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Matrix metalloproteinase‐9 activity and expression is reduced by melatonin during prevention of ethanol‐induced gastric ulcer in mice
Author(s) -
Swarnakar Snehasikta,
Mishra Amartya,
Ganguly Krishnendu,
Sharma Anamika Vivek
Publication year - 2007
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.2007.00443.x
Subject(s) - melatonin , matrix metalloproteinase , ethanol , medicine , endocrinology , metalloproteinase , chemistry , lipid peroxidation , extracellular matrix , pharmacology , biochemistry , enzyme
Matrix metalloproteinases (MMPs) play an important role in degradation of gastric extracellular matrix proteins. However, no reports are available on the relationship between the activity of MMPs and gastric ulceration induced by alcohol. Our objective was to investigate the effect of melatonin ( N ‐acetyl‐5‐methoxytryptamine) on the regulation of MMP‐9 and MMP‐2 activities during prevention of ethanol‐induced gastric ulcer. Biochemical and zymographic methods were used to analyze MMP‐9 and ‐2 activities in gastric tissues of Balb/c mice following induction of gastric ulcer by ethanol. Our studies reveal that melatonin arrested cell injury, protein carbonyl formation, and lipid peroxidation in mice during gastroprotection. Melatonin dose‐dependently reduced proMMP‐9 activity that was induced (∼ 25‐fold) during ethanol‐induced gastric ulceration. Severity of gastric ulcers were correlated proportionately with increased dose of ethanol and elevated activity of proMMP‐9 and ‐2. The reduced activities of MMP‐9 and ‐2 were associated with reduced expression of TNF‐ α and increased expression of tissue inhibitors of metalloproteinases (TIMP‐1 and TIMP‐2). We conclude that melatonin's ability to prevent ethanol‐induced gastric ulceration in mice is related to a reduction in proMMP‐9 activity and expression.