Look what you make my tissues do: The role of metalloproteinases and their inhibitors in Bothrops snakebites

Background Bothrops envenomation induces extensive local tissue destruction and a robust inflammatory response, largely driven by the host’s endogenous molecular pathways. Among these, Matrix Metalloproteinases (MMPs), zinc-dependent endopeptidases responsible for extracellular matrix (ECM) degradation, play a central role. The clinical severity of envenomation is therefore strongly influenced by the balance between MMPs and their specific inhibitors, the TIMPs. This study investigated the contribution of MMP-1, MMP-2, MMP-7, MMP-9, and MMP-10 and TIMP-1, TIMP-2, TIMP-3, and TIMP-4 to the inflammatory response following Bothrops snakebites. Methods and findings In this study, we prospectively enrolled 30 patients, classified them as Mild or Severe, and quantified circulating MMPs and TIMPs concentrations before and after antivenom administration using a multiplex Luminex platform. Early inflammatory markers and initial MMPs activation (MMP-2, MMP-7, MMP-9, MMP-10) did not differ significantly between groups. However, post-antivenom molecular trajectories diverged sharply. Mild cases exhibited effective enzymatic regulation, restoring the MMPs/TIMPs profile toward a state that favored ECM turnover and tissue repair. In contrast, Severe cases showed persistent dysregulation, with a sustained imbalance that hindered ECM reorganization and perpetuated damaging inflammatory pathways. Conclusion These findings suggest that the regulation of MMP/TIMP balance following antivenom therapy may be associated with clinical evolution. Further studies are required to determine whether these molecular patterns can be validated as prognostic markers or therapeutic targets.