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Abstract

Background: Irinotecan hydrochloride (CPT-11), a topoisomerase I inhibitor highly effective for various cancers, has its dosage limited by diffuse mucosal damage with increased prostaglandin (PG) E₂. However, an analysis of intestinal phospholipid fatty acid composition after CPT-11 treatment has not been reported. This study aimed to evaluate intestinal phospholipid fatty acid composition in relation to intestinal mucosal integrity and plasma and mucosal PGE₂ levels after CPT-11 treatment. The effect of dietary vegetable oil supplementation, perilla oil vs corn oil, was also evaluated. Methods: Intestinal phospholipid fatty acid composition, PGE₂ level, mucosal diamine oxidase (DAO) activity, diarrhea, and blood tests were evaluated in rats injected with CPT-11 under a conventional diet. The same parameters were compared among 3 different dietary vegetable oil supplementations: perilla oil, corn oil, and a 1:3, respectively, mixture with a semisynthetic diet during 14 days. Results: CPT-11 treatment caused severe diarrhea, and intestinal mucosal fatty acid composition changed with increased PGE₂ level and decreased DAO activity. Decreases in eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA/arachidonic acid (AA) ratio in colonic mucosa were observed. Perilla oil increasedω -3 polyunsaturated fatty acids, α-linolenic acid, EPA, and EPA/AA ratio and decreased plasma PGE₂. But the amounts used were not enough to attenuate intestinal damage from CPT-11 treatment. Conclusions: CPT-11 induced changes of intestinal mucosal fatty acid composition with increased PGE₂ level and decreased intestinal integrity; perilla oil shows the possibility of being able to attenuate those changes.

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Phospholipid Fatty Acid Composition and Diamine Oxidase Activity of Intestinal Mucosa From Rats Treated With Irinotecan Hydrochloride (CPT-11) under Vegetable Oil–Enriched Diets: Comparison Between Perilla Oil and Corn Oil

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