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

Sudip Bhattacharyya, Jyotirmoy Ghosh, Parames C Sil

Index: Free Radic. Res. 46(10) , 1296-307, (2012)

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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.