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Waseem Siddiqui

Abstract: Syntheses of a small library of hydroxamates by reacting esters of different carboxylic acids with hydroxyl amine hydrochloride has been achieved. All the synthesized compounds were screened in vitro against Trypanosoma brucei... more
Abstract: Syntheses of a small library of hydroxamates by reacting esters of different carboxylic acids with hydroxyl amine hydrochloride has been achieved. All the synthesized compounds were screened in vitro against Trypanosoma brucei brucei S427 and Plasmodium falciparum 3D7 strain. The IC 50 values of potent anti-trypanosomal agents ranged between 0.025-5.69 μg/mL, while these values varied in the range of 0.78 -40.89 μg/mL against P. falciparum. Five compounds with very good SI values were active against both the protozoans. Some compounds have also shown strong antifungal activities with MIC as low as 0.19 μg/mL. These simple low molecular weight hydroxamates with triple activities and high degree of SI values revealed a new strategy in malaria/HAT and fungal chemotherapy.
SUMMARYQuinine (QN) and quinidine (QND) have been commonly used as effective and affordable antimalarials for over many years. Quinine primarily is used for severe malaria treatment. However, plasmodia resistance to these drugs and poor... more
SUMMARYQuinine (QN) and quinidine (QND) have been commonly used as effective and affordable antimalarials for over many years. Quinine primarily is used for severe malaria treatment. However, plasmodia resistance to these drugs and poor patient compliance limits their administration to the patients. The declining sensitivity of the parasite to the drugs can thus be dealt with by combining with a suitable partner drug. In the present study QN/QND was assessed in combination with clarithromycin (CLTR), an antibiotic of the macrolide family. In vitro interactions of these drugs with CLTR against Plasmodium falciparum (P. falciparum) have shown a synergistic response with mean sum fractional inhibitory concentrations (ΣFICs) of ⩽1 (0·85 ± 0·11 for QN + CLTR and 0·64 ± 0·09 for QND + CLTR) for all the tested combination ratios. Analysis of this combination of QN/QND with CLTR in mouse model against Plasmodium yoelii nigeriensis multi-drug resistant (P. yoelii nigeriensis MDR) showed that...
Proteins and their aggregation is significant field of research due to their association with various conformational maladies including well-known neurodegenerative diseases like Alzheimer's (AD), Parkinson's (PD), and... more
Proteins and their aggregation is significant field of research due to their association with various conformational maladies including well-known neurodegenerative diseases like Alzheimer's (AD), Parkinson's (PD), and Huntington's (HD) diseases. Amyloids despite being given negative role for decades are also believed to play a functional role in bacteria to humans. In this review, we discuss both facets of amyloid. We have shed light on AD, which is one of the most common age-related neurodegenerative disease caused by accumulation of Aβ fibrils as extracellular senile plagues. We also discuss PD caused by the aggregation and deposition of α-synuclein in form of Lewy bodies and neurites. Other amyloid-associated diseases such as HD and amyotrophic lateral sclerosis (ALS) are also discussed. We have also reviewed functional amyloids that have various biological roles in both prokaryotes and eukaryotes that includes formation of biofilm and cell attachment in bacteria to hormone storage in humans, We discuss in detail the role of Curli fibrils' in biofilm formation, chaplins in cell attachment to peptide hormones, and Pre-Melansomal Protein (PMEL) roles. The disease-related and functional amyloids are compared with regard to their structural integrity, variation in regulation, and speed of forming aggregates and elucidate how amyloids have turned from foe to friend.
In view of many complications of diabetes, kidney failure is considered as one of the main complications. The oxidative stress-induced due to persistent hyperglycemic conditions is the major cause of kidney disease. The present study was... more
In view of many complications of diabetes, kidney failure is considered as one of the main complications. The oxidative stress-induced due to persistent hyperglycemic conditions is the major cause of kidney disease. The present study was designed to explore the nephroprotective efficacy of polyherbal (PH) extract in a diabetic model induced by streptozotocin (STZ). STZ (55 mg/kg body weight, intraperitoneal) was injected in overnight fasting rats to develop the diabetic experimental model. Effect on kidney injury was evaluated by investigating biochemical and histological evidences in renal tissue after 56 days of treatment of PH extract. Results showed the high glucose level in STZ treated rats that suggested hyperglycemia persistence along with the successful establishment of nephropathy in diabetic rats with altered renal function, inflammatory cytokines level as well as oxidative and nitrosative stress. Administration of PH extract significantly improved the glycemic condition, ...
