Hepatotoxicity and oxidative stress induced by Naja haje crude venom

Abstract

BackgroundSnake 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.MethodsWistar 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.ResultsN. 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.ConclusionsBased 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.

Elevated nitric oxide levels associated with hepatic cell apoptosis during liver injury

“…Furthermore, cobra venom or liver I/R injury (70% I/R 45 min) was reported to increase NO content in hepatic cells and enhance myeloperoxidase (MPO) activity, which were relevant to liver cell apoptosis. In the experiment of NO‐mediated HSC apoptosis, ROS and NO levels in liver cells were observed to increase greatly, accelerating cell apoptosis …”

The Venom of Spectacled Cobra (Elapidae:Naja naja):In VitroStudy from Distinct Geographical Origins in Sri Lanka

“…Several studies with similar histopathology in mice tissues suggest that the potent toxic effect of nonenzymatic fraction of cytotoxins and phospholipase A 2 (PLA 2 ) enzyme leads to these extensive necrotic observations in venom affected tissues by the formation of pores and disturbing the phospholipid structure of lipid bilayer [ 12 , 16 , 54 , 55 ]. Other research reports state similar haemorrhages and congestion in several tissue types as haemostatic disturbances produced by N. naja venom components of metalloproteinases and PLA 2 [ 13 , 35 , 56 ]. Therefore, we can conclude that venom of Sri Lankan N. naja contains functionally similar components proceeding to damage the vessel endothelium and extracellular matrix causing blood leakage into tissues.…”

“…All the vital organs and the skeletal muscle tissues acquired from the envenomed five regional mice groups demonstrated the basic defensive response of severe inflammatory cell infiltration, a reaction identified as a primary tissue activity of envenomed animals against the injurious effects of PLA 2 and PLA 2 generated reactive oxygen species of cobra venom [ 35 , 56 , 57 ]. A study on Indian N. naja found with similar leukocyte recruitment in tissues documents that PLA 2 content in cobra venom varies according to their geographical location and this automatically changes the ability of attracting inflammatory cells [ 35 ].…”

Envenoming by Viridovipera stejnegeri snake: a patient with liver cirrhosis presenting disruption of hemostatic balance

“…Stable liver cirrhosis may maintain rebalanced hemostasis because both procoagulant factors and fibrinolytic proteins are deficient [ 15 ]. An unstable hemostatic balance can be disrupted by acute phase reaction, such as infection and inflammation, and oxidative stress induced by the venom [ 12 , 13 , 16 , 17 ].…”