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Effect of the Montivipera bornmuelleri snake venom on human blood: coagulation disorders and hemolytic activities
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Skeletal muscle is composed of multinucleated, mature muscle cells (myofibers) responsible for contraction, and a resident pool of mononucleated muscle cell precursors (MCPs), that are maintained in a quiescent state in homeostatic... more
Skeletal muscle is composed of multinucleated, mature muscle cells (myofibers) responsible for contraction, and a resident pool of mononucleated muscle cell precursors (MCPs), that are maintained in a quiescent state in homeostatic conditions. Skeletal muscle is remarkable in its ability to adapt to mechanical constraints, a property referred as muscle plasticity and mediated by both MCPs and myofibers. An emerging body of literature supports the notion that muscle plasticity is critically dependent upon nuclear mechanotransduction, which is transduction of exterior physical forces into the nucleus to generate a biological response. Mechanical loading induces nuclear deformation, changes in the nuclear lamina organization, chromatin condensation state, and cell signaling, which ultimately impacts myogenic cell fate decisions. This review summarizes contemporary insights into the mechanisms underlying nuclear force transmission in MCPs and myofibers. We discuss how the cytoskeleton a...
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Skeletal muscle is composed of multinucleated, mature muscle cells (myofibers) responsible for contraction, and a resident pool of mononucleated muscle cell precursors (MCPs), that are maintained in a quiescent state in homeostatic... more
Skeletal muscle is composed of multinucleated, mature muscle cells (myofibers) responsible for contraction, and a resident pool of mononucleated muscle cell precursors (MCPs), that are maintained in a quiescent state in homeostatic conditions. Skeletal muscle is remarkable in its ability to adapt to mechanical constraints, a property referred as muscle plasticity and mediated by both MCPs and myofibers. An emerging body of literature supports the notion that muscle plasticity is critically dependent upon nuclear mechanotransduction, which is transduction of exterior physical forces into the nucleus to generate a biological response. Mechanical loading induces nuclear deformation, changes in the nuclear lamina organization, chromatin condensation state, and cell signaling, which ultimately impacts myogenic cell fate decisions. This review summarizes contemporary insights into the mechanisms underlying nuclear force transmission in MCPs and myofibers. We discuss how the cytoskeleton a...
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Background : Genetic factors represent the major etiological contributor in Autism Spectrum Disorders (ASD) but several studies also support the involvement of environmental factors. This last hypothesis is reinforced by the evident... more
Background : Genetic factors represent the major etiological contributor in Autism Spectrum Disorders (ASD) but several studies also support the involvement of environmental factors. This last hypothesis is reinforced by the evident increase in the prevalence of this disorder in the last decades. Thus, in our study, we aimed to identify the correlation between factors related to sociodemographic elements, to child and mother’s health and ASD in order to dress a best detailed profile of the patients. Methods : We conducted a case-control study including 64 Lebanese patients with ASD and 67 matched controls recruited from all the Lebanese districts. Our data has been analyzed by SPSS 23.0 and the statistical tests carried out were the Independent Sample t-test and the Chi-Square test. In addition, a multivariate logistic regression analysis has been carried out using variables that showed a p<0.05 in the bivariate analysis. Results : Our findings suggest that consanguinity (OR=4; 9...
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Le catabolisme de l'ATP fournit aux muscles stries l'energie necessaire pour la contraction et conduit a la production d'adenosine. Cette derniere regule la contraction en agissant sur des recepteurs membranaires. Le Ca2+... more
Le catabolisme de l'ATP fournit aux muscles stries l'energie necessaire pour la contraction et conduit a la production d'adenosine. Cette derniere regule la contraction en agissant sur des recepteurs membranaires. Le Ca2+ necessaire pour la contraction des muscles squelettiques et cardiaque de mammiferes provient en partie de sa liberation du reticulum sarcoplasmique par les recepteurs a la ryanodine. Cependant, dans le muscle cardiaque, l'echangeur Na+/Ca2+ pourrait egalement participer a l'elevation de la concentration calcique intracellulaire. Le but de ce travail etait d'etudier les effets de l'adenosine sur la charge et la liberation du Ca2+ du reticulum sarcoplasmique des muscles squelettiques lent (soleaire) et rapide (edl) de rat et du muscle cardiaque de furet. Les resultats des experiences realisees sur des fibres pelees a la saponine ont montre que l'adenosine n'induit aucun effet significatif sur la charge en Ca2+ du reticulum sarcopla...
