Ação da n-acetilcisteína em modelos murinos de colite ulcerativa moderada e grave induzidas por sulfato de sódio dextrana

Abstract

Ulcerative Colitis is an inflammatory bowel disease characterized by chronic inflammation of the mucosa of colon, with relapsing character and etiology not yet determined. Continuous inflammation and oxidative stress on the intestinal epithelium are involved in the breakdown of the epithelial barrier and increased intestinal permeability, facilitating the entry of luminal antigens that may diffuse through the bloodstream and cause inflammation in distant organs, thus characterizing extraintestinal manifestations. Antioxidant and anti-inflammatory alternatives have been investigated, in the context of colitis, especially N-acetylcysteine (NAC), a potent reducing agent and precursor of glutathione. In this context, this work investigated the effects of oral administration of NAC on the antioxidant and inflammatory profiles of colon and kidney, in experimental models of moderate and severe ulcerative colitis, induced by sodium dextran sulfate (SDS). For this, 31 male mice were randomized into 5 groups: Control (C), Moderate Colitis (CM), Severe Colitis (CG), Moderate Colitis treated with NAC (NACM) and Severe Colitis treated with NAC (NACG). For 37 days, the animals, in the supplemented groups, received 150 mg kg d-1 of NAC in the drinking water. From 31st to 37th days, moderate and severe colitis were induced in their respective groups, by adding SDS in drinking water - 3 and 5% (w / v), respectively. Histological analysis of the colon, determination of antioxidant activity (superoxide dismutase - SOD, catalase - CAT, reduced GSH, oxidized glutathione - GSSG and their ratio - GSH / GSSG) and oxidative stress markers (hydrogen peroxide - H2O2, malondialdehyde – MDA) and inflammatory profile (myeloperoxidase - MPO, tumor necrosis factor alpha - TNF - α, interleukin 6 - IL - 6, interferon gamma - IFN - γ and interleukin 10 - IL - 10). After determination of the normality of the data, parametric or non-parametric tests were used, and significance was considered, when p <0.05. Histological analysis showed that SDS (3 and 5% w / v) induced colitis, causing destruction of the crypt architecture and administration with NAC partially restored this damage. In the colon, only moderate colitis (CM group) stimulated SOD in detriment of CAT and GSH that were reduced (this was also verified in severe colitis - CG), where NAC administration had no influence (NACM and NACG). Although H2O2 levels were not altered, oxidative damage was evidenced when NAC was offered in severe colitis (↑ MDA), which was corroborated by ↑ TNF-α, even though it was not observed at the histological level. At the renal level, SDS (3% and 5% w / v) increased the CAT requirement, being significant when administered to NAC in severe colitis (NACG). In addition, the NAC improved the endogenous antioxidant capacity (↑ GSH), significantly in the moderate colitis - NACM. However, similar to the colon, it caused oxidative damage to membranes (↑ MDA), expressive in severe colitis (NACG). In view of the divergent results in the evaluated organs (colon and kidney), the clinical application of NAC, especially in colitis, should be evaluated carefully