PROBIOTIC YEAST TREATMENT ATTENUATES IRINOTECAN INDUCED INTESTINAL MUCOSITIS IN MICE AND IN-VITRO MODEL

JUAN IGNACIO GIRARDI; MALENA MARIA FERREYRA COMPAGNUCCI; AGUSTINA JULIANA ERREA; MARTIN RUMBO

Ouro Preto

Congreso; XLVII Annual Meeting of the Brazilian Society of Immunology; 2023

Brazilian Society of Immunology

Irinotecan, a chemotherapeutic drug used in colorectal metastatic cancer therapy, often causes severe intestinal damage, leading to drug-induced mucositis. This condition can necessitate the discontinuation of chemotherapy, impacting disease progression. In this study, we aimed to evaluate the protective effects of the probiotic yeast Kluyveromyces marxianus CIDCA 8154 (Km8154) against irinotecan-induced mucositis. We also investigated the effects of heat-killed (HK) yeast administration. In-vitro: Reporter CACO-2 cells, which express the luciferase gene under the CCL20 promoter, were treated with irinotecan and supplemented them with Km8154. The inflammatory response was measured by luciferase activity and cell oxidative stress by flow cytometry with the H2-DCFDA probe. In-vivo: Irinotecan 75mg/kg was administered to BALB/c mice for 4 days to induce drug-associated mucositis. The Km8154 intervention group received daily oral administration of the yeast at a concentration of 109 UFC/ml until the endpoint. After 7 days, mice were euthanized, and intestinal samples were obtained. Clinical, histopathological, and biochemical parameters were evaluated. Our in-vitro studies demonstrated that irinotecan treatment activated the reporter Caco-2 cells, but co-treatment with Km8154 reduced luciferase production significantly (p