Efeito da suplementação de ácido lipoico e/ou N-Acetilcisteína sobre biomarcadores de estresse oxidativo e de inflamação em ratos com colite ulcerativa leve induzida por sulfato de sódio dextrana

Abstract

Lipoic Acid (LA) and N-acetylcysteine (NAC) are two powerful antioxidant and anti-inflammatory agents, used in various clinical and pathological conditions, among them, ulcerative colitis, UC, an inflammatory bowel disease, which has, as possible etiologic agents, oxidative stress and alteration in the immune response. In this context, this study aims to evaluate the antioxidant and anti-inflammatory effects of LA supplementation and/or N-acetylcysteine in the colon and liver of rats with mild UC induced by dextran sodium sulphate (DSS). The trial was divided into pre-treatment (7 days) and treatment (5 days). In these phases, the animals of LA groups, NAC and LA + NAC received supplements (100 mg.kg.d-1) (alone or combined) as a single daily dose, with commercial feed. In the treatment phase, except the control group, all animals received DSS 2% (p/v), administered in drinking water. Beyond general data (weight gain, food intake and organ weight), serological and hematological markers were evaluated, in addition to histological, oxidative and inflammatory ones, in colon and liver samples of these animals. Statistical analysis was performed, using parametric and nonparametric equivalents for comparison between two or multiple groups. The significance was set at p<0.05. There were no significant differences in intake and absolute and relative weights of the liver and colon. However, food intake for all groups was significantly reduced in the treatment phase when compared to pre-treatment phase. Among the several evaluated serologic markers (glucose and lipid profile, injury and liver function markers), there was an increase in levels of liver transaminases (alanine aminotransferase - ALT and aspartate aminotransferase - AST) in LA + NAC group. Hematological analysis identified reduction in levels (p <0.05) of hemoglobin and red blood cells in Mild Colitis group, and leukocytosis (p <0.05) in Mild Colitis and LA + NAC groups (both vs control group). Colonic oxidative stress (increased hydrogen peroxide - H2O2, nitrite and malondialdehyde - MDA) occurred before the changes in pro-inflammatory cytokines (tumor necrosis factor alpha - TNF- - and Interferon gamma - INF). Even in the colon, NAC could completely restore the levels of H2O2 and MDA and reduce the activity of myeloperoxidase. Moreover, the combination of LA + NAC significantly increased TNF- and IL-10 in this tissue. A hepatotoxic action in liver tissue of mild colitis group was evidenced. It was not observed hepatic injury in Mild Coliltis group. However, the combination LA + NAC caused liver damage observed by increase in ALT and AST, H2O2 and in TNF- and INF cytokines. Thus, the light-induced colitis model SSD oxidative stress prior to the elevation of TNF- and INF and there was no liver injury at the initial stage of the disease. In addition, NAC showed better antioxidant activity when compared to the combination of ALA and ALA + NAC showed proinflammatory action in the liver and colon, and liver prooxidant