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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Polymyxin B Nephrotoxicity: From Organ to Cell Damage

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Fernandes Vattimo, Maria de Fatima ; Watanabe, Mirian ; da Fonseca, Cassiane Dezoti ; de Moura Neiva, Luciana Barros ; Pessoa, Edson Andrade ; Borges, Fernanda Teixeira
Total Authors: 6
Document type: Journal article
Source: PLoS One; v. 11, n. 8 AUG 17 2016.
Web of Science Citations: 17

Polymyxins have a long history of dose-limiting toxicity, but the underlying mechanism of polymyxin B-induced nephrotoxicity is unclear. This study investigated the link between the nephrotoxic effects of polymyxin B on renal metabolic functions and mitochondrial morphology in rats and on the structural integrity of LLC-PK1 cells. Fifteen Wistar rats were divided into two groups: Saline group, rats received 3 mL/kg of 0.9% NaCl intraperitoneally (i.p.) once a day for 5 days; Polymyxin B group, rats received 4 mg/kg/day of polymyxin B i.p. once a day for 5 days. Renal function, renal hemodynamics, oxidative stress, mitochondrial injury and histological characteristics were assessed. Cell membrane damage was evaluated via lactate dehydrogenase and nitric oxide levels, cell viability, and apoptosis in cells exposed to 12.5 mu M, 75 mu M and 375 mu M polymyxin B. Polymyxin B was immunolocated using Lissamine rhodamine-polymyxin B in LLC-PK1 cells. Polymyxin B administration in rats reduced creatinine clearance and increased renal vascular resistance and oxidative damage. Mitochondrial damage was confirmed by electron microscopy and cytosolic localization of cytochrome c. Histological analysis revealed tubular dilatation and necrosis in the renal cortex. The reduction in cell viability and the increase in apoptosis, lactate dehydrogenase levels and nitric oxide levels confirmed the cytotoxicity of polymyxin B. The incubation of LLC-PK1 cells resulted in mitochondrial localization of polymyxin B. This study demonstrates that polymyxin B nephrotoxicity is characterized by mitochondrial dysfunction and free radical generation in both LLC-PK1 cells and rat kidneys. These data also provide support for clinical studies on the side effects of polymyxin B. (AU)

Grantee:Mirian Watanabe
Support Opportunities: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 13/26560-2 - Iodinated contrast induced acute kidney injury in diabetic and nephropathy diabetic in rats
Grantee:Maria de Fatima Fernandes Vattimo
Support Opportunities: Regular Research Grants