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 FADH₂ 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 FADH₂ respiratory chain in liver mitochondria. Basal respiratory rate of the mitochondrial FADH₂ 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 FADH₂ 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 H₂O₂ and reducing total ROS.

Curcumin Attenuates Cr(VI)‐Induced Ascites and Changes in the Activity of Aconitase and F1F0 ATPase and the ATP Content in Rat Liver Mitochondria

“…Mitochondrial respiratory chain complexes are main sites of ROS production and also sensitive to its action [38]. In particular, Cr(VI) decreased the activities of complexes I, II, and III and F 1 F 0 ATPase, thus leading to ROS accumulation in human and rat hepatic mitochondria [39,40]. Our results showed that K 2 Cr 2 O 7 exposure diminished the activity of complexes II and F 1 F 0 ATPase without affecting complexes III and IV.…”

Mitochondrial Oxidative Stress Is the General Reason for Apoptosis Induced by Different-Valence Heavy Metals in Cells and Mitochondria

“…Mitochondrial research. Cr 2 O 7 2− induced a state 3 and 3U FCCP respiration decrease, an ROS production increase, and ∆Ψ mito decline in isolated RLM energized by CI and CII substrates [315,316]. However, state 4 respiration increased and peaked at 250 µM K 2 Cr 2 O 7 , which was followed by a sharp decrease in respiration [316].…”

“…RLM took up Cr(VI), which reduced further to Cr(V) in the matrix [317]. Glutathione eliminated these effects of Cr 2 O 7 2− [81,315]. Cr 2 O 7 2− induced the state 3 inhibition and ∆Ψ mito decline in mitochondria isolated from L02 hepatocytes [318].…”