Prophylactic Effect of Lafutidine against Adverse Reaction Induced in Rat Stomach by Repeated Administration of 5-Fluorouracil
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Accession number;04A0774348
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| Title;Prophylactic Effect of Lafutidine against Adverse Reaction Induced in Rat Stomach by Repeated Administration of 5-Fluorouracil |
| Author;
NAKAGIRI AKARI
(Kyoto Pharmaceutical Univ., JPN)
NAKASHIMA MASATO
(Kyoto Pharmaceutical Univ., JPN)
FUKUSHIMA KAZUHIRO
(Kyoto Pharmaceutical Univ., JPN)
TAKEUCHI KOJI
(Kyoto Pharmaceutical Univ., JPN)
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Journal Title;Japanese Pharmacology & Therapeutics
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Journal Code:Z0947A
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ISSN:0386-3603
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VOL.32;NO.9;PAGE.551-560(2004)
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| Figure&Table&Reference;FIG.10, REF.21 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;We examined the prophylactic effect of lafutidine, a novel antiulcer drug, on the morphological and functional derangement of rat stomach after administration of 5-fluorouracil (5-FU) with or without taurocholate Na (TC). Male SD rats were given 5-FU p.o. once daily for 5 days. After 18 hr fasting, the stomach was mounted on an ex-vivo chamber, and both transmucosal potential difference (PD) and gastric mucosal blood flow (GMBF) were simultaneously measured. In some cases, the stomach was perfused with 100 mM HCl and exposed to 20mM TC for 30min. Repeated administration of 5-FU (100mg/kg) reduced basal PD with the reduced mucosal height, and caused minimal damage in the stomach when perfused with 100mM HCl for 2 hr. 5FU treatment had no influence on the reduced PD response caused by TC, but significantly attenuated the increase in GMBF following exposure to TC, resulting a significant aggravation of gastric damage. Lafutidine (30mg/kg), given together with 5-FU for 5 days, significantly antagonized the deleterious effect of 5-FU on basal PD and partially the GMBF response to TC, and significantly prevented the aggravation by 5-FU treatment of TC-induced gastric damage. These effects of lafutidine were not mimicked by cimetidine (100mg/kg) given together with 5-FU, and disappeared in the animal with chemical ablation of capsaicin-sensitive afferent neurons. 5-FU treatment also caused a decrease in body weight, and these changes were also partially antagonized by rafutidine but not cimetidine. These results suggest that 1) 5-FU treatment caused the morphological and functional derangement of the stomach and increased the mucosal vulnerability against acid, 2) lafutidine is effective in preventing such changes caused by 5-FU and 3) this effect of lafutidine is not related with acid inhibition due to histamine H2 receptors but mediated at least partly through capsaicin-sensitive afferent neurons. (author abst.) |
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