic liquid, 1-octyl-3-methylimidazolium (M8OI), in the soil. More recently, M8OI was shown to be detectable in sera from 5/20 PBC patients and 1/10 controls and to be oxidised on the alkyl chain in the human liver. The objective of this study was to examine the metabolism of M8OI in humans in more detail. In human hepatocytes, M8OI was mono-oxygenated to 1-(8-Hydroxyoctyl)-3-methyl-imidazolium (HO8IM) then further oxidised to 1-(7-carboxyheptyl)-3-methyl-1H-imidazol-3-ium (COOH7IM). The addition of ketoconazole—in contrast to a range of other cytochrome P450 inhibitors—blocked M8OI metabolism, suggesting primarily CYP3A-dependent mono-oxygenation of M8OI. Hepatocytes from one donor produced negligible and low levels of HO8IM and COOH7IM, respectively, on incubation with M8OI, when compared to hepatocytes from other donors. This donor had undetectable levels of CYP3A4 protein and low CYP3A enzyme activity. Transcript expression levels for other adult CYP3A isoforms—CYP3A5 and CYP3A43—suggest that a lack of CYP3A4 accounted primarily for this donor’s low rate of M8OI oxidation. Insect cell (supersome) expression of various human CYPs identified CYP3A4 as the most active CYP mediating M8OI mono-oxygenation, followed by CYP3A5. HO8IM and COOH7IM were not toxic to human hepatocytes, in contrast to M8OI, and using a pooled preparation of human hepatocytes from five donors, ketoconazole potentiated M8OI toxicity. These data demonstrate that CYP3A initiates the mono-oxygenation and detoxification of M8OI in adult human livers and that CYP3A4 likely plays a major role in this process. Full article

(This article belongs to the Section Emerging Chemicals)

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14 pages, 1790 KiB

Open AccessArticle

Contamination Profiles of Selected Pollutants in Procambarus clarkii Non-Edible Portions Highlight Their Potential Exploitation Applications

by Dario Savoca, Mirella Vazzana, Vincenzo Arizza, Antonella Maccotta, Santino Orecchio, Francesco Longo, Vittoria Giudice, Gaetano D’Oca, Salvatore Messina, Federico Marrone and Manuela Mauro

J. Xenobiot. 2024, 14(3), 893-906; https://doi.org/10.3390/jox14030049 - 6 Jul 2024

Cited by 1 | Viewed by 1165

Abstract

Properly managing aquatic organisms is crucial, including protecting endemic species and controlling invasive species. From a circular economy perspective, the sustainable use of aquatic species as a source of bioactive molecules is an area that is increasingly being explored. This includes the use [...] Read more.

Properly managing aquatic organisms is crucial, including protecting endemic species and controlling invasive species. From a circular economy perspective, the sustainable use of aquatic species as a source of bioactive molecules is an area that is increasingly being explored. This includes the use of non-edible portions of seafood, which could pose considerable risks to the environment due to current methods of disposal. Therefore, it is of paramount importance to ensure that the exploitation of these resources does not result in the transfer of pollutants to the final product. This study analyzed two types of non-edible parts from the crayfish Procambarus clarkii: the abdominal portion of the exoskeleton (AbE) and the whole exoskeleton (WE), including the cephalothorax. These portions could potentially be utilized in the context of eradication activities regulated by local authorities. A screening analysis of four classes of pollutants, including pesticides, per- and polyfluoroalkyl substances (PFAS), phthalic acid esters (PAEs), and trace elements (TEs), was performed. The only analytes detected were TEs, and significant differences in the contamination profile were found between AbE and WE. Nevertheless, the levels recorded were comparable to or lower than those reported in the literature and below the maximum levels allowed in the current European legislation for food, suggesting that their potential use is legally permitted. In terms of scalability, the utilization of the entire non-edible P. clarkii portion would represent a sustainable solution for the reuse of waste products. Full article

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20 pages, 1319 KiB

Open AccessArticle

Temporal Analysis of Pharmaceuticals as Emerging Contaminants in Surface Water and Wastewater Samples: A Case Study

by Paula Paíga, Luísa Correia-Sá, Manuela Correia, Sónia Figueiredo, Joana Vieira, Sandra Jorge, Jaime Gabriel Silva and Cristina Delerue-Matos

J. Xenobiot. 2024, 14(3), 873-892; https://doi.org/10.3390/jox14030048 - 3 Jul 2024

Cited by 1 | Viewed by 2471

Abstract

Pharmaceuticals in the environment are a global concern, with studies in all continents highlighting their widespread occurrence and potential ecological impacts, revealing their presence, fate, and associated risks in aquatic ecosystems. Despite typically occurring at low concentrations (ranging from ng/L to µg/L), advancements [...] Read more.

