Immunopathophysiology, biochemistry, and clinical implications of Daboia siamensis venom: A possible challenge to macrophages' immunomodulation.

Daboia siamensis (Eastern Russell's viper) envenomation remains a major public health problem in Southeast Asia and is frequently associated with severe systemic complications, particularly coagulopathy and acute kidney injury (AKI). A complex mixture of biologically active toxins, including snake venom metalloproteinases (SVMPs), serine proteases (SVSPs), phospholipase A2 (PLA2), and other enzymes, synergistically disrupts vascular integrity, hemostasis, and organ microcirculation. Beyond the direct toxic effects of venom, secondary immune-mediated processes amplify tissue injury through endothelial activation, inflammatory mediators, and oxidative stress that contribute to microvascular dysfunction and ischemic injury, a major pathophysiology of AKI even after correction of systemic coagulation abnormalities. Although antivenom therapy remains the most effective treatment when administered early, its ability to prevent established organ damage is limited once tissue injury has occurred. Hence, immunomodulatory strategies targeting macrophage activation may be beneficial. This review integrates current knowledge on venom composition, immunopathophysiological mechanisms, and clinical manifestations of D. siamensis venom, with particular emphasis on factors contributing to renal injury. Improved understanding of the interconnected processes between venom and immune responses may support the development of adjunctive strategies to reduce organ complications and improve outcomes following Russell''s viper envenomation.