Impacto sistêmico do envenenamento por Bothrops jararaca na função testicular

Abstract

Brazil has a high incidence of snakebite accidents, primarily involving snakes of the Bothrops genus, making necessary the search for more effective treatments with fewer side effects than the currently available antivenom serum. Literature studies show that in cases of envenomation, bothropic venom causes an intense inflammatory response and local and systemic hemorrhages, effects that may be related to proteolytic proteins of the venom, such as serine and metalloproteases (SVSPs – Snake Venom Serine Proteases and SVMPs – Snake Venom Metalloproteases). Although it is well established that bothropic envenomation causes clinical manifestations in sites distant from the bite, such as cardiovascular shock and acute renal failure, the implications of this condition on the male reproductive system need to be further investigated. Thus, this work analyzed the modulation of the testicular proteome of mice after experimental envenomation with Bothrops jararaca venom, as well as the effect of administering an endogenous metalloprotease inhibitor in this model. Using label-free LC-MS/MS, the results showed an increase in the abundance of proteins related to inflammation, apoptosis, and oxidative stress in the testicles of animals that received the bothropic venom injection. Proteomic analyses revealed that envenomation modulates the abundance of proteins associated with sperm motility and the regulation of male fertility, indicating possible impairment of testicular function. The obtained results indicate that the venom may disrupt the blood-testis barrier and dysregulate essential cellular processes, impacting tissue homeostasis and impairing male reproductive capacity. The administration of the endogenous metalloprotease inhibitor actinonin did not mitigate the effects caused by B. jararaca venom. Therefore, new studies are needed to characterize the action of this inhibitor in testicular tissue, for the development of therapeutic strategies that could be associated with bothropic antivenom for treating the systemic effects caused by snakebite accidents with B. jararaca. This is the first study in the scientific literature that verified, through the proteomic signature of testicular tissue in a murine model, the deleterious effects of bothropic envenomation on the integrity and functionality of male reproductive tissue.