Protective Effects of Melatonin against Oxidative Stress in Flow Cytometry-sorted Buffalo Sperm (original) (raw)
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Acta tropica, 2017
Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potent...
Journal of pineal research, 2015
Oxidative stress induced methemoglobinemia remained an untouched area in venom pharmacology till date. This study for the first time explored the potential of animal venoms to oxidize hemoglobin to methemoglobin. In in vitro whole blood assay, methemoglobin forming ability of venoms varied as, N. naja > O. hannah > E. carinatus > D. russellii > A. mellifera > M. tamulus > H. partita. Being highly potential, N. naja venom was further studied to observe methemoglobin formation in RBCs and in combinations with PMNs and PBMCs, where maximum effect was observed in RBCs + PMNs combination. N. naja venom/externally added methemoglobin induced methemoglobin formation was in parallel with ROS generation in whole blood/ RBCs/ RBCs + PMNs/ RBCs + PBMCs. In in vivo studies, the lethal dose (1 mg/kg body weight, i.p.) of N. naja venom readily induced methemoglobin formation, ROS generation, expression of inflammatory markers, and hypoxia inducible factor-3α. Although the mice a...
Andrologia, 2012
Naja haje envenomation is one of the leading causes of death due to snakebite. Antiserum therapy sometimes fails to provide enough protection against venom toxicity. In this study, we investigated the protective effects of melatonin against N. haje venom in rats. The animals were injected with venom (0.25 mg/kg) and/or melatonin (10 mg/kg) and compared with vehicle-treated rats. There was oxidative/nitrosative damage and apoptosis in the liver, heart, and kidneys of venom-injected rats. Melatonin counteracted the increased lipoperoxidation and nitric oxide, prevented decreased glutathione peroxidase and reductase activity, reduced the glutathione disulfide/glutathione (GSSG/GSH) ratio, and maintained the GSH pool. Furthermore, melatonin administration was associated with a reduction of apoptosis, which was increased in venom-injected rats. Overall, these results suggest that melatonin mitigates oxidative/nitrosative stress in venom-induced cardio-hepato-renal injury in rats. Our results suggest that melatonin treatment may ameliorate some of the effects of N. haje envenomation.
Journal of Pineal Research, 2009
Abstract: Melatonin (N-acetyl-5-methoxytryptamine) is an efficient free radical scavenger and antioxidant, both in vitro and in vivo. The role of melatonin as an immunomodulator is, in some cases, contradictory. In this study we have investigated the therapeutic efficacy of melatonin in rats subjected to Pelagia noctiluca crude venom (of the familia Pelaguiidae; and genus Pelagia) induced acute paw inflammation. In particular, injection of the venom into the paw of rats elicited an acute inflammatory response characterized by accumulation of fluid containing a large number of polymorphonuclear neutrophils in the paw and subsequent lipid peroxidation. Furthermore, the venom promoted an expression of iNOS, nitrotyrosine and the activation of the nuclear enzyme poly (ADP-ribose) polymerase as determined by immunohistochemical analysis of paw tissues. Administration of melatonin 30 min, 1 and 6 hr after the challenge with the venom, caused a significant reduction in all the parameters of inflammation measured. Thus, based on these findings we propose that melatonin may be useful a treatment of local acute inflammation induced by P. noctiluca crude venom.
