Inhibitory effect of fluvastatin on ileal ulcer formation in rats induced by nonsteroidal antiinflammatory drug.
OBJECTIVE
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause gastrointestinal damage as one of their side effects in humans and experimental animals. Lipid peroxidation plays an important role in NSAID-induced ulceration. The aim of this study was to investigate the inhibitory effect of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors on the ulceration in small intestines of rats.


METHODS
The effects of three HMG-CoA reductase inhibitors, fluvastatin, pravastatin and atorvastatin on ileal ulcer formation in 5-bromo-2-(4-fluorophenyl)-3-(4- methylsulfonylphenyl) thiophene (BFMeT)-treated rats were examined. Antioxidative activity of the inhibitors was measured by a redox-linked colorimetric method.


RESULTS
Fluvastatin, which was reported to have antioxidative activity, repressed the ileal ulcer formation in rats treated with BFMeT an NSAIDs. However, the other HMG-CoA reductase inhibitors (pravastatin and atorvastatin) did not repress the ileal ulcer formation. Among these HMG-CoA reductase inhibitors, fluvastatin showed a significantly stronger reducing power than the others (pravastatin, atorvastatin).


CONCLUSIONS
Fluvastatin having the antioxidaitive activity suppresses ulcer formation in rats induced by NSAIDs.
Hagiwara
Mari
M
Department of Molecular Bacteriology, Graduate School of Medicine, The University of Tokushima, Tokushima 770-8503, Japan.
Kataoka
Keiko
K
Arimochi
Hideki
H
Kuwahara
Tomomi
T
Nakayama
Haruyuki
H
Ohnishi
Yoshinari
Y
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants / Q000494:pharmacology; D000069059:Atorvastatin; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology*; D000077340:Fluvastatin; D006538:Heptanoic Acids / Q000494:pharmacology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007077:Ileal Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007082:Ileum / Q000473:pathology; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D017035:Pravastatin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014456:Ulcer / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000975:Antioxidants; D005229:Fatty Acids, Monounsaturated; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; D011758:Pyrroles; D000077340:Fluvastatin; D000069059:Atorvastatin; D017035:Pravastatin
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