Iron induces hepatocytes death via MAPK activation and mitochondria-dependent apoptotic pathway: Beneficial role of glycine

Abstract

In the present study we investigated the beneficial role of glycine in iron (FeSO4) induced oxidative damage in murine hepatocytes. Exposure of hepatocytes to 20 μM FeSO4 for 3 hours enhanced reactive oxygen species (ROS) generation and induced alteration in biochemical parameters related to hepatic oxidative stress. Investigating cell signalling pathway, we observed that iron (FeSO4) intoxication caused NF-κB activation as well as the phosphorylation of p38 and ERK MAPKs. Iron (FeSO4) administration also disrupted Bcl-2/Bad protein balance, reduced mitochondrial membrane potential, released cytochrome c and induced the activation of caspases and cleavage of PARP protein. Flow cytometric analysis also confirmed that iron (FeSO4) induced hepatocytes death is apoptotic in nature. Glycine (10 mM) supplementation, on the other hand, reduced all the iron (FeSO4) induced apoptotic indices. Combining, results suggest that glycine could be a beneficial agent against iron mediated toxicity in hepatocytes.