Pharmaceuticals in the environment are a global concern, with studies in all continents highlighting their widespread occurrence and potential ecological impacts, revealing their presence, fate, and associated risks in aquatic ecosystems. Despite typically occurring at low concentrations (ranging from ng/L to µg/L), advancements in analytical methods and more sensitive equipment have enabled the detection of a higher number of pharmaceuticals. In this study, surface and wastewater samples were extracted using solid phase extraction and analyzed using ultra-high-performance liquid chromatography with tandem mass spectrometry. Among the therapeutic classes investigated, nonsteroidal anti-inflammatory drugs/analgesics, antibiotics, and psychiatric drugs showed a higher number of detected pharmaceuticals. Concentrations ranged from below method detection limit (<MDL) to 3.20 µg/L (caffeine) and <MDL to 639 µg/L (hydroxyibuprofen) in 2018, and from <MDL to 0.848 µg/L (diclofenac) and <MDL to 53.0 µg/L (caffeine) in 2019 for river water and wastewater samples. Temporal analysis showed an increase in the sum of pharmaceutical concentrations over the study years, highlighting the importance of monitoring pharmaceuticals in the environment and their potential accumulation over time. Full article

(This article belongs to the Special Issue Pharmaceuticals and Personal Care Products: From Exposure to Impacts on Human, Animal and Ecosystem Health towards an Integrated One Health Approach)

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46 pages, 5926 KiB

Open AccessEditor’s ChoiceReview

Precision Nanomedicine with Bio-Inspired Nanosystems: Recent Trends and Challenges in Mesenchymal Stem Cells Membrane-Coated Bioengineered Nanocarriers in Targeted Nanotherapeutics

by Mirza Salman Baig, Anas Ahmad, Rijawan Rajjak Pathan and Rakesh Kumar Mishra

J. Xenobiot. 2024, 14(3), 827-872; https://doi.org/10.3390/jox14030047 - 24 Jun 2024

Cited by 2 | Viewed by 1815

Abstract

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and [...] Read more.

In the recent past, the formulation and development of nanocarriers has been elaborated into the broader fields and opened various avenues in their preclinical and clinical applications. In particular, the cellular membrane-based nanoformulations have been formulated to surpass and surmount the limitations and restrictions associated with naïve or free forms of therapeutic compounds and circumvent various physicochemical and immunological barriers including but not limited to systemic barriers, microenvironmental roadblocks, and other cellular or subcellular hinderances—which are quite heterogeneous throughout the diseases and patient cohorts. These limitations in drug delivery have been overcome through mesenchymal cells membrane-based precision therapeutics, where these interventions have led to the significant enhancements in therapeutic efficacies. However, the formulation and development of nanocarriers still focuses on optimization of drug delivery paradigms with a one-size-fits-all resolutions. As mesenchymal stem cell membrane-based nanocarriers have been engineered in highly diversified fashions, these are being optimized for delivering the drug payloads in more and better personalized modes, entering the arena of precision as well as personalized nanomedicine. In this Review, we have included some of the advanced nanocarriers which have been designed and been utilized in both the non-personalized as well as precision applicability which can be employed for the improvements in precision nanotherapeutics. In the present report, authors have focused on various other aspects of the advancements in stem cells membrane-based nanoparticle conceptions which can surmount several roadblocks and barriers in drug delivery and nanomedicine. It has been suggested that well-informed designing of these nanocarriers will lead to appreciable improvements in the therapeutic efficacy in therapeutic payload delivery applications. These approaches will also enable the tailored and customized designs of MSC-based nanocarriers for personalized therapeutic applications, and finally amending the patient outcomes. Full article

(This article belongs to the Section Drug Therapeutics)

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