Atividade antioxidante e anti-inflamatória mediada pelo composto lassbio-294 no modelo experimental de colite ulcerativa induzida por ácido acético

Abstract

Inflammatory bowel diseases (IBD) refers to a chronic gastrointestinal inflammatory condition that affects in the gastrointestinal tract, being divided into ulcerative colitis and Crohn's disease, which are chronic diseases with no determined etiology and currently do not have an effective treatment. Since the LASSbio-294 compound has shown anti-inflammatory effects, generating vasodilatation, analgesia and pain inhibition, this work had the aim to study the effects of this compound in an experimental model of ulcerative colitis induced by acetic acid in swiss mice. In this work, 49 male swiss mice (25-30g) were used, divided into 7 groups of 7 animals. Initially, colitis was induced by 6% acetic acid and the mice were treated intraperitoneally using LASSBio-294 (0.2; 0.5; 1 mg / kg, i.p); or dexamethasone (2 mg / kg, i.p.), 17:30 hour after colitis induction. After 18 hour of colitis induction, the animals were euthanized and had a 5 cm colon sample taken for evaluation of macroscopic scores, wet weight, myeloperoxidase activity, colonic levels of malondialdehyde, glutathione, proinflammatory cytokines and dosage of iNOS expression. From the results, it was observed that with LASSBio-294 treatments there was a reduction of macroscopic scores and decreasing of the wet weight, and that the 1 mg/kg LASSBio-294 dose presented the best results, without significant difference from standard treatment with dexamethasone at 2 mg/kg. This was the chosen dose for the remaining trials, in which we could see that the treatment with LASSBio-294 was also able to decrease the concentration of myeloperoxidase,

malondialdehyde, restore colonic levels of glutathione, along with the reduction of pro- inflammatory cytokine IL-1β e TNFα, in addition to the reduction of iNOS expression,

comparing this group to the one that received only acetic acid rectally. From the previous results, it can be inferred that LASSBio-294 decreased the inflammatory response in the colitis model experimentally induced by acetic acid, and may represent a promising therapeutic alternative for patients with ulcerative colitis.