Effect of hexavalent chromium on electron leakage of respiratory chain in mitochondria isolated from rat liver

Abstract

Background/Aims: In the present study, we explored reactive axygen species (ROS) production in mitochondria, the mechanism of hexavalent chromium (Cr(VI)) hepatotoxicity, and the role of protection by GSH. Methods: Intact mitochondria were isolated from rat liver tissues and mitochondrial basal respiratory rates of NADH and FADH 2 respiratory chains were determined. Mitochondria were treated with Cr(VI), GSH and several complex inhibitors. Mitochondria energized by glutamate/malate were separately or jointly treated with Rotenone (Rot), diphenyleneiodonium (DPI) and antimycinA (Ant), while mitochondria energized by succinate were separately or jointly treated with Rot, DPI thenoyltrifluoroacetone (TTFA) and Ant. Results: Cr(VI) concentration- dependently induced ROS production in the NADH and FADH 2 respiratory chain in liver mitochondria. Basal respiratory rate of the mitochondrial FADH 2 respiratory chain was significantly higher than that of NADH respiratory chain. Hepatic mitochondrial electron leakage induced by Cr(VI) from NADH respiratory chain were mainly from ubiquinone binding sites of complex I and complex III. Conclusion: Treatment with 50μM Cr(VI) enhances forward movement of electrons through FADH 2 respiratory chain and leaking through the ubiquinone binding site of complex III. Moreover, the protective effect of GSH on liver mitochondria electron leakage is through removing excess H 2 O 2 and reducing total ROS. © 2013 S. Karger AG, Basel.