Background: Pricing of drugs plays a very important role in a developing country like India especially in the management of chronic conditions. There exists a huge price variation among the different brands of the same drug. Hence this... more
Background: Pricing of drugs plays a very important role in a developing country like India especially in the management of chronic conditions. There exists a huge price variation among the different brands of the same drug. Hence this study was planned to find out variation in prices of antipsychotic drugs marketed in India. The objective was to compare the percentage price variation and cost ratio of various formulations of oral and parenteral antipsychotic drugs available in the Indian market.Methods: Cost of oral and parenteral antipsychotic drugs available in the Indian market manufactured by different companies, in the same strength, number and dosage form was obtained from http://www.medguideindia.com. The percentage price variation and cost ratio of each formulation was calculated.Results: Among the typical group of antipsychotic drugs, Tab Haloperidol 0.25mg shows maximum price variation of 650% and a cost ratio of 7.5 followed by Tab Trifluoperazine 1mg having a price vari...
Mentally depressed breast cancer (MDBC) patients expressed estrogen receptor (ER) and 16α‑hydroxyestrone (16α‑OHE) is directly responsible for causing breast cancer (BC). This study aimed to identify whether depression in breast cancer... more
Mentally depressed breast cancer (MDBC) patients expressed estrogen receptor (ER) and 16α‑hydroxyestrone (16α‑OHE) is directly responsible for causing breast cancer (BC). This study aimed to identify whether depression in breast cancer patients enhanced the production of autoantibodies against 16α‑OHE-ER adduct in breast cancer patients. The antibodies in the serum of 65 breast cancer patients (including 35 MDBC) and 40 control subjects were screened by direct binding, inhibition enzyme-linked immunosorbent assay (ELISA), and quantitative precipitin titration. Competition ELISA was also utilized for the estimation of 16α‑OHE in the serum of 30 cancer patients. Autoantibodies from MDBC showed strong recognition to 16α‑OHE-ER in comparison to overall breast cancer patients (p < 0.05) and control subjects (p < 0.001). Although breast cancer sera showed high binding to 16α‑OHE-ER in comparison to ER (p < 0.05) or 16α‑OHE (p < 0.001), the relative affinities of autoantibodies for 16α‑OHE-ER were found to be 1.38 × 10 and 1.23 × 10 for breast cancer and MDBC patients respectively. No significant difference, either in the level of 16α‑OHE or 2‑hydroxyestrone/16α‑OHE ratio, was observed in the serum of cancer patients compared with controls, although inflammatory cytokines (IL-6, TNF-α) were significantly high in these patients. Depression in breast cancer patients augments the production of autoantibodies against 16α‑OHE-ER through the generation of inflammatory conditions. Depression in these patients increased the release of pro-inflammatory cytokines that generate more autoantibodies and show strong binding with 16α‑OHE-ER.
Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase,... more
Diabetic nephropathy (DN) is one of the leading causes of morbidity and mortality in diabetic patients that accounts for about 40% of deaths in type 2 diabetes. p38 mitogen activated protein kinase (p38 MAPK), a serine-threonine kinase, plays an important role in tissue inflammation and is known to be activated under conditions of oxidative stress and hyperglycemia. The role of p38 MAPK has been demonstrated in DN, and its inhibition has been suggested as an alternative approach in the treatment of DN. In the present study, we investigated the nephroprotective effects of an anti-inflammatory phenolic compound, gallic acid (GA, 3,4,5-trihydroxybenzoic acid), in high fat diet/streptozotocin (HFD/STZ) induce type 2 diabetic wistar albino rats. GA (25 mg/kgbw and 50 mg/kgbw, p.o.) treatment for 16 weeks post induction of diabetes led to a significant reduction in the levels of blood glucose, HbA1c, serum creatinine, blood urea nitrogen and proteinuria as well as a significant reduction in the levels of creatinine clearance. GA significantly inhibited the renal p38 MAPK and nuclear factor kappa B (N-κB) activation as well as significantly reduced the levels of renal transforming growth factor beta (TGF-β) and fibronectin. Treatment with GA resulted in a significant reduction in the serum levels of proinflammatory cytokines viz. interleukin 1 beta (IL-1β), IL-6 and tumor necrosis factor alpha (TNF-α). Moreover, GA significantly lowered renal pathology and attenuated renal oxidative stress. In cultured rat NRK 52E proximal tubular epithelial cells, GA treatment inhibited high glucose induced activation of p38 MAPK and NF-κB as well as suppressed proinflammatory cytokine synthesis. The results of the present study provide in vivo and in vitro evidences that the p38 MAPK pathway plays an important role in the pathogenesis of DN, and GA attenuates the p38 MAPK-mediated renal dysfunction in HFD/STZ induced type 2 diabetic rats.
