Precision-Cut Liver Slices of Salmo salar as a tool to investigate the oxidative impact of CYP1A-mediated PCB 126 and 3-methylcholanthrene metabolism

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• 作者：Benjamin Lemaire^a ; ^b ; Michaë ; l Beck^a ; ^b ; Mé ; lanie Jaspart^d ; Cathy Debier^a ; ^b ; Pedro Buc Calderon^c ; ^e ; Jean-Pierre Thomé ; ^d ; Jean-Franç ; ois Rees^a ; ^b ; ^{jf.rees@uclouvain.be}
• 关键词：Precision-Cut Liver Slices ; CYP1A induction ; Oxidative stress ; Antioxidant enzymes ; 3-Methylcholanthrene ; PCB 126
• 刊名：Toxicology in Vitro
• 出版年：2011
• 出版时间：February 2011
• 年：2011
• 卷：25
• 期：1
• 页码：335-342
• 全文大小：302 K

文摘

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 doseȁ3;response analysis (25ȁ3;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 H₂O₂ production, antioxidant enzymes activities or oxidative damage to lipids were found with 3-MC treatments. PCLS subjected to PCB 126 (2ȁ3;200 nM) showed increased contamination levels and a parallel increased CYP1A mRNA synthesis and EROD activity. H₂O₂ 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.