Induction of matrix metalloproteinase-9 and -3 in nonsteroidal anti-inflammatory drug-induced acute gastric ulcers in mice: regulation by melatonin
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Induction of matrix metalloproteinase-9 and -3 in nonsteroidal
anti-inflammatory drug-induced acute gastric ulcers in mice:
regulation by melatonin
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| Creator |
Ganguly, Krishnendu
Swarnakar, Snehasikta |
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| Subject |
Drug Development/Diagnostics & Biotechnology
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| Description |
The pathogenesis of gastric ulcer is associated with remodeling of
extracellular matrix (ECM) by various matrix metalloproteinases (MMPs).
However, how MMPs are regulated during nonsteroidal anti-inflammatory
drug (NSAID)-induced acute gastric ulceration is not well studied. In this
study, different NSAIDs (80 mg/kg b.w.) were applied to generate acute
gastric ulcer in the BALB/c mouse and the regulation of MMPs were
investigated. NSAIDs caused dose-dependent induction in MMP-9 and -3
activities and expressions in ulcerated gastric tissues along with significant
infiltration of inflammatory cells and disruption of gastric mucosal layer. In
addition, an increase in tumor necrosis factor (TNF)-a, interleukin (IL)-1b
and IL-8 expression, excessive generation of hydroxyl radical (•OH), and
protein oxidation and lipid peroxidation were observed in acute ulcerated
gastric tissues. In this study, the efficacy of melatonin on activities of MMP-9
and -3 during prevention of gastric ulcers was tested. Melatonin at a dose
of 60 mg/kg b.w. downregulated MMP-9 and -3 both at the enzyme and
protein levels in mouse gastric tissues during prevention as well as healing of
acute gastric ulcers. It also blocked oxidative stress via inhibition of protein
oxidation, lipid peroxidation, •OH generation and SOD-2 expression.
Moreover, it suppressed myeloperoxidase activity and expressions of TNF-a,
IL-1b and IL-8. This study documents for the first time that induction of
MMP-9 and -3 activities accompany NSAID-induced inflammation and
oxidative stress in gastric tissues and indicates that, melatonin may be a
preventive or therapeutic remedy for gastric ulcers.
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| Publisher |
Blackwell Publishing
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| Date |
2009
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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/227/1/JOURNAL_OF_PINEAL_RESEARCH%2C47(1)%2C43%2D55%2C2009[38].pdf
Ganguly, Krishnendu and Swarnakar, Snehasikta (2009) Induction of matrix metalloproteinase-9 and -3 in nonsteroidal anti-inflammatory drug-induced acute gastric ulcers in mice: regulation by melatonin. Journal Of Pineal Research, 47 (1). pp. 43-55. |
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| Relation |
http://dx.doi.org/10.1111/j.1600-079X.2009.00687.x
http://www.eprints.iicb.res.in/227/ |
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