Polymyxin B Nephrotoxicity: From Organ to Cell Damage

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dc.contributor.author Fernandes Vattimo, Maria de Fatima
dc.contributor.author Watanabe, Mirian
dc.contributor.author da Fonseca, Cassiane Dezoti
dc.contributor.author de Moura Neiva, Luciana Barros
dc.contributor.author Pessoa, Edson Andrade [UNIFESP]
dc.contributor.author Borges, Fernanda Teixeira [UNIFESP]
dc.date.accessioned 2019-07-22T15:46:54Z
dc.date.available 2019-07-22T15:46:54Z
dc.date.issued 2016
dc.identifier http://dx.doi.org/10.1371/journal.pone.0161057
dc.identifier.citation Plos One. San Francisco, v. 11, n. 8, p. -, 2016.
dc.identifier.issn 1932-6203
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/51167
dc.description.abstract 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 en
dc.description.abstract 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. en
dc.description.sponsorship Fundacao de Amparo a Pesquisa do Estado de Sao Paulo
dc.description.sponsorship [2013/26560-2]
dc.description.sponsorship [2011/24028-6]
dc.format.extent -
dc.language.iso eng
dc.publisher Public Library Science
dc.rights Acesso aberto
dc.title Polymyxin B Nephrotoxicity: From Organ to Cell Damage en
dc.type Artigo
dc.description.affiliation Univ Sao Paulo, Sch Nursing, LEMA, Sao Paulo, Brazil
dc.description.affiliation Univ Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil
dc.description.affiliation Eneas Carvalho de Aguiar Ave 419, BR-05403000 Sao Paulo, Brazil
dc.description.affiliationUnifesp Univ Fed Sao Paulo, Div Nephrol, Sao Paulo, Brazil
dc.description.sponsorshipID FAPESP:2013/26560-2
dc.description.sponsorshipID 2011/24028-6
dc.identifier.file WOS000381487600057.pdf
dc.identifier.doi 10.1371/journal.pone.0161057
dc.description.source Web of Science
dc.identifier.wos WOS:000381487600057



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