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

Advances in Bioscience and Biotechnology 2012年第8期3卷 1096-1103页

作者： Mir-Jamal Hosseini Nina Seyedrazi jafar shahraki Jalal Pourahmad Department of Food Science and Engineering Faculty of Biosystem Engineering College of Agriculture University of Tehran Tehran Iran Faculty of Pharmacy Shahid Beheshti University of Medical Sciences Tehran Iran

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.

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

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

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Advances in Bioscience and Biotechnology（生命科学与技术进展） 2012年第8期

作者： Mir-Jamal Hosseini Nina Seyedrazi jafar shahraki Jalal Pourahmad

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