Avaliação do efeito anti-inflamatório e antioxidante do extrato hidroalcoólico do cogumelo Agaricus blazei Murrill, dos seus polissacarídeos e da água ozonizada na mucosite intestinal induzida por 5-fluorouracil

Abstract

Mucositis is an inflammation of the mucous membrane of the gastrointestinal tract that can run from the mouth to the anus. It is a recurrent adverse effect in cancer patients, its first symptoms may appear in the second week of treatment with 5-fluorouracil (5-FU). Agaricus blazei Murrill belongs to the Fungi kingdom, its basidiocarp has macronutrients and micronutrients in its composition, it is used for the preparation of extracts and isolation of polysaccharides. This study investigated the role of the hydroalcoholic extract of the mushroom Agaricus blazei Murrill (HEAb), its polysaccharides (PAbM), ozonated water (AO) in modulating the anti-inflammatory and antioxidative response of mucositis induced by 5-FU. Mice weighing between 25-30 g, males, received a single dose of 5-FU, intraperitoneally (450 mg/kg), on the first day of the experiment. Gavage administration (0.1 mL/10 g) of HEAb (25 mg/kg), PAbM (50 mg/kg), AO (60 mcg/mL) and HEAb + AO began on the first day of treatment, 1 hour before the administration of 5-FU and for another 2 days, and was euthanized on the fourth day. After euthanasia, samples from the three intestinal segments (duodenum, jejunum, and ileum) were removed, sectioned, weighed, and frozen at -80 ºC for analysis of myeloperoxidase (MPO), malondialdehyde (MDA), reduced glutathione (GSH), interleukin 10 (IL-10), and interleukin – 1 beta (IL-1β). 5-FU was able to induce significant inflammation in the intestinal segments compared to the control group, according to histology and microscopic scores for inflammation. Pre-treatment with HEAb, PAbM and AO + HEAb reduced (p<0.05) intestinal lesions, decreased hemorrhage, edema, loss of cell architecture and inflammatory cell infiltrate caused by 5-FU. There was also a reduction (p<0.05) in MPO and MDA levels and a recovery (p<0.05) in GSH and IL-10 levels, especially in the groups treated with PAbM, HEAb and HEAb + AO, the latter with more significant results, suggesting that the combined action with AO enhances the anti-inflammatory and antioxidant efficacy of A. blazei Murrill. Interventions based on the combination of natural compounds with antioxidant and immunomodulatory action, such as Agaricus blazei Murrill and redox regulating agents, such as ozonated water, present promising alternatives.