Dietary Glucosylceramide Attenuates Irinotecan-Induced Jejunal Inflammation in Mice without Altering Apoptotic Signaling in the Jejunum.

Irinotecan (IRI) is a widely used anticancer agent; however, its clinical use is often associated with severe gastrointestinal toxicity, particularly intestinal inflammation. Rice-derived lipophilic fractions and glucosylceramide (GlcCer), a major plant sphingolipid, exert anti-inflammatory effects in the colon; however, it remains unclear whether these effects extend to the small intestine, the primary site of nutrient absorption. This study investigates the protective effects of dietary GlcCer and rice extract (RE) against IRI-induced jejunal injury in mice. Female ICR mice were fed experimental diets containing GlcCer or RE for 10 days, followed by intraperitoneal administration of IRI for 4 days. Jejunal tissues were evaluated using histopathological analysis and protein array profiling of inflammation-related cytokines and apoptosis-related proteins. IRI treatment induced marked villus atrophy and crypt hypertrophy in the jejunum, accompanied by pronounced increases in inflammation-related cytokine expression levels. Dietary GlcCer substantially attenuated these morphological and inflammatory alterations, whereas apoptosis-associated nuclear changes and cleaved caspase-3 expression were largely unaffected. Dietary RE also modulated inflammatory responses, despite containing lower amounts of GlcCer, suggesting contributions from additional lipophilic components. These findings indicate that dietary GlcCer is a key bioactive constituent that attenuates IRI-induced jejunal inflammation, while leaving jejunal cleaved caspase-3 expression and apoptosis-associated nuclear changes largely unaffected. Thus, dietary GlcCer or rice-derived lipophilic fractions represent candidate nutritional strategies to mitigate local gastrointestinal toxicity associated with IRI chemotherapy.