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Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics therapy approaches... more
Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics therapy approaches seemed relevant. Here, we evaluated the potency of the aqueous Buds extract of Eucalyptus (ABEE) to counteract the main enzymatic activities of Montivipera bornmuelleri venom. We showed that ABEE efficiently counteracts the proteolytic, Phospholipases A2 (PLA2), and L-aminoacid oxidase activities (LAAO) of M. bornmuelleri venom. ABEE was found to inhibit Acetylcholine esterase (AChE) and to exhibit a potent antioxidant activity. In addition, M. bornmuelleri venom displays antibacterial properties against Staphylococcus aureus, which were not inhibited by ABEE. We also showed that of M. bornmuelleri venom lacks AChE, either anti-AChE activities. ABEE represents a promising natural source of antivenomics compounds against the deleterious effects of M...
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Kossaifi, E. Hraoui-Bloquet, S. Sadek, R. Fajloun, Z. Accary, C. and Hleihel. W. 2017. Histological alterations in Kidney and Liver of laboratory mice following intramuscular injection of Montevipera bornmuelleri (Werner, 1898) Venom.... more
Kossaifi, E. Hraoui-Bloquet, S. Sadek, R. Fajloun, Z. Accary, C. and Hleihel. W. 2017. Histological alterations in Kidney and Liver of laboratory mice following intramuscular injection of Montevipera bornmuelleri (Werner, 1898) Venom. Lebanese Science Journal, 18(1): 122-135. Histopathological changes after bites of the Montivipera bornmuelleri viper, endemic to high altitudes areas of Lebanon, have not yet been investigated. Our study focuses on histological changes and irreversible damages in the kidney and liver of white laboratory Balb/c mice that received an intramuscular injection of lyophilized venom diluted in saline solution (NaCl 0.9%). Different venom concentration doses ranging from 0.25 mg/kg to 15mg/kg in a total injection volume of 100μl was injected intramuscularly (IM) into 5 groups of mice. After dissection, observations showed no macroscopically identifiable damages in any of the organs studied. However, tissue samples from the liver and the kidney were obtained f...
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Breast Cancer is one of the world’s most notorious diseases affecting two million women in 2018 worldwide. It is a highly heterogeneous disease, making it difficult to treat. However, its linear progression makes it a candidate for early... more
Breast Cancer is one of the world’s most notorious diseases affecting two million women in 2018 worldwide. It is a highly heterogeneous disease, making it difficult to treat. However, its linear progression makes it a candidate for early screening programs, and the earlier its detection the higher the chance of recovery. However, one key hurdle for breast cancer screening is the fact that most screening techniques are expensive, time-consuming, and cumbersome, making them impractical for use in several parts of the world. One current trend in breast cancer detection has pointed to a possible solution, the use of salivary breast cancer biomarkers. Saliva is an attractive medium for diagnosis because it is readily available in large quantities, easy to obtain at low cost, and contains all the biomarkers present in blood, albeit in lower quantities. Affinity sensors are devices that detect molecules through their interactions with biological recognition molecules. Their low cost, high ...
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We analyzed for the first time the metabolic profile of Lebanese children affected by autistic disorders to compare this profile to other metabolomics studies and to identify the associated metabolic disturbances. Urine samples of 40... more
We analyzed for the first time the metabolic profile of Lebanese children affected by autistic disorders to compare this profile to other metabolomics studies and to identify the associated metabolic disturbances. Urine samples of 40 patients with Autism spectrum disorder (ASD) and 40 healthy matched controls were analyzed using nuclear magnetic resonance (NMR) and liquid chromatography coupled to high-resolution mass spectrometry (LC-MS). Multivariate analysis on analytical data fusion was conducted on the training set of 50 urine samples, and then validated with a test set of 30 samples, this repeated 10 times. The model was also evaluated using a receiver operating characteristic curve showing a specificity and a sensitivity of 86% and 80%, respectively. Among the most significant metabolites that contributed to the discrimination between ASD and controls, we confirmed the perturbations of tyrosine, 2-hydroxybutyrate, creatine and glutamate. We found new metabolites such as trigo...
