The Anthocyanidins Malvidin and Cyanidin Alleviate Irinotecan-Triggered Intestinal Mucositis by Modulating Oxidative Stress and Cytokine Release

TL;DR

The study shows that anthocyanidins malvidin and cyanidin reduce intestinal damage caused by chemotherapy by lowering oxidative stress and inflammation, but they don't fully prevent weight loss or tissue damage.

Contribution

The novel contribution is identifying distinct protective mechanisms of malvidin and cyanidin in modulating oxidative stress and cytokine responses in chemotherapy-induced mucositis.

Findings

Malvidin and cyanidin both reduced oxidative stress markers in the duodenum and colon.

Malvidin showed broader anti-inflammatory effects, reducing IL-1β and IL-17 in both intestinal segments.

Neither compound prevented weight loss or histopathological damage, suggesting additional mechanisms are needed for mucosal repair.

Abstract

Chemotherapy with irinotecan (CPT-11) induces intestinal mucositis via oxidative stress and NF-κB-driven cytokine amplification. We investigated the protective effects of the anthocyanidins cyanidin and malvidin (5 mg/kg) in a murine CPT-11 mucositis model. Both compounds increased duodenal glutathione level (GSH) and reduced lipid peroxidation (MDA), with distinct antioxidant profiles: malvidin enhanced catalase (CAT) activity, while cyanidin elevated superoxide dismutase (SOD). In the colon, cyanidin lowered MDA, whereas other oxidative and inflammatory markers remained largely unchanged. Malvidin significantly reduced IL-1β and IL-17 in both intestinal segments; cyanidin selectively decreased IL-6 in the colon, and this reduction was also observed for malvidin treatment. Gene expression analysis revealed broad transcriptional suppression in the duodenum for both compounds (Nrf2, NF-κB, TNF-α, IL-1β, IL-6, IL-17, IL-10), while colonic effects were more limited (suppression in IL-6 for both compounds). Despite these biochemical and transcriptional improvements—which were more pronounced with malvidin—neither compound prevented CPT-11-induced weight loss or colonic histopathology, indicating that redox and cytokine modulation alone are insufficient to restore mucosal integrity. Overall, malvidin demonstrated a more significant modulation in the antioxidant response in the duodenum, with anti-inflammatory activity in both segments, while cyanidin showed targeted modulation of oxidative stress. These findings position both anthocyanidins as complementary agents with distinct mechanistic profiles, warranting further investigation into dose–response, pharmacokinetics, NRF2 protein dynamics, and barrier-repair strategies. Early-phase clinical evaluation is recommended to assess their potential as adjunctive therapies for chemotherapy-induced intestinal mucositis.

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