Bacillus clausii Attenuates 5-Fluorouracil-Induced Intestinal Mucositis in Mice

克劳氏芽孢杆菌减轻小鼠 5-氟尿嘧啶诱发的肠粘膜炎

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作者:Francisco Ronaldo Farias Lima, Carlos Eduardo da Silva Monteiro, Samara Rodrigues Bonfim Damasceno, Patricia da Silva Pantoja, Álvaro Xavier Franco, Renan Oliveira Silva, Johnatan Alisson Oliveira Sousa, Tiago Santos Mendes, Marcos Aurélio Lima, Priscilla Fernanda Campos Justino, Marcellus Henrique

Abstract

5-Fluorouracil (5-FU) is an antimetabolite widely prescribed in cancer treatments, but its use in highly proliferative tissues can cause significant problems such as mucositis. Bacillus clausii is a probiotic commonly used for protection against acute diarrhea, gastrointestinal dysbiosis and inflammatory bowel diseases. We investigated the effect of B. clausii on 5-FU intestinal mucositis in mice. B. clausii was administered concomitantly with 5-FU on the first day and alone for the other two days. After the third day of 5-FU (450 mg/kg, ip), the animals were euthanized. Ileum samples were removed for evaluation for histopathological and biochemical analyses (myeloperoxidase (MPO), glutathione (GSH), malondialdehyde (MDA), catalase (CAT), interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α). In addition, we investigated gastric emptying and intestinal transit, intestinal permeability, intestinal smooth muscle contractility, transepithelial electrical resistance and intestinal transport of water and electrolytes. B. clausii reduced histopathological scores and increased the villus/crypt ratio in all intestinal segments after mucositis. B. clausii attenuated 5-FU-induced weight loss. The probiotic treatment increased GSH levels, reduced MPO and CAT activity, and also reduced MDA, IL-1β and TNF-α levels. B. clausii attenuated the delay in gastric emptying, water and electrolyte secretion and intestinal hypercontractility, and increased 5-FU-induced intestinal permeability. Thus, our data suggest that B. clausii may be a potential candidate for the treatment of chemotherapy-induced intestinal mucositis.

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