Research Interests: Chemistry, Analytical Chemistry, Metabolomics, Oxidative Stress, Magnetic Resonance Spectroscopy, and 15 moreMedicine, Humans, Child, Female, Male, ROC Curve, Autism Spectrum Disorder, High Pressure Liquid Chromatography, Amino Acids, Carbohydrate metabolism, Sensitivity and Specificity, Metabolome, Case Control Studies, Autistic disorder, and Pharmacology and pharmaceutical sciences
Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics therapy approaches... more
Because snake venoms are complex mixtures of bioactive molecules, snake bites produce a large panel of symptoms which cannot be totally prevented by current antivenoms. Thus investigating plant extracts for antivenomics therapy approaches seemed relevant. Here, we evaluated the potency of the aqueous Buds extract of Eucalyptus (ABEE) to counteract the main enzymatic activities of Montivipera bornmuelleri venom. We showed that ABEE efficiently counteracts the proteolytic, Phospholipases A2 (PLA2), and L-aminoacid oxidase activities (LAAO) of M. bornmuelleri venom. ABEE was found to inhibit Acetylcholine esterase (AChE) and to exhibit a potent antioxidant activity. In addition, M. bornmuelleri venom displays antibacterial properties against Staphylococcus aureus, which were not inhibited by ABEE. We also showed that of M. bornmuelleri venom lacks AChE, either anti-AChE activities. ABEE represents a promising natural source of antivenomics compounds against the deleterious effects of M...
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The Viperidae family venom is a rich source of bioactive compounds such as many proteases, which cause tissue necrosis and affect mostly the vascular system. However, the venom exhibits therapeutic potentials and has contributed to the... more
The Viperidae family venom is a rich source of bioactive compounds such as many proteases, which cause tissue necrosis and affect mostly the vascular system. However, the venom exhibits therapeutic potentials and has contributed to the development of some medical drugs. Specifically, the Montivipera bornmuelleri venom has shown to exhibit antibacterial, pro-inflammatory and antifungal activities. This work evaluates the cytotoxic effect of the M. bornmuelleri venom on human-derived keratinocytes including the non-tumorigenic HaCaT, the benign A5 and the low-grade malignant II4 cells. The toxicity of different venom concentrations (0.9, 1.87, 3.75, 7.5, 15, 30 and 60μg/mL) and their effect on the viability of the cells lines were assessed using the Lactate Dehydrogenase (LDH) activity and the Trypan blue tests after 24h of incubation. The venom was able to reduce the viability of all cell lines in a dose dependent manner with the HaCat cells being the least affected. For example, the...
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Abstract: Montivipera bornmuelleri is an endangered viper that has been described as endemic to the Lebanese mountains. The lethal dose 50% (LD50) of M. bornmuelleri venom has been determined by performing intravenous, intraperitoneal... more
Abstract: Montivipera bornmuelleri is an endangered viper that has been described as endemic to the Lebanese mountains. The lethal dose 50% (LD50) of M. bornmuelleri venom has been determined by performing intravenous, intraperitoneal (IP), and subcutaneous injections. However, to date, intramuscular injection has not been performed to determine LD50, nor have the minimum hemorrhagic (MHD) or the minimum necrotic doses (MND) been evaluated. Thus, this study was conducted to complete the characterization of the M. bornmuelleri venom. Our results showed that intramuscularly injected LD50 is around 5.39 mg/kg, and IP LD50 is around 1.93 mg/kg. After intradermal injection, our findings showed significant necrotic and medium hemorrhagic activities, and MHD was around 250 µg/kg. By comparing with other local venomous snakes, these results indicate that the lethality of M. bornmuelleri venom is similar to that of Daboia palaestinae venom (IP LD50=1.9 mg/kg) and is higher than that of Macrovipera lebetina venom (IP LD50=7.58 mg/kg) and that the hemorrhagic activity of M. bornmuelleri venom is lower than that of the Macrovipera lebetina (MHD=200 µg/kg). On the other hand, necrotic activity was detected at low doses of injected venom: MND was estimated at 20 µg/kg. Altogether, our findings could extend the scope of characterization of M. bornmuelleri venom and provide useful data for further in vivo studies.
