Role Of Rirr Mediated By Mptp In Iron Overload Resulted In Hepatic Damage

Objective:To investigate the role of mPTP in the burst of ROS and futher clarify the mechanism of the ROS indued by iron overload resulting in hepatic damage.Methods: In this study sixty male Kunming mice, initially weighting 14.7±0.7 g were used. Mice were randomly divided into three groups. Control group, iron–over load group, CsA group. During the course of the experiment, mice were fasted overnight. They were anesthetized with ethyl ether, and blood was collected by cardiac puncture. The liver was quickly excised, weighed and divided for analysis as described below: serum iron and liver iron and Serum AST and ALT were detected . Apoptosis was detected by TUNEL. The measurement of Mitochondrial swelling, change of mitochondrial membrane potential and ROS generation. The activity of SOD, MDA, GSH-Px and CAT in cells was measured using their special kit.Results: Iron overload can result in significant increases in liver-to-body weight ratio, serum levels of ALT and AST, mitochondrial swelling, loss of mitochondrial membrane potential(Δψ), ROS production, oxidative stress and hepatocyte apoptosis. While supplementation with cyclosporin A (CsA), a specific inhibitor of the mPTP, the above indicators were alleviated.Conclusion: These data provided support that a phenomenon termed RIRR may be involved in the burst of ROS in the liver and greatly contributed to the hepatic damage initiated by iron overload .