Avaliação dos efeitos cardiotóxicos do envenenamento loxoscélico experimental e seu tratamento com subprodutos de células-tronco mesenquimais

Abstract

The venom of spiders of the genus Loxosceles sp. can cause a clinical condition called loxoscelism, characterized by dermonecrosis, acute kidney injury, and other systemic disorders that can eventually lead to death. However, little is known about the cardiotoxic effects of loxoscelic venom. Furthermore, since there is no antidote available in veterinary medicine, the search for effective new therapies is imperative. Given this context, the present study aimed to evaluate the cardiotoxic effects of L. intermedia venom in guinea pigs (Cavia porcellus) and the use of secretome as a treatment for this envenomation. For this purpose, 28 healthy males were used and distributed into five groups: (A) challenged with 0.9% saline and treated with 0.9% saline; (B) challenged with 14µg of L. intermedia venom and treated with 0.9% saline; (C) challenged with 0.9% saline and treated with 160µg of secretome; (D), challenged with 14µg of L. intermedia venom and treated with 160µg of secretome; (E) - challenged with 14µg of L. intermedia venom and treated with 0.2mL of human antiloxoscelic serum (antivenom). For 14 days, the animals were evaluated by electrocardiogram, hematological, and plasma biochemical tests. After this period, the animals were euthanized for anatomohistopathological evaluation and isolation of cardiomyocytes for study of contractility and patch clamp (ex vivo). The results revealed that loxoscelic venom was able to interfere with cardiac activity, as it caused several arrhythmias in vivo and changes in cardiac contractility and action potential parameters (ex vivo). The deleterious effects of the venom on the heart may occur indirectly, such as changes in oxygenation and vascularization caused by the presence of clots, in addition to inflammatory processes, such as lymphoplasmacytic and lymphohistioplasmacytic infiltrates in the myocardium and endocardium, visualized under optical microscopy. Regarding the new therapy studied, the use of secretome at a dose of 160µg as a treatment for loxoscelism was not superior to the use of antivenom. However, when animals envenomed and treated with secretome were compared to animals treated with placebo (group B), the number of cardiac arrhythmias was much lower, which suggests the need for further studies to better characterize its composition and establish therapeutic doses.