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- This study concentrates on the Lebanon mountain viper Montivipera bornmuelleri endemic to the Lebanese mountains, in terms of ecology, geographic distribution and preliminary biochemical characterization of its venom. Here, we show that... more
- This study concentrates on the Lebanon mountain viper Montivipera bornmuelleri endemic to the Lebanese mountains, in terms of ecology, geographic distribution and preliminary biochemical characterization of its venom. Here, we show that Montivipera bornmuelleri lives in habitats dominated by a variety of mountain plant species at altitudes ranging from 1900 m to 2200 m. This viper exists in association with endemic lacertid lizards in the Oyoun Simane area of Sannine mountain and with other snakes (such as Platyceps najadum and Hemorrhois ravergieri) in the Makmel (Bcharre) mountain. - Preliminary analysis of this viper’s venom was conducted using Liquid Chromatography coupled to Electrospray Ionisation Mass Spectrometry (LC-ESI-MS). This analysis revealed the presence of some bioactive molecules in the crude product. This work constitutes a preliminary study of a research project involving the extraction and characterization of bioactive molecules and potential therapeutic uses o...
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This study concentrates on the Lebanon mountain viper Montivipera bornmuelleri endemic to the Lebanese mountains, in terms of ecology, geographic distribution and preliminary biochemical characterization of its venom. Here, one shows that... more
This study concentrates on the Lebanon mountain viper Montivipera bornmuelleri endemic to the Lebanese mountains, in terms of ecology, geographic distribution and preliminary biochemical characterization of its venom. Here, one shows that M. bornmuelleri lives in habitats dominated by a variety of mountain plant species at altitudes ranging from 1900 m to 2200 m. This viper exists in association with endemic lacertid lizards in the Oyoun Al Simane area of Kfardebian in the Sannine mountain and with other snakes (such as Platyceps najadum (Müller, 1878) and Hemorrhois ravergieri (Ménétries, 1832) in the Makmel (Bcharre) mountain. Preliminary analysis of this viper's venom was conducted using liquid chromatography coupled to electrospray ionisation mass spectrometry (LC-ESI-MS). The analysis revealed the presence of some bioactive molecules in the crude product. This work constitutes a preliminary study of a research project involving the extraction and characterization of bioacti...
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The present study performed on chemically skinned skeletal fibres was designed to compare the effects of adenosine on the Ca2+ sensitivity of contractile proteins and on caffeine-induced Ca2+ release in rat slow- (soleus) and fast-twitch... more
The present study performed on chemically skinned skeletal fibres was designed to compare the effects of adenosine on the Ca2+ sensitivity of contractile proteins and on caffeine-induced Ca2+ release in rat slow- (soleus) and fast-twitch (edl) muscles. The tension-pCa relationships were obtained by exposing triton X-100 (1% v/v) skinned fibres sequentially to solutions of decreasing pCa in the presence or in absence of adenosine. Then, changes in caffeine contracture due to adenosine were recorded on saponin (50 microg/ml) skinned fibres. The results show that the sensitivity to Ca2+ of contractile proteins in the presence of different concentrations of caffeine was not significantly modified by adenosine. However, it was proposed that adenosine (0.1-2 mM) reduced the Ca2+ released by caffeine (0.1-10 mM) from the sarcoplasmic reticulum in slow- and fast-twitch fibres and that the soleus was more sensitive to adenosine than edl muscle. The effects of specific A2a and A1 agonists and antagonists were also tested on caffeine contractures. It was found that the A1 antagonist reduced adenosine effect on caffeine response. Then it is proposed that adenosine modulates the sarcoplasmic reticulum Ca2+ release by a direct effect on the RyR1 receptors and/or by an indirect effect mediated by A1 receptors located at the sarcoplasmic level.
