Polymyxin B Nephrotoxicity: From Organ to Cell Damage
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UNIFESP |
| Texto Completo: | http://dx.doi.org/10.1371/journal.pone.0161057 http://repositorio.unifesp.br/handle/11600/51167 |
Resumo: | 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 |
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Polymyxin B Nephrotoxicity: From Organ to Cell DamagePolymyxins 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 daysPolymyxin 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.Univ Sao Paulo, Sch Nursing, LEMA, Sao Paulo, BrazilUniv Fed Sao Paulo, Div Nephrol, Sao Paulo, BrazilEneas Carvalho de Aguiar Ave 419, BR-05403000 Sao Paulo, BrazilUniv Fed Sao Paulo, Div Nephrol, Sao Paulo, BrazilWeb of ScienceFundacao de Amparo a Pesquisa do Estado de Sao Paulo[2013/26560-2][2011/24028-6]FAPESP:2013/26560-22011/24028-6Public Library Science2019-07-22T15:46:54Z2019-07-22T15:46:54Z2016info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-http://dx.doi.org/10.1371/journal.pone.0161057Plos One. San Francisco, v. 11, n. 8, p. -, 2016.10.1371/journal.pone.0161057WOS000381487600057.pdf1932-6203http://repositorio.unifesp.br/handle/11600/51167WOS:000381487600057enginfo:eu-repo/semantics/openAccessFernandes Vattimo, Maria de FatimaWatanabe, Mirianda Fonseca, Cassiane Dezotide Moura Neiva, Luciana BarrosPessoa, Edson Andrade [UNIFESP]Borges, Fernanda Teixeira [UNIFESP]reponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2022-02-07T21:55:03Zoai:repositorio.unifesp.br/:11600/51167Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652022-02-07T21:55:03Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
| dc.title.none.fl_str_mv |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| title |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| spellingShingle |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage Fernandes Vattimo, Maria de Fatima |
| title_short |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| title_full |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| title_fullStr |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| title_full_unstemmed |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| title_sort |
Polymyxin B Nephrotoxicity: From Organ to Cell Damage |
| author |
Fernandes Vattimo, Maria de Fatima |
| author_facet |
Fernandes Vattimo, Maria de Fatima Watanabe, Mirian da Fonseca, Cassiane Dezoti de Moura Neiva, Luciana Barros Pessoa, Edson Andrade [UNIFESP] Borges, Fernanda Teixeira [UNIFESP] |
| author_role |
author |
| author2 |
Watanabe, Mirian da Fonseca, Cassiane Dezoti de Moura Neiva, Luciana Barros Pessoa, Edson Andrade [UNIFESP] Borges, Fernanda Teixeira [UNIFESP] |
| author2_role |
author author author author author |
| dc.contributor.author.fl_str_mv |
Fernandes Vattimo, Maria de Fatima Watanabe, Mirian da Fonseca, Cassiane Dezoti de Moura Neiva, Luciana Barros Pessoa, Edson Andrade [UNIFESP] Borges, Fernanda Teixeira [UNIFESP] |
| description |
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 |
| publishDate |
2016 |
| dc.date.none.fl_str_mv |
2016 2019-07-22T15:46:54Z 2019-07-22T15:46:54Z |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1371/journal.pone.0161057 Plos One. San Francisco, v. 11, n. 8, p. -, 2016. 10.1371/journal.pone.0161057 WOS000381487600057.pdf 1932-6203 http://repositorio.unifesp.br/handle/11600/51167 WOS:000381487600057 |
| url |
http://dx.doi.org/10.1371/journal.pone.0161057 http://repositorio.unifesp.br/handle/11600/51167 |
| identifier_str_mv |
Plos One. San Francisco, v. 11, n. 8, p. -, 2016. 10.1371/journal.pone.0161057 WOS000381487600057.pdf 1932-6203 WOS:000381487600057 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
- |
| dc.publisher.none.fl_str_mv |
Public Library Science |
| publisher.none.fl_str_mv |
Public Library Science |
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reponame:Repositório Institucional da UNIFESP instname:Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP |
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Universidade Federal de São Paulo (UNIFESP) |
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UNIFESP |
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UNIFESP |
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Repositório Institucional da UNIFESP |
| collection |
Repositório Institucional da UNIFESP |
| repository.name.fl_str_mv |
Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP) |
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biblioteca.csp@unifesp.br |
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1814268376115052544 |