Protective effects of zinc in indomethacin-induced gastric mucosal injury: evidence for a dual mechanism involving lipid peroxidation and nitric oxide.
BACKGROUND
Indomethacin causes gastric mucosal injury, although the pathogenesis is not fully understood. Zinc, is known to have gastroprotective effects in both humans and experimental animals.


OBJECTIVE
To determine (i) the protective effects of zinc in indomethacin-induced gastric mucosal injury in rats, and (ii) whether these cytoprotective effects are mediated by changes in gastric lipid peroxidation and/or nitric oxide synthase activity.


METHODS
Gastric lesions were induced in rats by the intragastric administration of indomethacin. Morphological changes, lipid peroxidation (malondialdehyde levels) and nitric oxide synthase activity were determined in animals pre-treated with zinc sulphate and in controls.


RESULTS
Indomethacin significantly increased malondialdehyde levels and decreased NOS activity. These effects were attenuated by pre-treatment with zinc (P < 0.005 and 0.0001, respectively). The protective effects of zinc were readily abolished in animals pre-treated with N-nitro-L-arginine methyl ester (L-NAME). Morphologically, indomethacin induced large areas of mucosal ulcerations, which were completely prevented by zinc pre-treatment.


CONCLUSIONS
Zinc provides protection against indomethacin-induced gastric mucosal injury. These protective effects result from the inhibition of lipid peroxidation and the preservation of mucosal nitric oxide synthase.
Joseph
R M
RM
Departments of Medicine and Pathology, G.V. (Sonny), Montgomery VA Medical Center and the University of Mississippi School of Medicine, Jackson, MS 39216, USA.
Varela
V
V
Kanji
V K
VK
Subramony
C
C
Mihas
A A
AA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology; D007213:Indomethacin / Q000633:toxicity*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D015032:Zinc / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D015032:Zinc; D007213:Indomethacin