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The present study performed on chemically skinned skeletal fibres was designed to compare the effects of adenosine on the Ca2+ sensitivity of contractile proteins and on caffeine-induced Ca2+ release in rat slow- (soleus) and fast-twitch... more
The present study performed on chemically skinned skeletal fibres was designed to compare the effects of adenosine on the Ca2+ sensitivity of contractile proteins and on caffeine-induced Ca2+ release in rat slow- (soleus) and fast-twitch (edl) muscles. The tension-pCa relationships were obtained by exposing triton X-100 (1% v/v) skinned fibres sequentially to solutions of decreasing pCa in the presence or in absence of adenosine. Then, changes in caffeine contracture due to adenosine were recorded on saponin (50 microg/ml) skinned fibres. The results show that the sensitivity to Ca2+ of contractile proteins in the presence of different concentrations of caffeine was not significantly modified by adenosine. However, it was proposed that adenosine (0.1-2 mM) reduced the Ca2+ released by caffeine (0.1-10 mM) from the sarcoplasmic reticulum in slow- and fast-twitch fibres and that the soleus was more sensitive to adenosine than edl muscle. The effects of specific A2a and A1 agonists and antagonists were also tested on caffeine contractures. It was found that the A1 antagonist reduced adenosine effect on caffeine response. Then it is proposed that adenosine modulates the sarcoplasmic reticulum Ca2+ release by a direct effect on the RyR1 receptors and/or by an indirect effect mediated by A1 receptors located at the sarcoplasmic level.
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The aim of this study was to investigate the effects of adenosine on reverse mode Na+/Ca2+ exchange. In intact ferret cardiac trabeculae, Na+-free contractures were investigated after treating preparations with ryanodine, a sarcoplasmic... more
The aim of this study was to investigate the effects of adenosine on reverse mode Na+/Ca2+ exchange. In intact ferret cardiac trabeculae, Na+-free contractures were investigated after treating preparations with ryanodine, a sarcoplasmic reticulum Ca2+-channel inhibitor, and thapsigargin, a sarcoplasmic reticulum Ca2+-pump inhibitor added to suppress the sarcoplasmic reticulum function. The effects of adenosine (50–100 nmol/L), adenosine deaminase (ADA, 0.1–0.5 U/L), the A1 and A2A receptor agonists CCPA (3–100 nmol/L) and CGS 21680 (25–100 nmol/L), and the A1 and A2A receptor antagonists DPCPX (25 nmol/L) and ZM 241385 (25 nmol/L) were tested on Na+-free contractures. The application of adenosine (50–100 nmol/L) had no significant effect on the characteristics of the Na+-free contractures. However, the results show that treatment with ADA (0.3 U/L), adenosine (≥50 nmol/L) and CCPA, a specific A1 receptor agonist (3–100 nmol/L), all reduced the Na+-free contracture amplitude. In the ...
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Background In developing countries, brand-generic substitution is not based on validated scientific evidence that confirm the therapeutic equivalence of the generic to the originator. Rather, decisions are made based on the availability... more
Background In developing countries, brand-generic substitution is not based on validated scientific evidence that confirm the therapeutic equivalence of the generic to the originator. Rather, decisions are made based on the availability of generic medications. Substitution by inappropriate preparations applies to antibiotics, which may increase the risk of resistance in case of underdosing. This analytical study aims to dose and assess for the accuracy of labeling three oral antibiotic preparations, namely ciprofloxacin hydrochloride, amoxicillin trihydrate and amoxicillin trihydrate-clavulanate potassium, the active pharmaceutical ingredients (APIs) found in brand and generic tablets available on the Lebanese market. Methods One brand and 4 generics of ciprofloxacin tablets, 3 generic amoxicillin tablets, and 1 brand and 4 generics of amoxicillin-clavulanic acid medications, were quantified, taking 2 batches of each. According to the United States Pharmacopeia (USP) guidelines, ult...
