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

CURRENT TOPICS IN MEDICINAL CHEMISTRY(2019)

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摘要
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 mu gmL(-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 mu gmL(-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.
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关键词
Scorpion envenomation,Centruroides margaritatus,Kidney perfusion,Cytotoxicity,Necrosis,Acute kidney injury
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