Efeito de Lactobacillus delbrueckii CIDCA 133 e seus produtos secretados na mucosite intestinal induzida por 5-fluorouracil

Abstract

The 5 fluourouracil (5FU) is a chemotherapeutic agent used for the treatment of several types of cancer, the nonspecific mechanism of action of the drug leads to the development of side 5 effects, with intestinal mucositis being the most prevalent. Modulation of the microbiota may contribute to the protection of the epithelial barrier and intestinal homeostasis, and the use of probiotics has been studied due to its therapeutic potential in mucositis. Lactobacillus delbrueckii subsp. lactis CIDCA 133 has demonstrated probiotic potential both in vivo and in vitro. The present study evaluated the probiotic potential of the L. delbrueckii CIDCA 133 strain, 10 in its viable form, inactivated by heat (paraprobiotic) and its secreted products (postbiotics) in an experimental model of 5-FU-induced intestinal mucositis. For this, BALB/c mice (n=6/group) were divided, as follows: I-CTL (negative control), II-MUC (positive control), III MUC+MRS (culture medium control), IV-MUC+CIDCA 133 viable (probiotics), V- MUC+CIDCA 133 heat-inactivated (paraprobiotics), and VI- MUC+ SN CIDCA 133 viable (postbiotics). The 15 animals were treated by gavage with saline solution (group I and II), MRS (group III), CIDCA 133 viable 109 UFC/mL (group IV), CIDCA 133 heat-inactivated 109 CFU/mL (group V), and SN of CIDCA 133 viable (group VI) for 13 days. Intestinal mucositis was induced in groups II to VI with a single intraperitoneal injection of 5-FU (300 mg/kg) at 10° day of experimentation and was euthanized 72 hours later. The results demonstrate that probiotic, paraprobotic and 20 posbiotic were able to decrease the neutrophil inflammatory infiltrate and gene expression of the pro-inflammatory cytokine Il12p40, in addition to increasing the relative gene expression of Claudine (Cldn2). Supplementation with probiotics and paraprobotics were also able to negatively regulate the relative gene expression of Tnf and positively that of ll10. However, only the administration of probiotics was able to decrease the recruitment of eosinophils. 25 Similarly, only administration of probiotics was able to prevent increased inflammatory infiltrate of eosinophils, and only paraprobiotics prevents the increase of Il1b and the shortening of villus. Based on these results, the present study demonstrated that CIDCA 133 probiotic, paraprobiotic and postbiotic were able to partially attenuate the inflammatory and histopathological parameters of the intestinal mucositis induces by antineoplastic 5-FU, 30 however, new studies should be conducted to elucidate the mechanisms related to the beneficial effects found in the present study.