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) E(2). 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 PGE(2) 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, PGE(2) 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 PGE(2) 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 increased omega-3 polyunsaturated fatty acids, alpha-linolenic acid, EPA, and EPA/AA ratio and decreased plasma PGE(2). 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 PGE(2) level and decreased intestinal integrity; perilla oil shows the possibility of being able to attenuate those changes.