Dietary Glucosylceramide Attenuates Irinotecan-Induced Jejunal Inflammation in Mice without Altering Apoptotic Signaling in the Jejunum
Abstract
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.
Related
- Cycloastragenol Attenuates Cisplatin-Induced Ovarian Toxicity in Rats: Associations With TERT Expression, Apoptotic Balance, and FOXO3a-mTOR-Related Signaling.
- Pimpinella brachycarpa extract attenuates periodontal inflammation by modulating the PI3K/Akt–NF-κB signaling pathway
- Glycyrrhizic acid attenuates corneal inflammation and pathological angiogenesis through FAK/PI3K/AKT signaling
- Prohibitive Effects of ω-3 on Pancreatic Damage in an Experimental Diabetes Model: Blood Glucose, Insulin, Lipid Profiles, Oxidative Stress, Inflammation, Pancreatic Tissue Morphology, and Apoptotic Pathways.
- CXCR5 regulates CD8+/GZMB+ T cell infiltration and apoptotic signaling in breast cancer
BibTeX
@article{ota2026dietary,
title = {{Dietary Glucosylceramide Attenuates Irinotecan-Induced Jejunal Inflammation in Mice without Altering Apoptotic Signaling in the Jejunum}},
author = {Momoka Ota and Shinji Yamashita and Yuki Yokota and Kazuhiko Aida and Mikio Kinoshita},
journal = {Journal of Oleo Science},
year = {2026},
month = aug,
doi = {10.5650/jos.ess26017},
url = {https://www.jstage.jst.go.jp/article/jos/75/8/75_jos.ess26017/_article},
note = {CC BY},
}
RIS
TY - JOUR
TI - Dietary Glucosylceramide Attenuates Irinotecan-Induced Jejunal Inflammation in Mice without Altering Apoptotic Signaling in the Jejunum
AU - Momoka Ota
AU - Shinji Yamashita
AU - Yuki Yokota
AU - Kazuhiko Aida
AU - Mikio Kinoshita
PY - 2026
DA - 2026/08/01
JO - Journal of Oleo Science
DO - 10.5650/jos.ess26017
UR - https://www.jstage.jst.go.jp/article/jos/75/8/75_jos.ess26017/_article
AB - 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.
SN - 1347-3352
SN - 1345-8957
ER -