Phospholipase A from venom induces acute kidney injury: involvement of ion channels in an isolated perfused rabbit kidney model.

BACKGROUND

Acute kidney injury (AKI) is a serious complication associated with envenomation, primarily due to direct nephrotoxicity. This study aimed to investigate the effects of the phospholipase A (RvPLA₂) fraction from 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 ( < 0.05), while non-significant increases were observed in glomerular filtration rate (GFR), urinary flow rate (UF), osmolar clearance (C), and the fractional excretion of sodium (FE) and potassium (FE). Verapamil alone caused significant increases in GFR and C ( < 0.05) and non-significant increases in PP, RVR, UF, FE, 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 RvPLA activity requires Ca for activation which may target distinct sites on the cell membrane, including ion channel receptors in nephrons. The effects of RvPLA on glomerular and renal tubular function are independent and cannot be modified by pretreatment with different ion channel blockers.