Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis

Pallab Maity, Samik Bindu, Sumanta Dey, Manish Goyal, Athar Alam, Chinmay Pal, Russel J Reiter, Uday Bandyopadhyay

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)314-323
Number of pages10
JournalJournal of Pineal Research
Volume46
Issue number3
DOIs
StatePublished - Apr 2009

Fingerprint

Melatonin
Indomethacin
Stomach
Oxidative Stress
Apoptosis
Anti-Inflammatory Agents
Gastric Mucosa
Pharmaceutical Preparations
Caspase 9
Mitochondrial Membrane Potential
In Situ Nick-End Labeling
Cytochromes c
Caspase 3
Reactive Oxygen Species
Up-Regulation
Down-Regulation
Therapeutics

Keywords

  • Apoptosis
  • Gastric damage
  • Indomethacin
  • Melatonin
  • Mitochondria

ASJC Scopus subject areas

  • Endocrinology

Cite this

Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. / Maity, Pallab; Bindu, Samik; Dey, Sumanta; Goyal, Manish; Alam, Athar; Pal, Chinmay; Reiter, Russel J; Bandyopadhyay, Uday.

In: Journal of Pineal Research, Vol. 46, No. 3, 04.2009, p. 314-323.

Research output: Contribution to journalArticle

Maity, Pallab ; Bindu, Samik ; Dey, Sumanta ; Goyal, Manish ; Alam, Athar ; Pal, Chinmay ; Reiter, Russel J ; Bandyopadhyay, Uday. / Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. In: Journal of Pineal Research. 2009 ; Vol. 46, No. 3. pp. 314-323.
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