Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Gentamicin-induced preconditioning of proximal tubular LLC-PK1 cells stimulates nitric oxide production but not the synthesis of heat shock protein

Autor Pessoa, Edson de Andrade Autor UNIFESP Google Scholar
Convento, Marcia.Bastos Autor UNIFESP Google Scholar
Silva, Ronaldo Goncalves da Autor UNIFESP Google Scholar
Oliveira, Accary Souza Bulle Autor UNIFESP Google Scholar
Borges, Fernanda Teixeira Autor UNIFESP Google Scholar
Schor, Nestor Autor UNIFESP Google Scholar
Instituição Universidade Federal de São Paulo (UNIFESP)
Resumo Nephrotoxicity is the main side effect of antibiotics such as gentamicin. Preconditioning has been reported to protect against injuries as ischemia/reperfusion. The objective of the present study was to determine the effect of preconditioning with gentamicin on LLC-PK1 cells. Preconditioning was induced in LLC-PK1 cells by 24-h exposure to 2.0 mM gentamicin (G/IU). After 4 or 15 days of preconditioning, cells were again exposed to gentamicin (2.0 mM) and compared to untreated control or G/IU cells. Necrosis and apoptosis were assessed by acridine orange and HOESCHT 33346. Nitric oxide (NO) and endothelin-1 were assessed by the Griess method and available kit. Heat shock proteins were analyzed by Western blotting. After 15 days of preconditioning, LLC-PK1 cells exhibited a significant decrease in necrosis (23.5 ± 4.3 to 6.5 ± 0.3%) and apoptosis (23.5 ± 4.3 to 6.5 ± 2.1%) and an increase in cell proliferation compared to G/IU. NO (0.177 ± 0.05 to 0.368 ± 0.073 µg/mg protein) and endothelin-1 (1.88 ± 0.47 to 2.75 ± 0.53 pg/mL) production significantly increased after 15 days of preconditioning compared to G/IU. No difference in inducible HSP 70, constitutive HSC 70 or HSP 90 synthesis in tubular cells was observed after preconditioning with gentamicin. The present data suggest that preconditioning with gentamicin has protective effects on proximal tubular cells, that involved NO synthesis but not reduction of endothelin-1 or production of HSP 70, HSC 70, or HSP 90. We conclude that preconditioning could be a useful tool to prevent the nephrotoxicity induced by gentamicin.
Palavra-chave Pre-conditioning
Gentamicin
Nitric oxide
LLC-PK1 cells
Acute kidney injury
Apoptosis
Idioma Inglês
Data de publicação 2009-07-01
Publicado em Brazilian Journal of Medical and Biological Research. Associação Brasileira de Divulgação Científica, v. 42, n. 7, p. 614-620, 2009.
ISSN 0100-879X (Sherpa/Romeo, fator de impacto)
Publicador Associação Brasileira de Divulgação Científica
Extensão 614-620
Fonte http://dx.doi.org/10.1590/S0100-879X2009005000005
Direito de acesso Acesso aberto Open Access
Tipo Artigo
Web of Science WOS:000267703600005
SciELO S0100-879X2009000700005 (estatísticas na SciELO)
Endereço permanente http://repositorio.unifesp.br/handle/11600/5129

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