| Tryptamine-gallic acid hybrid prevents non-steroidal anti-inflammatory drug-induced gastropathy: Correction of mitochondrial dysfunction and inhibition of apoptosis in gastric mucosal cells. | |
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MedLine Citation:
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PMID: 22157011 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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We have investigated the gastroprotective effect of SEGA (3a), a newly synthesized tryptamine-gallic acid hybrid molecule against non-steroidal anti-inflammatory drug (NSAID)-induced gastropathy with mechanistic details. SEGA (3a) prevents indomethacin (NSAID)-induced mitochondrial oxidative stress (MOS) and dysfunctions in gastric mucosal cells, which play a pathogenic role in inducing gastropathy. SEGA (3a) offers this mitoprotective effect by scavenging of mitochondrial superoxide anion and intra-mitochondrial free iron released as a result of MOS. SEGA (3a), in vivo blocks indomethacin-mediated MOS as evident from the inhibition of indomethacin-induced mitochondrial protein carbonyl formation, lipid peroxidation and thiol depletion. SEGA (3a) corrects indomethacin-mediated mitochondrial dysfunction in vivo by restoring defective electron transport chain function, collapse of transmembrane potential and loss of dehydrogenase activity. SEGA (3a) not only corrects mitochondrial dysfunction but also inhbits the activation of mitochondrial pathway of apoptosis by indomethacin. SEGA (3a) inhibits indomethacin-induced down regulation of Bcl-2 and up-regulation of Bax genes in gastric mucosa. SEGA (3a) also inhbits indometacin-induced activation of caspase-9 and caspase-3 in gastric mucosa. Besides gastroprotective effect against NSAID, SEGA (3a) also expedites the healing of already damaged gastric mucosa. Radio labelled [99mTc labeled SEGA (3a)] tracer studies confirm that SEGA (3a) enters into mitochondria of gastric mucosal cell in vivo and it is quite stable in serum. Thus, SEGA (3a)bears an immense potential to be a novel gastroprotective agent against NSAID-induced gastropathy. |
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Authors:
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Chinmay Pal; Samik Bindu; Sumanta Dey; Athar Alam; Manish Goyal; Mohd Shameel Iqbal; Souvik Sarkar; Rahul Kumar; Kamal Krishna Halder; Mita Chatterjee Debnath; Susanta Adhikari; Uday Bandyopadhyay |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-12-7 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: - ISSN: 1083-351X ISO Abbreviation: - Publication Date: 2011 Dec |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Indian Institute of Chemical Biology, India; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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