Avaliação do papel da crotoxina na modulação da carcinogênese pulmonar induzida em animais fenotipicamente selecionados para a resposta inflamatória aguda

Abstract

Cancer is the main cause of death in the world, with lung cancer being responsible for most of the deaths, either because it is often diagnosed at a late stage or due to the lack of effective therapeutic methods. Crotoxin (CTX) is the main component of South American rattlesnake venom, corresponding to about 60% of its composition. In recent years, its immunomodulatory, anti-inflammatory, and antitumor properties have been described, making it a new possible candidate for therapeutic use. In order to study the regulatory role of CTX, lung carcinogenesis was induced by intraperitoneal injection of urethane (URT) in mice phenotypically selected for maximal (AIRmax) or minimal (AIRmin) acute inflammatory responses. From a genetic background, these animals have different sensitivity to urethane-induced lung tumorigenesis due to the fixation of alleles with opposite effects at the pas1 locus (Pulmonary adenoma susceptibility 1) during the selection process, with a susceptibility allele (pas1s ) in the

AIRmin mice and a resistance allele (pas1r

) in the AIRmax mice. Considering these differences and the described effects of CTX, these animals were subjected to different treatments with CTX and evaluated regarding their tumorigenesis in terms of incidence and cellular dynamics in the lung. The results showed that the phenotypes of resistance and susceptibility in the mice were preserved, even after CTX administration. Additionally, possible modulatory effects of CTX were observed, mainly in histopathologic analysis on the groups where CTX was administered 10 days after tumor induction by urethane with a concentration of 8 μg/kg and 16 μg/kg, and also on the treatment where CTX was administered every 10 days with a concentration of 8 μg/kg.