| Texto completo | |
| Autor(es): Mostrar menos - |
Machado, Giovana Filocomo
;
Pereira, Quelita Cristina
;
Fagundes, Felipe Leonardo
;
Emilio-Silva, Maycon Tavares
;
Rodrigues, Vinicius Peixoto
;
Patino, Mariana De Almeida
;
Jorge, Giulia Izzo
;
Pereira, Jose Aires
;
Martinez, Carlos Augusto Real
;
Hiruma-Lima, Clelia Akiko
;
Dos Santos, Raquel De Cassia
Número total de Autores: 11
|
| Tipo de documento: | Artigo Científico |
| Fonte: | INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES; v. 26, n. 21, p. 18-pg., 2025-11-05. |
| Resumo | |
Chemotherapy with irinotecan (CPT-11) induces intestinal mucositis via oxidative stress and NF-kappa B-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-1 beta 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-kappa B, TNF-alpha, IL-1 beta, 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. (AU) | |
| Processo FAPESP: | 16/20600-0 - Investigação da atividade farmacológica de antocianinas em modelos experimentais de distúrbios gastrintestinais: úlcera péptica e mucosite intestinal |
| Beneficiário: | Raquel de Cássia dos Santos |
| Modalidade de apoio: | Auxílio à Pesquisa - Regular |