Biological effects of Naja haje crude venom on the hepatic and renal tissues of mice
Journal of King Saud University - Science, 2014
Snake venoms are known to cause different metabolic disorders, altering cellular and enzymatic activities in animals and releasing pharmacological substances. In this study, the lethality as well as biochemical and histopathological effect of Egyptian cobra (Naja haje; N. haje) crude venom at a sublethal dose have been investigated on liver and kidney of male mice. Venom injected intramuscularly in mice with 1/2 LD50 (approximately 0.0115 lg/g body weight of mice) and the animals were sacrificed 6 days post injection. Results indicated that the injection of crude venom of the N. haje induced a significant disturbance in liver and kidney functions. In addition, results revealed that N. haje venom has a potent oxidative activity by increasing the level of reactive oxygen species with concomitant significant increase in hydrogen peroxide, lipid peroxidation, carbonyl protein and nitric oxide levels in hepatic and renal tissues. This activity was extended to decrease non-enzymatic and enzymatic antioxidant defense components such as glutathione, superoxide dismutase and catalase. Additionally, the biochemical alternations induced in hepatic and renal tissues were associated with significant alternations in the histological architecture of liver and kidney of injected mice. From this study, we can conclude that such injury could be considered among the * Corresponding authors. Address:
Snakebite is a serious and important problem in tropical and subtropical countries including Egypt. The venom of Egyptian cobra (Naja haje; LINNAEUS) is complex, and it has been a good source of short neurotoxins and several cytotoxins. In this study, oxidative stress inductions as well as apoptotic effects of the Egyptian cobra crude venom at a dose of 0.025mg/kg (intraperitoneal injection; i.p.) has been investigated in kidney of rats after 4 hours. Twelve rats divided into 2 groups, Group I served as control group, Group II received i.p. injection of 0.025mg/kg of crude venom. The venom enhanced lipid peroxidation and nitric oxide productions in the kidney with concomitant reduction in glutathione content and superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and glutathione-S-transferase activities were inhibited. Moreover, the venom induced a renal injury as indicated by histopathological changes in the kidney tissue with an elevation in serum creatinine and urea. In addition, the renal ultrastructural changes were in the form of blebbing of visceral epithelial cells, and foot process disorganization. Also, the glomerular capillaries lined by hypertrophied endothelial cells. These findings were associated with the pro-apoptotic action in the kidney. The results suggest that Egyptian cobra venom stimulates oxidative stress to induce apoptosis in kidney tissue through inhibition of mitochondrial respiration in male rats.
Hepatotoxicity and oxidative stress induced by Naja haje crude venom
Background Snake venoms are synthesized and stored in venom glands. Most venoms are complex mixtures of several proteins, peptides, enzymes, toxins and non-protein components. In the present study, we investigated the oxidative stress and apoptosis in rat liver cells provoked by Naja haje crude injection (LD50) after four hours. Methods Wistar rats were randomly divided into two groups, the control group was intraperitoneally injected with saline solution while LD50-dose envenomed group was intraperitoneally injected with venom at a dose of 0.025 μg/kg of body weight. Animals were killed four hours after the injection. Lipid peroxidation, nitric oxide and glutathione levels were measured as oxidative markers in serum and liver homogenate. In addition, liver function parameters and activities of antioxidant enzymes were determined. Results N. haje crude venom (0.025 μg/kg of body weight) enhanced lipid peroxidation and nitric oxide production in both serum and liver with concomitant reduction in glutathione, catalase, glutathione reductase and glutathione-S-transferase activities. Superoxide dismutase and glutathione peroxidase activities were significantly increased in liver of envenomed rats. These findings were associated with apoptosis induction in the liver. In addition, N. haje crude venom caused hepatic injury as indicated by histopathological changes in the liver tissue with an elevation in total bilirubin, serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transpeptidase, and alkaline phosphatase. Conclusions Based on the present results, it can hypothesized that N. haje crude venom is a potent inducer of toxin-mediated hepatotoxicity associated with apoptosis in the liver.
Effects of the crotalus durissus terrificus snake venom on hepatic metabolism and oxidative stress
Journal of Biochemical and Molecular Toxicology, 2011
Snake venoms present different action mechanisms because of their complex composition, represented mainly by toxins and enzymes. This work aimed to investigate the effects of the Crotalus durissus terrificus (Cdt) venom in the liver. Wistar rats were inoculated intraperitoneally with saline (control) or Cdt venom. After 3, 4, or 6 h, the following parameters were analyzed: (a) hepatic function, (b) oxidative stress parameters, and (c) the metabolism of alanine in the isolated perfused liver. Plasma activities of alanine aminotransferase and aspartate aminotransferase and hepatic glutathione S-transferase and catalase presented significant elevation in rats inoculated with 300 μg·kg −1 Cdt venom. Liver lipoperoxidation was enormously increased by venom doses of 100, 200, and 300 μg·kg −1 , whereas glutathione S-transferase was not changed. Perfused livers from rats inoculated with 1500 μg·kg −1 venom showed increased production of lactate, pyruvate, and ammonia when alanine was the metabolic substrate. These results demonstrate that the Cdt venom can produce several changes in hepatocytes. The causes of the changes are possibly related to the disequilibrium in the redox homeostasis but also to specific needs of the poisoned organism, for example, an increased supply of lactate and pyruvate in response to an increased activity of the Cori cycle. C 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 00:1-9, 2010; View this article online at wileyonlinelibrary.com.