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Kamada, S., Kusano, H., Fujita, H., Ohtsu, M., Koya, R.C., Kuzumaki, N. and Tsujimoto, Y. (1998) A cloning method for caspase substrates that uses the yeast two-hybrid system: Cloning of the antiapoptotic gene gelsolin. Proceedings of the National Academy of Sciences of the United States of America, 95, 8532-8537. doi:10.1073/pnas.95.15.8532

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

  AUTHORS: Mir-Jamal Hosseini, Nina Seyedrazi, Jafar Shahraki, Jalal Pourahmad

  KEYWORDS: Vanadium (V5+); Oxidative Stress; Glutathione Activation; Mitochondrial/Lysosomal Cross-Talk; Hepatotoxicity

  JOURNAL NAME: Advances in Bioscience and Biotechnology, Vol.3 No.8, December 12, 2012

  ABSTRACT: 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.