Syntheses of a small library of hydroxamates by reacting esters of different carboxylic acids with hydroxyl amine hydrochloride has been achieved. All the synthesized compounds were screened in vitro against Trypanosoma brucei brucei S427... more
Syntheses of a small library of hydroxamates by reacting esters of different carboxylic acids with hydroxyl amine hydrochloride has been achieved. All the synthesized compounds were screened in vitro against Trypanosoma brucei brucei S427 and Plasmodium falciparum 3D7 strain. The IC 50 values of potent anti-trypanosomal agents ranged between 0.025-5.69 μg/mL, while these values varied in the range of 0.78 -40.89 μg/mL against P. falciparum. Five compounds with very good SI values were active against both the protozoans. Some compounds have also shown strong antifungal activities with MIC as low as 0.19 μg/mL. These simple low molecular weight hydroxamates with triple activities and high degree of SI values revealed a new strategy in malaria/HAT and fungal chemotherapy. Introduction Human African trypanosomiasis (HAT) and Malaria are vector-borne parasitic diseases caused by protozoans Trypanosoma brucei brucei (T.b.b) and Plasmodium falciparum (P. falciparum) respectively. Both the ...
Spirulina is a widely used health supplement and is a dietary source of C-Phycocyanin (CPC), a potent anti-oxidant. We have previously reported the neurotoxic potential of tributyltin chloride (TBTC), an environmental pollutant and potent... more
Spirulina is a widely used health supplement and is a dietary source of C-Phycocyanin (CPC), a potent anti-oxidant. We have previously reported the neurotoxic potential of tributyltin chloride (TBTC), an environmental pollutant and potent biocide. In this study, we have evaluated the protective efficacy of CPC against TBTC induced neurotoxicity. To evaluate the extent of neuroprotection offered by CPC, its efficacy was compared with the degree of protection offered by N-acetylcysteine (NAC) (a well known neuroprotective drug, taken as a positive control). Male Wistar rats (28day old) were administered with 20mg/kg TBTC (oral) and 50mg/kg CPC or 50mg/kg NAC (i.p.), alone or in combination, and various parameters were evaluated. These include blood-brain barrier (BBB) damage; redox parameters (ROS, GSH, redox pathway associated enzymes, oxidative stress markers); inflammatory, cellular, and stress markers; apoptotic proteins and in situ cell death assay (TUNEL). We observed increased CPC availability in cortical tissue following its administration. Although BBB associated proteins like claudin-5, p-glycoprotein and ZO-1 were restored, CPC/NAC failed to protect against TBTC induced overall BBB permeability (Evans blue extravasation). Both CPC and NAC remarkably reduced oxidative stress and inflammation. NAC effectively modulated redox pathway associated enzymes whereas CPC countered ROS levels efficiently. Interestingly, CPC and NAC were equivalently capable of reducing apoptotic markers, astroglial activation and cell death. This study illustrates the various pathways involved in CPC mediated neuroprotection against this environmental neurotoxicant and highlights its capability to modulate glial cell activity.