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In our previous study, in which array CGH was used on 19 Lebanese ASD subjects and their parents, we identified rare copy number variants (CNVs) in 14 subjects. The five remaining subjects did not show any CNVs related to autism spectrum... more
In our previous study, in which array CGH was used on 19 Lebanese ASD subjects and their parents, we identified rare copy number variants (CNVs) in 14 subjects. The five remaining subjects did not show any CNVs related to autism spectrum disorders (ASD). In the present complementary study, we applied whole-exome sequencing (WES), which allows the identification of rare genetic variations such as single nucleotide variations and small insertions/deletions, to the five negative CNV subjects. After stringent filtering of initial data on the five families, three novel genes potentially related to neurodevelopment were identified, including a de novo mutation in the MIS18BP1 gene. In addition, genes already known to be related to ASD contained sequence variations. Our findings outline the potential involvement of the novel de novo mutation in the MIS18BP1 gene in the genetic etiology and pathophysiology of ASD and highlights the genetic complexity of these disorders. Further studies with...
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Autism spectrum disorders (ASD) are among the most common childhood neurodevelopmental disorders. Identification of risk and protective factors are necessary to improve the guidance of prevention and intervention strategies. Our study... more
Autism spectrum disorders (ASD) are among the most common childhood neurodevelopmental disorders. Identification of risk and protective factors are necessary to improve the guidance of prevention and intervention strategies. Our study aims to determine the potential risk and protective factors in ASD in the Lebanese population. Our case-control study included 100 ASD patients and 100 healthy matched controls recruited from all the Lebanese districts. The data collected from the questionnaires was analyzed using SPSS 23.0. Independent Student T-test and Chi-Square test were carried out for the bivariate analysis of the data. In addition, the variables revealing a p-value < 0.05 were used for the multivariate logistic regression analysis. Multivitamins intake, especially omega 3 and vitamin B (Odds Ratio (OR) = 0.257; 95% Confidence Interval (CI) [0.115–0.579]), rich cereal diet (OR = 0.212; 95% CI [0.089–0.510]), and supplementation in iron during pregnancy (OR = 0.229; 95% CI [0....
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This study concentrates on the Lebanon mountain viper Montivipera bornmuelleri endemic to the Lebanese mountains, in terms of ecology, geographic distribution and preliminary biochemical characterization of its venom. Here, one shows that... more
This study concentrates on the Lebanon mountain viper Montivipera bornmuelleri endemic to the Lebanese mountains, in terms of ecology, geographic distribution and preliminary biochemical characterization of its venom. Here, one shows that M. bornmuelleri lives in habitats dominated by a variety of mountain plant species at altitudes ranging from 1900 m to 2200 m. This viper exists in association with endemic lacertid lizards in the Oyoun Al Simane area of Kfardebian in the Sannine mountain and with other snakes (such as Platyceps najadum (Müller, 1878) and Hemorrhois ravergieri (Ménétries, 1832) in the Makmel (Bcharre) mountain. Preliminary analysis of this viper’s venom was conducted using liquid chromatography coupled to electrospray ionisation mass spectrometry (LC-ESI-MS). The analysis revealed the presence of some bioactive molecules in the crude product. This work constitutes a preliminary study of a research project involving the extraction and characterization of bioactive m...
Beside their toxicity, snake venom components possess several pharmacological effects and have been used to design many drugs. Recently, the cytotoxic, antibacterial, vasorelaxant, pro- and anti-coagulant as well as inflammatory... more
Beside their toxicity, snake venom components possess several pharmacological effects and have been used to design many drugs. Recently, the cytotoxic, antibacterial, vasorelaxant, pro- and anti-coagulant as well as inflammatory activities of venom have been described . However, the effects of this Lebanese snake venom on the immune system has not been established yet. Here, we investigate the immunomodulatory effects of venom on the murine splenic levels of TNF-α, IFN-γ, IL-4, IL-10, IL-1ß and IL-17 at 6 and 24 h post treatment. Different doses of the venom (1 mg/kg, 2 mg/kg, 4 mg/kg and 6 mg/kg) were injected intraperitoneally in BALB/c mice. Using the logit method, LD of was proved to be 1.92 mg/kg in our experimental conditions. This study also shows that 1 mg/kg and 2 mg/kg of venom are able to modulate the levels of cytokines in the spleen of mice, as assessed by ELISA. In fact, this snake's venom up-regulates TNF-α, IFN-γ, IL-1ß and IL-17 with a trend in decreasing IL-4 a...