Avaliação da atividade anti-inflamatória da BmooMP-alfa-l, uma metaloprotease isolada da peçonha da serpente Bothrops moojeni, em modelo de ileite induzida por Toxoplasma gondii

Abstract

Inflammatory bowel diseases (DIIs) are chronic immune mediated diseases. DIIs are divided into ulcerative colitis and Crohn’s disease. Also, DIIs are extremely debilitating for patients. The exacerbated production of TNF cytokine is related to the intestinal damage during Crohn’s disease and the neutralization of this cytokine has been suggested as a therapeutic intervention. Oral infection by Toxoplasma gondii induces intestinal inflammation through the overproduction of TNF, which is quite similar to the response during Crohn’s disease. BmooMP-a-I is a snake venom metalloprotease isolated from Brothrops moojeni, which is able to cleave TNF. Considering these pieces of information, we aimed to evaluate whether the treatment with BmooMP-a-I can reduce the deleterious effect of the T. gondii-induced ileitis. For this purpose, we induced ileitis in C57BL/6 mice by oral infection with 50 cysts of T. gondii. The animals were treated with BmooMP- a-I or inoculated with PBS as control and tissue samples were collected on day 7 postinfection to evaluate the metalloprotease effects on treated animals. Indices of morbidity and mortality were determined in addition to the cytokine profile production. It was observed that BmooMP-a-I treatment increased the survival rates of the infected animals, as well as reduced clinical signs of the survivals, particularly weight loss. Moreover, the metalloprotease treatment ameliorates the macroscopic and microscopic aspect of intestine. The treatment also reduced proinflammatory cytokine production and expression of inflammatory mediators by mesenteric lymph node cells. Additionally, occurred a reduction of ex vivo response of spleen and mesenteric lymph node cells. Overall, these findings constitute strong evidence that the BmooMP-a-I treatment is able to reduce ileal inflammation, making possible to hypothetize that this type of approach could be also helpful for treating of other inflammatory bowel diseases, such as Crohn’s disease.