Mucosal and hepatic metabolism during the spontaneous disappearance of salicylate-induced gastric erosions.
Salicylate-induced gastric erosions have been shown to disappear despite continuing salicylic acid administration in the rat. On the other hand, numerous drugs are able to change the capacity of the gastric mucosa to conjugate xenobiotics, which gives reason to follow gastric resistance to salicylic acid and to correlate it with changes in mucosal rate of drug biotransformation reactions. Gastric and duodenal UDP glucuronyltransferase activity decreased markedly within 12 hours after a single dose of salicylic acid. when continuing salicylic acid administration, macroscopic gastric lesions disappeared within 3 days and mucosal UDP glucuronyltransferase activity increased above control level. In 2 weeks the activity returned to control level. In spite of the fact that salicylates markedly inhibited gastroduodenal glucuronidation in vitro, there was no substrate effect of salicylic acid present at the time rats were killed. Duodenal 3,4-benzpyrene hydroxylase activity was not affected by salicylic acid administration. The gastric activity of benzpyrene hydroxylase in controls and in rats treated with salicylic acid was below the sensitivity of the method. Hepatic detoxification capacity was quite stable. A slight depression of 3,4-benzpyrene hydroxylase activity did, however, take place within 2 weeks. Gastric and duodenal protein contents decreased after a single salicylic acid administration, but returned to control level in 5 days in the duodenum, and in 2 weeks in the stomach, when the administration was prolonged. The results suggest that mucosal detoxification capacity may have a role in the pathogenesis of drug-induced gastric erosions. Gastric mucosa adapts to repeated salicylic acid administration, having reduced susceptibility to drug-induced erosions.
D000818:Animals; D001711:Biotransformation; D004386:Duodenum / Q000187:drug effects / Q000201:enzymology; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D006471:Gastrointestinal Hemorrhage / Q000139:chemically induced; D014453:Glucuronosyltransferase / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D051381:Rats; D012459:Salicylates; D012980:Sodium Salicylate / Q000494:pharmacology; D013272:Stomach Diseases / Q000139:chemically induced / Q000378:metabolism*
D011506:Proteins; D012459:Salicylates; D006899:Mixed Function Oxygenases; D014453:Glucuronosyltransferase; D012980:Sodium Salicylate