Novel Role of Famotidine in Downregulation of Matrix Metalloproteinase-9 during Protection of Ethanol-induced Acute Gastric Ulcer
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Novel Role of Famotidine in Downregulation of Matrix Metalloproteinase-9 during Protection of Ethanol-induced Acute Gastric Ulcer
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| Creator |
Singh, Laishram Pradeepkumar
Kundu, Parag Ganguly, Krishnendu Mishra, Amartya Swarnakar, Snehasikta |
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| Subject |
Drug Development/Diagnostics & Biotechnology
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| Description |
Gastric ulcer is a multifaceted process including acid secretion, reactive oxygen species generation, prostaglandin inhibition, and extracellular
matrix (ECM) degradation. Matrix metalloproteinases (MMPs) have the ability to cleave and remodel the ECM. We investigated the activity and
expression of MMP-9 and -2 in ethanol-induced acute gastric ulceration in rats. We found that severity of gastric ulcer was strongly correlated with
increasing doses of ethanol and increased secretion of proMMP-9. ProMMP-9 was upregulated ∼25-fold at maximum ulcer index. Increased
secretion of proMMP-9 was associated with increased expression of tumor necrosis factor-α and interleukin-6. We examined the effect of H2-
receptor antagonists and antioxidants on proMMP-9 secretion and synthesis during prevention of ethanol-induced gastric ulcer. Our data reveal that
famotidine dose dependently blocked increased secretion and synthesis of proMMP-9 during gastroprotection and arrested infiltration of
inflammatory cells as well as oxidative stress in rat gastric tissues. Similar to H2-receptor antagonists, N-acetylcysteine and dimethyl sulfoxide,
well-known antioxidants, inhibited proMMP-9 upregulation to the control level. In conclusion, ethanol-induced gastric ulceration is associated with
increased expression of proMMP-9 that can be attenuated by H2-receptor antagonists and antioxidants. These findings furnish a novel MMP-9-
mediated pathway and its inhibition via proinflammatory cytokines by famotidine in ethanol-induced gastric ulceration.
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| Date |
2007
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/1135/1/FREE_RADICAL_BIOLOGY_AND_MEDICINE__43_(2)_289%2D299_;2007[64].pdf
Singh, Laishram Pradeepkumar and Kundu, Parag and Ganguly, Krishnendu and Mishra, Amartya and Swarnakar, Snehasikta (2007) Novel Role of Famotidine in Downregulation of Matrix Metalloproteinase-9 during Protection of Ethanol-induced Acute Gastric Ulcer. Free Radical Biology & Medicine, 43 (2). pp. 289-299. |
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| Relation |
http://dx.doi.org/10.1016/j.freeradbiomed.2007.04.027
http://www.eprints.iicb.res.in/1135/ |
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