Photobiomodulation attenuates BjussuMP-II-induced muscle inflammation: effects on leukocyte recruitment and MIR-223...

Bothrops jararacussu is one of the snake species most frequently involved in snakebite envenomation in Brazil. Snake venom metalloproteinases (SVMPs), which account for approximately 26.2% of its venom composition, play a central role in envenomation by inducing hemorrhage, myonecrosis, and a robust local inflammatory response. Although antivenom effectively neutralizes systemic toxicity, its efficacy against local tissue damage remains limited. In this context, the present study investigated the effects of 945 nm LED photobiomodulation on the inflammatory response induced by BjussuMP-II, a PI class SVMP isolated from B. jararacussu venom. Male Swiss mice (18-22 g) were administered BjussuMP-II (50 μg/animal) or PBS (50 μL) intramuscularly into the gastrocnemius muscle. Thirty minutes after BjussuMP-II administration, animals received antivenom, LED photobiomodulation, or combined treatment. Three hours later, histopathological analyses, intravital microscopy, miR-223 expression, and pro-inflammatory cytokine quantification were performed. Antivenom alone showed limited efficacy in controlling the inflammatory response induced by BjussuMP-II. In contrast, photobiomodulation, either alone or combined with antivenom, reduced inflammatory cell infiltration, leukocyte recruitment, leukocyte-endothelium interactions, and IL-6 levels, while modulating miR-223 expression. Collectively, these findings demonstrate that LED photobiomodulation exerts significant immunomodulatory effects on SVMP-induced inflammation and supports its potential as an adjunct to antivenom therapy for mitigating the local manifestations of Bothrops envenomation.