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Toxicol In Vitro ; 25(1): 335-42, 2011 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20946947

RESUMO

Fish isolated cell systems have long been used to predict in vivo toxicity of man-made chemicals. In present study, we tested the suitability of Precision-Cut Liver Slices (PCLS) as an alternative to these models that allows the evaluation of a global tissue response to toxicants, to investigate oxidative stress response to cytochrome P450 1A (CYP1A) induction in fish liver. PCLS of Salmo salar were exposed for 21 h to increasing doses of 3-methylcholanthrene (3-MC) and Polychlorobiphenyl 126 (PCB 126). 3-MC (25 µM) strongly induced CYP1A transcription. In dose-response analysis (25-100 µM), EROD activity was strongly increased at intermediate 3-MC concentrations. We found the counter-intuitive decline of EROD at the highest 3-MC doses to result from reversible competition with ethoxyresorufin. No increases of H(2)O(2) production, antioxidant enzymes activities or oxidative damage to lipids were found with 3-MC treatments. PCLS subjected to PCB 126 (2-200 nM) showed increased contamination levels and a parallel increased CYP1A mRNA synthesis and EROD activity. H(2)O(2) production tended to increase but no oxidative damage to lipids was found. As antioxidant enzymes activities declined at the highest PCB 126 dose, it is suggested that longer incubation periods could be required to generate oxidative stress in PCLS.


Assuntos
Citocromo P-450 CYP1A1/biossíntese , Fígado/efeitos dos fármacos , Metilcolantreno/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Bifenilos Policlorados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Citrato (si)-Sintase/metabolismo , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Indução Enzimática/efeitos dos fármacos , Peróxido de Hidrogênio/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/química , Fígado/metabolismo , Técnicas de Cultura de Órgãos , Concentração Osmolar , Oxirredutases/metabolismo , Bifenilos Policlorados/análise , RNA Mensageiro/metabolismo , Salmo salar , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fatores de Tempo , Testes de Toxicidade
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