Potencial terapêutico do colágeno extraído da pele de tilápia® na atenuação dos danos locais induzidos por veneno de Bothrops jararacussu: um estudo em camundongos Swiss

Abstract

Snakebite accidents are classified as a significant public health problem and have been included in the list of Neglected Tropical Diseases (NTDs) by the World Health Organization (WHO) (Silva et al., 2017). In the Americas, snakebite envenomation represents an important public health challenge, although on a smaller numerical scale compared to Afro-Asian regions. Many patients survive due to antivenom therapy; however, they are often left with permanent sequelae. In view of this reality, the World Health Organization officially included snakebite envenomation in the list of Neglected Tropical Diseases in 2017. Bothrops jararacussu belongs to the Viperidae family and is popularly known as jararacuçu; it is a highly dangerous venomous snake, standing out as the second largest venomous species in Brazil. Its venom causes extensive local damage, as it degrades components of the extracellular matrix of various tissues and the basement membranes of blood vessels. In this context, biomaterials capable of attenuating local tissue damage have been developed and investigated. Among these biomaterials, collagen extracted from tilapia skin stands out, presenting specific biochemical properties that make it a promising candidate for application in tissue repair therapies, especially in clinical contexts involving intense skin destruction. Thus, the therapeutic potential of collagen extracted from tilapia skin in attenuating the local effects induced by Bothrops jararacussu venom in Swiss mice was evaluated. The following procedures were performed: extraction and purification of tilapia skin collagen; collagen cytotoxicity testing; irritability assay using the chorioallantoic membrane (HET-CAM); in vivo experiments in Swiss mice; histological analysis using hematoxylin and eosin staining; mast cell evaluation using toluidine blue staining; and collagen fiber analysis using picrosirius red. The results demonstrated that collagen extracted from tilapia skin showed high biocompatibility and absence of cytotoxicity, in addition to stimulating cell proliferation in vitro. In the HET-CAM assay, collagen was classified as non-irritant and significantly reduced irritation induced by Bothrops jararacussu venom. In the in vivo assays, collagen significantly attenuated the formation and area of the hemorrhagic halo at all evaluated time points, although presenting a partial effect when compared to a metalloproteinase inhibitor. Histological analyses confirmed reduced hemorrhage, edema, myonecrosis, and inflammatory infiltrate in collagen-treated groups, with preservation of tissue structure. Additionally, collagen modulated the mast cell response and promoted recovery of the collagen matrix, restoring total collagen and type I collagen levels degraded by the venom. These findings indicate that tilapia skin collagen, in addition to mitigating the deleterious local effects of snake venom, exerts a protective action on injured tissue. Although further studies are necessary to evaluate the mechanisms of action, this biomaterial emerges as a promising alternative for the initial management of local effects of snakebite envenomation.