由哥伦比亚玛格丽塔角蝰蝎毒液引起的肾脏改变。

Renal Alterations Induced by the Venom of Colombian Scorpion Centruroides Margaritatus.

机构信息

Departamento de Biología, Facultad de Ciencias Naturales, Exactas y de la Educación, Grupo de Investigaciones Herpetológicas y Toxinológicas, Universidad del Cauca, Popayán, Colombia.

Departamento de Fisiologia e Farmacologia, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE, Brazil.

出版信息

Curr Top Med Chem. 2019;19(22):2049-2057. doi: 10.2174/1568026619666190731143523.

DOI:10.2174/1568026619666190731143523

PMID:31364515

Abstract

BACKGROUND

Scorpion venom causes renal injury and affects vascular ion-channels function. Centruroides margaritatus scorpion is found in Colombia and is frequently the cause of envenomation accidents; however, its renal impact has never been investigated.

OBJECTIVE

To evaluate the effects of C. margaritatus venom (CmV) on renal parameters using isolated rat kidney and renal cell culture models.

METHODS

Wistar rats (n = 5, weighing 240-300 g) were first perfused with Krebs-Henseleit solution containing 6 g 100 mL-1 bovine serum albumin. After 30 minutes, the kidneys were perfused with CmV to a final concentration of 10 μgmL-1; evaluation was performed by measuring Perfusion Pressure (PP), Renal Vascular Resistance (RVR), Urinary Flow (UF), Glomerular Filtration Rate (GFR), and percentage of electrolyte tubular transport. Moreover, kidney histological analyses and cell cytotoxicity in renal tubule epithelial cells (MDCK) and proximal tubular cells (LLC-MK2) were assessed.

RESULTS

CmV increased PP and RVR 60 min after perfusion. On the other hand, UF, GFR, and the percentages of sodium, potassium and chloride tubular transport decreased after experimental envenomation. UF dropped after 120 min, while GFR and percentage of electrolyte tubular transport diminished after 60, 90 and 120 min. CmV was not toxic to MDCK cell line but reduced the viability of LLC-MK2 cells at concentrations ranging from 6.25 to 200 μgmL-1. Histological analyses disclosed hydropic degeneration, edema, and protein deposits. Flow cytometry disclosed that cell death occurred predominantly by necrosis.

CONCLUSION

Our results suggest that C. margaritatus venom can trigger renal impairment, mainly in the proximal kidney tubule.

摘要

背景

蝎子毒液会导致肾脏损伤，并影响血管离子通道功能。在哥伦比亚发现的加拉帕戈斯金蝎经常引发中毒事故；然而，其对肾脏的影响从未被研究过。

目的

使用分离的大鼠肾脏和肾细胞培养模型评估 C. margaritatus 毒液（CmV）对肾脏参数的影响。

方法

首先用含有 6 g 100 mL-1 牛血清白蛋白的 Krebs-Henseleit 溶液灌注 Wistar 大鼠（n = 5，体重 240-300 g）30 分钟。然后，将肾脏用终浓度为 10 μgmL-1 的 CmV 灌注；通过测量灌注压（PP）、肾血管阻力（RVR）、尿流量（UF）、肾小球滤过率（GFR）和电解质管状转运的百分比来进行评估。此外，还评估了肾组织学分析以及肾近端小管上皮细胞（MDCK）和肾近端小管细胞（LLC-MK2）的细胞毒性。

结果

CmV 灌注 60 分钟后增加了 PP 和 RVR。另一方面，UF、GFR 和钠、钾和氯的肾小管转运百分比在实验性中毒后下降。UF 在 120 分钟后下降，而 GFR 和电解质管状转运的百分比在 60、90 和 120 分钟时减少。CmV 对 MDCK 细胞系没有毒性，但在浓度范围为 6.25 至 200 μgmL-1 时降低了 LLC-MK2 细胞的活力。组织学分析显示水样变性、水肿和蛋白沉积。流式细胞术显示细胞死亡主要通过坏死发生。