Selective toxicity of Caspian cobra (Naja oxiana)venom on liver cancer cell mitochondria

Objective:To explore the cytotoxicity effects of Caspian cobra(Naja oxiana or N.oxiana) venom on hepatocytes and mitochondria obtained from the liver of HCC rats.Methods:In this study,HCC was induced by diethylnitrosamine(DEN),as an initiator,and 2-acetylaminofluorene(2-AAF),as a promoter.Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effect of N.oxiana venom were isolated and mitochondria and cellular parameters related to apoptosis signaling were then determined.Results:Our results showed a raise in mitochondrial reactive oxygen species(ROS)level,swelling in mitochondria,mitochondrial membrane potential(Djm) collapse and release of cytochrome c after exposure of mitochondria only isolated from the HCC group with the crude venom of the N.oxiana(12.5,25,and 50 mg/m L).This crude venom also induced caspase-3 activation(P < 0.001) in the hepatocytes obtained only from the HCC rat liver.Conclusions:Based on the over all results,we suggested that N.oxiana may be considered as a promising complementary therapeutic agent for the treatment of HCC.

Vanadium induces liver toxicity through reductive activation by glutathione and mitochondrial dysfunction

Pentavalent vanadium (V5+) (metavanadate salt) tox- icity is a challenging problem to the health professionals and has been recognized as an industrial hazard that adversely affects human and animal health, but its cytotoxic mechanisms have not yet been completely understood. In this study, we investigated the cytotoxic mechanisms of V5+ in freshly isolated rat hepatocytes. V5+ cytotoxicity was associated with reactive oxygen species (ROS) formation, collapse of mitochondrial membrane potential, lysosomal membrane rupture and cytochrome c release into the hepatocyte cytosol. All of the above mentioned V5+ -induced cytotoxicity markers were significantly (p 5+ is activated by GSH. Our findings also showed that the lysosomotropic agents prevented V5+ induced mitochondrial membrane potential collapse. On the other hand, mitochondrial MPT pore sealing agents inhibited lysosomal membrane damage caused by V5+. It can therefore be suggested that there is probably a toxic interaction (cross-talk) between mitochondrial and lysosomal oxidative stress generating systems, which potentiates ROS formation and further damages both sub-organelles in V5+-induced induced hepatotoxicity. In conclusion, V5+-induced cytotoxicity can be attributed to oxidative stress started from glutathione mediated metal reductive activation and continued by mitochondrial/lysosomal toxic interaction.