Impacto das Metaloproteinases de Matriz, Inibidores Teciduais e Mediadores Imunológicos Solúveis Circulantes no Processo Inflamatório de Pacientes Vímas de Acidente Botrópico na Amazônia Brasileira

Abstract

The snake Bothrops atrox (B. atrox) is responsible for most reports of snakebite accidents in northern Brazil. The inflammatory reaction triggered by the venom is responsible for the clinical signs, with local and systemic effects observed in patients, in addition to their classification as mild, moderate and severe. The remodeling of the extracellular matrix (ECM) in these accidents is regulated by proteolytic enzymes such as matrix metalloproteinases (MMPs), and may be influenced by the inflammatory process. In this study, we evaluated for the first time the involvement of metalloproteinases (MMP1, MMP-2, MMP-7, MMP-9, MMP-10), TIMPs (TIMP-1, TIMP-2, TIMP-3 and TIMP-4) and inflammatory mediators (IL-1b, IL-6, TNF-alpha IL-10, IL-2 and IL-4) in patients who are victims of Bothrops snakebite accidents. This is an observational, longitudinal, and prospective study of patients who suffered Bothrops envenomation and sought care at the Fundação de Medicina Tropical Doutor Heitor Vieira Dourado (FMT-HVD). The study population was divided into 2 groups according to the signs and symptoms presented (mild and severe). Peripheral blood samples were collected at three time points: before serotherapy (T0), during (24h), and after serotherapy (48h). The study included a control group composed of individuals who had not suffered a previous snakebite. The quantification of the molecules was performed using the Luminex technique. Our results indicate that, in patients, there is a complex inflammatory response, with hematological changes that reflect the severity of the clinical picture. The correlation between cytokines and matrix metalloproteinases (MMPs) suggests a uniform initial inflammatory response, highlighting MMP-1 as a biomarker for severe cases. The elevation of inhibitors of metalloproteinases (TIMPs) indicates a regulatory response of the organism, while the progressive reduction of MMPs and TIMPs points to a physiological adaptation that stabilizes inflammation and promotes tissue recovery. These findings highlight the importance of monitoring MMPs and TIMPs as prognostic biomarkers and the need for therapeutic strategies that consider the complexity of the immune response, contributing to a more effective clinical management.