Mechanism of intragastric amoxicillin protection against 96% ethanol damage in rat stomach.
The purpose of this study was to investigate the role played by endogenous prostaglandins, sulfhydryls, gastric motility, fluid volume, and mucus volume retained in the gastric lumen in the protection offered by intragastric amoxicillin against ethanol-induced gastric lesions. It has been demonstrated that intragastric administration of amoxicillin (Amx) dose-dependently protected the rat gastric mucosa from 96% ethanol-induced lesions. The inhibition of the lesions was 28, 41.4, 84.7 and 90% at doses of 50, 100, 200 and 400 mg/kg, respectively. The gastroprotective effect of Amx was significantly reversed by pretreatment with both indomethacin (5 mg/kg, subcutaneously), a cyclooxygenase inhibitors, and iodoacetamide (100 mg/kgm subcutaneously), a sulfhydryl blocker. Gastric motility was measured by a balloon method. There was not any significant differences between Amx (50-400 mg/kg)-induced and spontaneous motility with regard to both amplitudes and frequently of gastric contraction. One milliliter of 96% ethanol produced hemorrhagic bandlike lesions in the corpus mucosa with the occurrence of a complete inhibition of the amplitude and frequency of gastric contraction. This inhibition of gastric motility caused by ethanol was not modified by pretreatment of Amx (400 mg/kg) alone, indomethacin plus Amx or iodoacetamide plus Amx. In addition, there was a significant increase in the mucus volume retained in the gastric lumen for Amx (200 and 400 mg/kg) at 30 min after its administration. We conclude that the intragastric Amx prospective effect against 96% eathanol-induced mucosal lesions may be mediated by endogenous prostaglandins, sulfhydryl compounds of the gastric mucosa, an increase in mucus volume retained in the gastric lumen at the time when ethanol is administered, and is not associated with the gastric motor activity.
Department of Surgical Pathology II, Faculty of Medical Sciences, National University of Rosario, Argentina.
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Gutierrez-Cabano
D000658:Amoxicillin / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D004347:Drug Interactions; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D005769:Gastrointestinal Motility / Q000187:drug effects; D007213:Indomethacin / Q000494:pharmacology; D007460:Iodoacetamide / Q000494:pharmacology; D008297:Male; D010406:Penicillins / Q000494:pharmacology*; D011453:Prostaglandins / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D017208:Rats, Wistar
D010406:Penicillins; D011453:Prostaglandins; D000431:Ethanol; D000658:Amoxicillin; D007213:Indomethacin; D007460:Iodoacetamide