Phospholipase A2 from Daboia siamensis venom induces acute kidney injury: involvement of ion channels in an isolated perfused rabbit kidney model

Le résumé fourni par la source

Background: Acute kidney injury (AKI) is a serious complication associated with Daboia siamensis envenomation, primarily due to direct nephrotoxicity. This study aimed to investigate the effects of the phospholipase A2 (RvPLA₂) fraction from D. siamensis venom on renal function and to assess whether pretreatment with ion channel blockers could mitigate these effects using an isolated perfused kidney (IPK) model. Methods: Twenty IPKs were allocated into five groups (n = 4 each): (1) RvPLA₂ in calcium-deficient modified Krebs-Henseleit solution (MKHS), (2) RvPLA₂ in standard MKHS, (3) RvPLA₂ following pretreatment with verapamil (a voltage-gated Ca²⁺ channel blocker), (4) RvPLA₂ following pretreatment with amiloride (a Na⁺ channel blocker), and (5) RvPLA₂ following pretreatment with minoxidil (a KATP channel opener). Renal function parameters were assessed accordingly. Results: Administration of 280 μg of RvPLA₂ in calcium-deficient MKHS caused no significant changes in renal function. In contrast, RvPLA₂ in standard MKHS (1.9 mM Ca²⁺) significantly increased perfusion pressure (PP), renal vascular resistance (RVR), and free water excretion (p < 0.05), while non-significant increases were observed in glomerular filtration rate (GFR), urinary flow rate (UF), osmolar clearance (Cosm), and the fractional excretion of sodium (FENa⁺) and potassium (FEK⁺). Verapamil alone caused significant increases in GFR and Cosm (p < 0.05) and non-significant increases in PP, RVR, UF, FENa⁺, and free water excretion. Amiloride and minoxidil alone did not alter renal function. Pretreatment with verapamil, amiloride, or minoxidil failed to prevent the renal functional changes induced by RvPLA₂. Conclusions: The RvPLA2 activity requires Ca2+ for activation which may target distinct sites on the cell membrane, including ion channel receptors in nephrons. The effects of RvPLA2 on glomerular and renal tubular function are independent and cannot be modified by pretreatment with different ion channel blockers.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.