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Current Topics in Medicinal Chemistry

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Research Article

Renal Alterations Induced by the Venom of Colombian Scorpion Centruroides Margaritatus

Author(s): J.D. Galíndez-Cerón, R.J.B. Jorge*, M.H. Chavez-Acosta, A.R.C. Jorge, N.T.Q. Alves, M.M.G. Prata, F.A. de Paulo Rodrigues, A. Havt, T.L. Sampaio, A.M.C. Martins, J.A. Guerrero-Vargas, H.S.A. Monteiro and J.T. Beltrán-Vidal

Volume 19, Issue 22, 2019

Page: [2049 - 2057] Pages: 9

DOI: 10.2174/1568026619666190731143523

Price: $65

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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.

Keywords: Scorpion envenomation, Centruroides margaritatus, Kidney perfusion, Cytotoxicity, Necrosis, Acute kidney injury.

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