Chaiyabutr Narongsak, Vasaruchapong Taksa, Laoungbua Panithi, Khow Orawan, Chanhome Lawan, Sitprija Visith
Queen Saovabha Memorial Institute, Thai Red Cross Society, Pathumwan, Bangkok, Thailand.
Snake Farm, Queen Saovabha Memorial Institute, Thai Red Cross Society, Bangkok, Thailand.
J Venom Anim Toxins Incl Trop Dis. 2025 Aug 4;31:e20250016. doi: 10.1590/1678-9199-JVATITD-2025-0016. eCollection 2025.
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.
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.
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.
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.
急性肾损伤（AKI）是与蛇咬伤相关的一种严重并发症，主要由于直接肾毒性所致。本研究旨在探讨毒液中的磷脂酶A（RvPLA₂）组分对肾功能的影响，并使用离体灌注肾（IPK）模型评估用离子通道阻滞剂预处理是否可以减轻这些影响。
将20个IPK分为五组（每组n = 4）：（1）在缺钙改良Krebs-Henseleit溶液（MKHS）中加入RvPLA₂；（2）在标准MKHS中加入RvPLA₂；（3）用维拉帕米（一种电压门控Ca²⁺通道阻滞剂）预处理后加入RvPLA₂；（4）用阿米洛利（一种Na⁺通道阻滞剂）预处理后加入RvPLA₂；（5）用米诺地尔（一种KATP通道开放剂）预处理后加入RvPLA₂。相应地评估肾功能参数。
在缺钙MKHS中给予280μg RvPLA₂对肾功能无显著影响。相比之下，标准MKHS（1.9 mM Ca²⁺）中的RvPLA₂显著增加灌注压（PP）、肾血管阻力（RVR）和自由水排泄（<0.05），而肾小球滤过率（GFR）、尿流率（UF）、渗透清除率（C）以及钠（FE）和钾（FE）的分数排泄有非显著增加。单独使用维拉帕米可使GFR和C显著增加（<0.05），PP、RVR、UF、FE和自由水排泄有非显著增加。单独使用阿米洛利和米诺地尔不改变肾功能。用维拉帕米、阿米洛利或米诺地尔预处理未能预防RvPLA₂诱导的肾功能变化。
RvPLA活性需要Ca激活，其可能作用于细胞膜上不同位点，包括肾单位中的离子通道受体。RvPLA对肾小球和肾小管功能的影响是独立的，且不能通过用不同离子通道阻滞剂预处理来改变。
