JVATiTD - Articles

Abstract

Background:  Envenomation by Daboia siamensis venom (RVV) can cause acute kidney injury (AKI), but its mechanisms remain unclear. Renal cell death via necrosis and apoptosis is central to AKI progression. Bax and Bcl-2 are key pro- and anti-apoptotic regulators and common markers of apoptosis; however, their roles in RVV-induced renal injury are poorly defined. Therefore, we investigated Bax and Bcl-2 gene expression and their ratio in AKI following the administration of RVV and its venom fractions. Methods:  Kidney tissue samples from intact rabbits (in vivo) and the isolated perfused kidney (IPK) model treated with RVV and its venom fractions (PLA₂, MP, LAAO, and PDE) were analyzed for Bcl-2 family expression at both mRNA and protein levels, together with histopathological evaluation. Bcl-2 and Bax mRNA expression was quantified by RT-qPCR using the ΔΔCt method, and protein expression was assessed by immunohistochemical analysis. Results:  Following the administration of RVV and its venom fractions, histopathological analysis revealed extensive tubulonephrosis across all renal tubular segments in both intact kidneys and the IPK model. In contrast, renal tubular necrosis involving all tubular segments occurred in the IPK model after exposure to the RVV, PLA₂ and MP fractions. Immunohistochemical analysis revealed a trend toward increased Bax protein expression and decreased Bcl-2 expression in multiple tubular segments compared to controls in both models. RT-qPCR analysis demonstrated a 1.5-fold upregulation of Bcl-2 and significant reductions in Bax expression and the Bax/Bcl-2 ratio (p < 0.05) in the IPK model relative to controls. Conclusions:  Envenomation with RVV and its venom fractions induced nephrotoxic acute kidney injury by modulating Bax- and Bcl-2-mediated apoptosis in renal tubular epithelial cells, with greater susceptibility observed in intact kidneys and a reduced apoptotic response in the IPK model. These findings suggest that prolonged venom exposure may be partially reversible or may shift cell-death signaling from apoptosis toward necrosis.

Keywords: Bcl-2 family; D. siamensis venom; Venom fractions; Apoptosis; Acute kidney injury (AKI)