Estudo da ação modulatória da crotoxina em animais selecionados fenotipicamente para resposta inflamatória aguda submetidos à carcinogênese cutânea por 7,12 dimetilbenzantraceno

Abstract

The skin's immune system is made up of innate and adaptive immunity cells that act in defense against external agents, however, they can be affected when exposed to carcinogens such as polycyclic aromatic hydrocarbons (PAH), and suffer from their cytotoxic effects. An example of a PAH is 7,12 dimethylbenzanthracene (DMBA), which has toxic effects when interacting with the skin. Our analysis focused on the impacts of DMBA, alone or associated with TPA, on the skin of mice phenotypically selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response, in the face of the appearance of papillomatous lesions. Above all, we studied the influence of Crotoxin (CTX) or crude crotalic venom on the evolution of these lesions. In a first experiment, animals from both lines received the following treatments: acetone (control), DMBA 5x and CTX, evaluated for 80 days. In a subsequent protocol, we associated DMBA and TPA, with the following groups: acetone (control), DMBA/TPA, DMBA/TPA/CTX EPI 2x and DMBA/TPA/Poison evaluated for 7, 20, 80 and 120 days. A final two-stage protocol was carried out with CTX EPI applications 1x per week and subcutaneous administration equally at a time, and the animals were evaluated for periods of 20, 40 and 80 days. Our findings revealed that in the first protocol, AIRmin were more sensitive to DMBA, especially when considering the multiplicity and incidence of injuries. In the second protocol (DMBA/TPA), AIRmax exhibited a high incidence of lesions that resembled carcinomas, especially in the

groups that were exposed to CTX or poison. In the last approach, also with the two- stage protocol, we identified that the application of CTX EPI 1x per week inhibited the

progression of lesions in both lineages, something that was not evidenced with the subcutaneous administration of CTX. However, histopathological data suggest that the subcutaneous route of CTX administration is important in inhibiting malignant evolution. Additionally, by evaluating cell populations, we distinguished two subpopulations of Tγδ lymphocytes that may play an important role in tumor progression. This highlights the importance of CTX as an immunomodulatory agent in studies on sensitivity to HPA-type carcinogens.