Avaliação da atividade pró-inflamatória de Bothropstoxina-I do veneno de Bothrops jararacussu em camundongos AIRmax e AIRmin.

Abstract

Snakebites are characterized as a neglected disease worldwide. Envenomation by snakes of the Bothrops genus have been mostly studied, due to their prevalence and incidence of related accidents. Hemorrhage, edema, tissue damage, myonecrosis; in addition to systemic effects, such as renal failure and incoagulability are described in bothropic envenomation. Local inflammatory effects are evident and mainly correlated with the tissue damage triggered by the toxins from the whole venom. The in vitro experimental model of C2C12 myoblasts has been a tool to study the myotoxicity induced by distinct toxins as well as the repair and regeneration processes. Metalloproteinases are predominant among other components in most of Bothrops snakes, however, for the Bothrops jararacussu, phospholipases A2 (PLA2) are in greater quantity. This finding may be mainly related to the high myotoxicity verified in the envenomation involving this snake. B. jararacussu venom has two main PLA2: bothropstoxin-I and II (BthTX-I and BthTX-II, respectively). BthTX-I is a PLA2 Lys49 with a molecular mass of 13.7kDa that has a myotoxic and pro-inflammatory effect on site of the bite. In this work, we aimed to obtain the BthTX-I from the whole venom and to study the pro-inflammatory potential using in vivo and in vitro experimental models. For this, in in vivo model we evaluated the myotoxic action of BthTX-I in mice selected for high and low acute inflammatory response - AIRmax and AIRmin, respectively, and evaluated the ability of the toxin to induce the IL-1β and IL -6 production by peritoneal macrophages from these mice. Furthermore, we evaluated the myotoxic action of BthTX-I on differentiated C2C12 myotubes in vitro. The BthTX-I induced myotoxicity in AIRmax and AIRmin mice and the production of IL-1β and IL -6 by macrophages primed with LPS. In cultures of C2C12 myotubes, we observed morphological alterations of the fibers induced by the toxin.