Tributyltin (TBT), a well-known endocrine disruptor, is an omnipresent environmental pollutant and is explicitly used in many industrial applications. Previously we have shown its neurotoxic potential on cerebral cortex of male Wistar... more
Tributyltin (TBT), a well-known endocrine disruptor, is an omnipresent environmental pollutant and is explicitly used in many industrial applications. Previously we have shown its neurotoxic potential on cerebral cortex of male Wistar rats. As the effect of TBT on other brain regions is not known, we planned this study to evaluate its effect on four brain regions (cerebellum, hippocampus, hypothalamus, and striatum). Four-week-old male Wistar rats were gavaged with a single dose of TBT-chloride (TBTC) (10, 20, and 30 mg/kg) and sacrificed on days 3 and 7, respectively. Effect of TBTC on blood-brain barrier (BBB) permeability and tin (Sn) accumulation were measured. Oxidative stress indexes such as reactive oxygen species (ROS), reduced and oxidized glutathione (GSH/GSSG) ratio, lipid peroxidation, and protein carbonylation were analyzed as they play an imperative role in various neuropathological conditions. Since metal catalyzed reactions are a major source of oxidant generation, l...
Tocotrienols, members of the vitamin E family, are natural compounds found in a number of vegetable oils, wheat germ, barley and certain types of nuts and grains. Vegetable oils provide the best sources of these vitamin E forms,... more
Tocotrienols, members of the vitamin E family, are natural compounds found in a number of vegetable oils, wheat germ, barley and certain types of nuts and grains. Vegetable oils provide the best sources of these vitamin E forms, particularly palm oil and rice bran oil contain higher amounts of tocotrienols. Other sources of tocotrienols include grape fruit seed oil, oats, hazelnuts, maize, olive oil, buckthorn berry, rye, flax seed oil, poppy seed oil and sunflower oil. Tocotrienols are of four types, viz. alpha (α), beta (β), gamma (γ) and delta (δ). Unlike tocopherols, tocotrienols are unsaturated and possess an isoprenoid side chain. A number of researchers have developed methods for the extraction, analysis, identification and quantification of different types of vitamin E compounds. This article constitutes an in-depth review of the chemistry and extraction of the unsaturated vitamin E derivatives, tocotrienols, from various sources using different methods. This review article lists the different techniques that are used in the characterization and purification of tocotrienols such as soxhlet and solid-liquid extractions, saponification method, chromatography (thin layer, column chromatography, gas chromatography, supercritical fluid, high performance), capillary electrochromatography and mass spectrometry. Some of the methods described were able to identify one form or type while others could analyse all the analogues of tocotrienol molecules. Hence, this article will be helpful in understanding the various methods used in the characterization of this lesser known vitamin E variant.
Abstract Vitamin E is the generic term for a group of tocopherols and tocotrienols (T3). Hyperlipidemia has been known to cause progressive chronic renal dysfunction (CRD). Several investigators have reported that T3 have hypolipidemic... more
Abstract Vitamin E is the generic term for a group of tocopherols and tocotrienols (T3). Hyperlipidemia has been known to cause progressive chronic renal dysfunction (CRD). Several investigators have reported that T3 have hypolipidemic and nephroprotective activity against free radical-related diseases. This study was conducted to determine if T3 as tocotrienol-rich fraction (TRF) from palm oil would protect against lipid-induced CRD in rats. For the induction of atherosclerosis and hyperlipidemia, Wistar male rats were fed an atherogenic diet containing 1.25% cholesterol, 0.5% cholic acid and 21% beef tallow (42.6% calories from fat). The atherogenic diet was given for 14 weeks to induce atherosclerosis. The control rats were given normal rat chow and drug control animals treated with TRF (100 mg/kg bw; orally). The first group was taken as disease control in which the animals were left untreated and given normal rat chow for six weeks, while the second group was treated with 100 mg TRF/kg bw. Atherosclerosis and renal functions were evaluated after six weeks of TRF treatment. Feeding an atherogenic diet to rats for 14 weeks resulted in dyslipidemia and impaired renal functions with decreased glomerular filtration rate. The treatment with TRF significantly reduced dyslipidemia and inhibited the development of CRD caused by atherogenic factors. These findings show that low-dose treatment of TRF may provide significant health benefits in the prevention of lipid-induced CRD. The study suggests that TRF is effective in preventing lipid-induced CRD.
