Effect of ulceration on rat gastric tissue polyamine contents in response to different procedures; inhibition of these effects by cimetidine.
The effects of cimetidine an H2 receptor histamine antagonist on aspirin- and cold-restraint-stress-induced gastric lesions have been studied in rats. Cimetidine had a pronounced inhibitory effect on gastric lesions induced by either oral administration of aspirin (400 mg kg-1) or by cold-restraint stress in rats. These inhibitory effects were dose-related in the aspirin treatment group being 47 and 85% (P<0.05 and P<0.001) at 37.5 and 75 mg kg-1 doses, respectively, when compared to the control. Cimetidine was found effective in cold stress but inhibition with the low dose was not significant. However, high dose (75 mg kg-1) showed a significant reduction (P<0.01) in lesion index. In another series of experiments with the same regimen, the effects of different ulcerogenic procedures on the rat gastric tissue polyamine contents (putrescine, spermine and spermidine) and monoacetyl derivatives (N1- and N8-acetylspermidine) have been investigated by using HPLC method. The procedure permits use of n-octane sulphonate as an ion pairing agent on the reversed-phase column. The treatment of rats with aspirin caused a substantial decrease in the concentration of different polyamine contents in the glandular part of stomach tissue. Pretreatment with cimetidine showed a marked protection against this decline in polyamine contents at both the doses tested (37.5 mg kg-1 and 75 mg kg-1) and increased the contents of spermidine and spermine above the control values. In the other part, cold-restraint stress also declined the polyamine contents. Low dose of cimetidine was found ineffective in this model. However, a high dose of cimetidine caused a significant rise in the levels of spermidine and spermine (P<0.001 and P<0.01, respectively) above the control levels. These findings suggest that cimetidine, besides being a H2-receptor antagonist, prevents ulcer formation due to its growth promotional properties, possibly through an increase in tissue polyamine contents that offer a defense barrier against the oxygen-derived free radicals involved in the etiology of ulceration. It is also suggested that the rise in polyamine contents of gastric tissue is a crucial event in cytoprotection against destructive stimuli.
Al-shabanah
O A
OA
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia.
Raza
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M
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002927:Cimetidine / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D011073:Polyamines / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013270:Stomach / Q000187:drug effects*; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000897:Anti-Ulcer Agents; D011073:Polyamines; D002927:Cimetidine; D001241:Aspirin