Probiotic Yeast Treatment Attenuates Irinotecan Induced Intestinal Mucositis in Mice and In Vitro Models

GIRARDI JI; FERREYRA CMM; ERREA A; RUMBO M

Congreso; Reunión Anual de Sociedades de Biociencias: SAIC, SAI&FAIC y SAFIS; 2023

Irinotecan is a chemotherapeutic drug commonly used in colorectalmetastatic cancer therapy. It can generate intestinal cytotoxic damage, triggering a drug induced mucositis. Given its severity, it canforce the interruption of the chemotherapeutic scheme with consequent impact on disease progression. For that, we aimed to evaluatean intervention using the probiotic yeast Kluyveromyces marxianusCIDCA 8154 (Km8154), whose anti-inflammatory and anti-oxidativecapabilities and protective properties in intestinal colitis models havepreviously been reported. In-vitro: reporter CACO-2 cell line with luciferase gene under CCL20 promoter were treated with Irinotecanand supplemented with Km8154. After incubation, cells luciferaseactivity was measured to assess inflammatory response. In addition,cell oxidative stress was measured using H2-DCFDA probe by flowcytometry. In-vivo: Irinotecan 75mg/kg was administered to BALB/c mice to induce the drug associated mucositis and the Km8154intervention group had the yeast administered daily by gavage at109UFC/ml until endpoint. Seven days after the first irinotecan dose,mice were killed, and intestinal samples were obtained. Clinical, histopathological and biochemical parameters were evaluated.In-vitro studies have shown that irinotecan treatment induce activation of the reporter Caco-2 cells and Km8154 co-treatment isable to reduce the production of luciferase in irinotecan treatedcells (p=0.0018). Furthermore, irinotecan induced oxidative stressin Caco-2 cell line that is attenuated by Km8154 co-treatment(p=0.0255). In-vivo studies have shown that yeast treatment improved histopathological and diarrheal scores of mice treated withirinotecan while protecting against intestinal damage measured witha villus/crypt ratio (p=0.0006) and intestinal length shortening (p=0.0049). The probiotic yeast Km8154 is able to confer protectionagainst intestinal mucositis induced by irinotecan treatment both invitro and in vivo models.