Despite a tremendous advancement in the management of diabetes mellitus, diabetic nephropathy (DN) is still a significant problem for many patients with diabetes, because of the inefficacy and associated side effects of pharmacological... more
Despite a tremendous advancement in the management of diabetes mellitus, diabetic nephropathy (DN) is still a significant problem for many patients with diabetes, because of the inefficacy and associated side effects of pharmacological drugs. There is a demand for new therapeutic drugs which on one hand efficiently prevent the development of DN by targeting several metabolic and inflammatory pathways, and on the other hand, are side-effect free. In recent years, many researchers have suggested that inflammation plays an important role in the development of DN, hence, NF-κB has received much attention. We investigated the nephroptotective effects of baicalein (BAC), a flavonoid, in high fat diet/streptozotocin induced type 2 diabetic Wistar rats. BAC (10 mg/kg bw/day and 20 mg/kg bw/day) treatment was given to the diabetic rats by oral gavage for 16 weeks post induction of diabetes. The effect of BAC was compared to a commercial antidiabetic drug rosiglitazone (RZ, 3 mg/kg bw/day). BAC and RZ treatment significantly lowered food intake, body weight and levels of fasting blood glucose, HbA1c and homeostasis model assessment index (HOMA-IR) in diabetic rats. Both, BAC and RZ restored normal renal function and mitigated renal oxidative stress. BAC and RZ also suppressed the activation of NF-κB, decreased expression of iNOS and TGF-β1, and ameliorated the structural changes in renal tissues. Moreover, BAC also normalized the levels of serum pro-inflammatory cytokines and liver function enzymes. However, rosiglitazone treatment produced liver toxicity as was evident from increased serum levels of liver function enzymes; ALP, SGOT and SGPT. Taken together, BAC treatment preserved renal function by anti-hyperglycemic, antioxidant and anti-inflammatory effects. Moreover, BAC was found to be more effective as compared to RZ, suggesting the efficacy of BAC in the treatment of DN.
Prohibitin (PHB1) is highly conserved and ubiquitously expressed protein. It is mapped to the chromosome 17q12-q21 locus, a region that has been reported to be genetically linked to early onset of breast cancer. Therefore, we carried out... more
Prohibitin (PHB1) is highly conserved and ubiquitously expressed protein. It is mapped to the chromosome 17q12-q21 locus, a region that has been reported to be genetically linked to early onset of breast cancer. Therefore, we carried out the population-based study in a total of 105 Indian female breast cancer cases and analyzed mutation(s) on exon 4 and the introns flanking it. Importantly, it has been found that the region of this exon has specific binding site for Rb and p53 gene. We further did protein expression of Prohibitin through immunohistochemistry in the same set of population where mutation has already been found. Out of 105 breast cancer cases, 46 cases (46/105, 43.8 %) showed low or no expression (+), 19 cases (19/105, 18.0 %) with moderate (++) expression and 40 cases (40/105, 38.0 %) had high (+++) expression for Prohibitin. Highly significant association was observed statistically between Prohibitin protein expression and clinico-pathological variables like nodal status (p = 0.0003), tumor stage (p = 0.0001), histological grade (p = 0.009). Moreover, the previously found mutation(s) when analyzed with the immunohistochemistry data revealed that all the breast cancer cases with mutation representing intron deletion (deletion of T nucleotide) near the intron-exon boundary had low (+) or no expression for Prohibitin. In summary, Prohibitin may be associated with breast cancer and its down expression can serve as a potential biomarker for the effective assessment of the disease.
Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the... more
Diabetic nepropathy (DN) is considered as the leading cause of end-stage renal disease (ESRD) worldwide, but the current available treatments are limited. Recent experimental evidences support the role of chronic microinflammation in the development of DN. Therefore, the tumor necrosis factor-alpha (TNF-α) pathway has emerged as a new therapeutic target for the treatment of DN. We investigated the nephroprotective effects of chrysin (5, 7-dihydroxyflavone) in a high fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic Wistar albino rat model. Chrysin is a potent anti-inflammatory compound that is abundantly found in plant extracts, honey and bee propolis. The treatment with chrysin for 16weeks post induction of diabetes significantly abrogated renal dysfunction and oxidative stress. Chrysin treatment considerably reduced renal TNF-α expression and inhibited the nuclear transcription factor-kappa B (NF-кB) activation. Furthermore, chrysin treatment improved renal pathology and suppressed transforming growth factor-beta (TGF-β), fibronectin and collagen-IV protein expressions in renal tissues. Chrysin also significantly reduced the serum levels of pro-inflammatory cytokines, interleukin-1beta (IL-1β) and IL-6. Moreover, there were no appreciable differences in fasting blood glucose and serum insulin levels between the chrysin treated groups compared to the HFD/STZ-treated group. Hence, our results suggest that chrysin prevents the development of DN in HFD/STZ-induced type 2 diabetic rats through anti-inflammatory effects in the kidney by specifically targeting the TNF-α pathway.
Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2).... more
Apoptosis is a critically important biological process that plays an essential role in cell fate and homeostasis. An important component of the apoptotic pathway is the family of proteins commonly known as the B cell lymphoma-2 (Bcl-2). The primary role of Bcl-2 family members is the regulation of apoptosis. Although the structure of Bcl-2 family of proteins was reported nearly 10 years ago, however, it still surprises us with its structural and functional complexity and diversity. A number of studies have demonstrated that Bcl-2 family influences many other cellular processes beyond apoptosis which are generally independent of the regulation of apoptosis, suggesting additional roles for Bcl-2. The disruption of the regulation of apoptosis is a causative event in many diseases. Since the Bcl-2 family of proteins is the key regulator of apoptosis, the abnormalities in its function have been implicated in many diseases including cancer, neurodegenerative disorders, ischemia and autoimmune diseases. In the past few years, our understanding of the mechanism of action of Bcl-2 family of proteins and its implications in various pathological conditions has enhanced significantly. The focus of this review is to summarize the current knowledge on the structure and function of Bcl-2 family of proteins in apoptotic cellular processes. A number of drugs have been developed in the past few years that target different Bcl-2 members. The role of Bcl-2 proteins in the pathogenesis of various diseases and their pharmacological significance as effective molecular therapeutic targets is also discussed.
Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore,... more
Tributyltin (TBT), a member of the organotin family, is primarily used for its biocidal activity. Persistent environmental levels of TBT pose threat to the ecosystem. Since neurotoxic influence of TBT remains elusive, we therefore, studied its effect on cerebral cortex of male Wistar rats. A single oral dose of Tributyltin-Chloride (TBTC) (10, 20, 30mg/kg) was administered and the animals were sacrificed on day 3 and day 7. Blood-brain barrier permeability remained disrupted significantly till day 7 with all the doses of TBTC. Pro-oxidant metal levels (Fe, Cu) were increased with a concomitant decrease in Zn. ROS generation was substantially raised resulting in oxidative damage (increased protein carbonylation and lipid peroxidation) with marked decline in tissue antioxidant status (GSH/GSSG levels). Protein expression studies indicated astrocyte activation, upregulation of inflammatory molecules (IL-6, Cox-2 and NF-κB) and simultaneous elevation in the apoptotic index (Bax/Bcl2). Neurodegeneration was evident by reduced neurofilament expression and increased calpain cleaved Tau levels. The in-vitro study demonstrated involvement of calcium and signaling molecules (p38), with downstream activation of caspase-3 and -8, and apoptotic cell death was evident by nuclear fragmentation, DNA laddering and Annexin V binding experiments. Ca(2+) inhibitors (BAPTA-AM, EGTA, and RR) and free radical scavengers (NAC and biliprotein [C-PC]) increased cell viability (MTT assay), signifying specific roles of Ca(2+) and ROS. Significance of p38 signaling was evaluated on pro-apoptotic proteins by using SB203580, a selective p38 inhibitor. Our data collectively illustrates that TBTC can disrupt BBB, induce oxidative stress, cause cell death and initiate neurodegeneration in rat brain.
Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Free radical generation appears to be the mode of lead toxicity. We evaluated the effects of blood lead levels on oxidative stress parameters in children... more
Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Free radical generation appears to be the mode of lead toxicity. We evaluated the effects of blood lead levels on oxidative stress parameters in children suffering from neurological disorders. Thirty children (aged 3-12 years) with neurological disorders (cerebral palsy [n = 12], seizures [n = 11], and encephalopathy [n = 7]) were recruited in the study group. Sixty healthy children (aged 3-12 years) from similar socio-economic environments and not suffering from any chronic disease were taken as the controls. Blood lead levels and oxidant/antioxidant status were determined. Mean blood lead level was significantly higher while delta-aminolevulinic acid dehydratase (delta-ALAD) activity, a biomarker for lead exposure, was significantly lower in the study group as compared to the control group (P < 0.05 for each). Malondialdehyde (MDA) levels, an end-product of lipid peroxidation, were significantly higher while the antioxidant glutathione (GSH) levels were significantly lower in the study group as compared to the control group (P < 0.05 for each). Activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were significantly higher in the study group than those of the control group (P < 0.05 for each). There were significant negative correlations of blood lead levels with delta-ALAD (r = -0.35; P < 0.05) and GSH (r = -0.31; P < 0.05), and positive correlations with MDA (r = 0.37; P < 0.05), SOD (r = 0.53; P < 0.05), and CAT (r = 0.31; P < 0.05). In turn, delta-ALAD had significant negative correlations with MDA (r = -0.29; P < 0.05), SOD (r = -0.28; P < 0.05) and CAT (r = -0.34; P < 0.05), but positive correlation with GSH (r = 0.32; P < 0.05). Although a causal pathway can not be determined from the present study, our findings indicate lead-induced oxidative stress in blood of children with neurological disorders. Lead-induced oxidative stress as an underlying mechanism for neurological diseases in children warranted further investigation.
A number of experimental and clinical findings have consistently demonstrated the protective effects of Pycnogenol (PYC) in the management of diabetes. However, the protective mechanism by which PYC provides protection in a model type I... more
A number of experimental and clinical findings have consistently demonstrated the protective effects of Pycnogenol (PYC) in the management of diabetes. However, the protective mechanism by which PYC provides protection in a model type I diabetes has not been studied. This study examines the beneficial effect of PYC on hyperglycemia, inflammatory markers, and oxidative damage in diabetic rats. We also evaluated the possible mechanism of action of PYC which might be that it stimulates beta islet expression, which has been implicated in the process of insulin secretion and diabetes management. Diabetes was induced in rats by an intraperitoneal injection of streptozotocin (STZ; 60 mg/kg body weight) followed by free access to 5 % glucose for the next 24 h. Four days after STZ injection, rats were supplemented with PYC (10 mg/kg body weight) for 4 weeks. At the end of the experiment, blood was drawn, and rats were then sacrificed, and their livers and pancreases were dissected for biochemical and histological assays. The level of fasting blood glucose and glycosylated hemoglobin significantly increased but amylase, insulin, and hepatic glycogen level decreased in the STZ group. PYC significantly augmented these effects in STZ + PYC group. The STZ group showed elevated level of nitric oxide, tumor necrosis factor-α, and interleukin-1beta in serum which were decreased by PYC treatment. Moreover, PYC significantly ameliorated increased thiobarbituric reactive substances, protein carbonyl, and decreased levels of glutathione, glutathione-s-transferase, and catalase activity in the liver and pancreas of the STZ rats. Histopathological and immunohistochemical examination also revealed a remarkable protective effect of PYC. The study suggests that PYC is effective in reducing diabetic-related complications in a type I model of diabetes and might be beneficial for the treatment of diabetic patients.
Abstract: Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Free radical generation appears to be the mode of lead toxicity. We evaluated the effects of blood lead levels on oxidative stress parameters... more
Abstract: Oxidative stress plays a pivotal role in the pathogenesis of neurological disorders. Free radical generation appears to be the mode of lead toxicity. We evaluated the effects of blood lead levels on oxidative stress parameters in children suffering from neurological ...
Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). Experimental and clinical studies have shown the... more
Abnormal regulation of glucose and impaired carbohydrate utilization that result from a defective or deficient insulin are the key pathogenic events in type 2 diabetes mellitus (T2DM). Experimental and clinical studies have shown the antidiabtic effects of Pycnogenol ® (PYC) However, ...