Author(s)

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 < 0.05) prevented by ROS scavengers, antioxidants and mitochondrial permeability transition (MPT) pore sealing agents. Hepatocyte glutathione (GSH) was also rapidly oxidized and GSH-depleted hepatocytes were more resistant to lithium-induced oxidative stress markers. This suggests that V⁵⁺ 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.

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

Hosseini, M. , Seyedrazi, N. , Shahraki, J. and Pourahmad, J. (2012) Vanadium induces liver toxicity through reductive activation by glutathione and mitochondrial dysfunction. Advances in Bioscience and Biotechnology, 3, 1096-1103. doi: 10.4236/abb.2012.38134.