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Melatonin reduces indomethacin‐induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis
Author(s) -
Maity Pallab,
Bindu Samik,
Dey Sumanta,
Goyal Manish,
Alam Athar,
Pal Chinmay,
Reiter Russel,
Bandyopadhyay Uday
Publication year - 2009
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2009.00663.x
Subject(s) - melatonin , apoptosis , oxidative stress , mitochondrion , downregulation and upregulation , gastric mucosa , cytochrome c , reactive oxygen species , pharmacology , caspase 3 , biology , microbiology and biotechnology , chemistry , programmed cell death , endocrinology , biochemistry , stomach , gene
Augmentation of gastric mucosal cell apoptosis due to development of oxidative stress is one of the main pathogenic events in the development of nonsteroidal anti‐inflammatory drug (NSAID)‐induced gastropathy. Identification of a nontoxic, anti‐apoptotic molecule is warranted for therapy against NSAID‐induced gastropathy. The objective of the present study was to define the mechanism of the anti‐apoptotic effect of melatonin, a nontoxic molecule which scavenges reactive oxygen species. Using an array of experimental approaches, we have shown that melatonin prevents the development of mitochondrial oxidative stress and activation of mitochondrial pathway of apoptosis induced by indomethacin (a NSAID) in the gastric mucosa. Melatonin inhibits the important steps of indomethacin‐induced activation of mitochondrial pathway of apoptosis such as upregulation of the expression of Bax and Bak, and the downregulation of Bcl‐2 and BclxL. Melatonin also prevents indomethacin‐induced mitochondrial translocation of Bax and prevents the collapse of mitochondrial membrane potential. Moreover, melatonin reduces indomethacin‐mediated activation of caspase‐9 and caspase‐3 by blocking the release of cytochrome c and finally rescues gastric mucosal cells from indomethacin‐induced apoptosis as measured by the TUNEL assay. Histologic studies of gastric mucosa further document that melatonin almost completely protects against gastric damage induced by indomethacin. Thus, melatonin has significant anti‐apoptotic effects to protect gastric mucosa from NSAID‐induced apoptosis and gastropathy, which makes its use as potential therapy against gastric damage during NSAID treatment.