title: Tissue-specific induction and inactivation of cytochrome P450 catalysing lauric acid hydroxylation in the sea bass, Dicentrarchus labrax.
abstract: Microsomal cytochrome P450-dependent lauric acid hydroxylase activities were characterized in liver, kidney, and intestinal mucosa of the sea bass (Dicentrarchus labrax). Microsomes from these organs generated (omega-1)-hydroxylauric acid and a mixture of positional isomers including (omega)-, (omega-2)-, (omega-3)- and (omega-4)-hydroxylauric acids, which were identified by RP-HPLC and GC-MS analysis. Peroxisome proliferators, such as clofibrate and especially di(2-ethylhexyl) phthalate, increased kidney microsomal lauric acid hydroxylase activities. The synthesis of 11-hydroxylauric acid was enhanced 5.3-fold in kidney microsomes. Liver microsomal lauric acid hydroxylase activities were weakly affected and no significant induction was found in small intestine microsomes from clofibrate or di(2-ethylhexyl) phthalate-treated fish. The differences in lauric acid metabolisation and the tissue-specific induction by peroxisome proliferators suggest the involvement of several P450s in this reaction. Incubations of liver and kidney microsomes with lauric acid analogues (11- or 10-dodecynoic acids) resulted in a time- and concentration-dependent loss of lauric acid hydroxylase activities. The induction of these activities in fish by phthalates, which are widely-distributed environmental pollutants, may be taken into consideration for the development of new biomarkers.
mesh_terms: D000818:Animals; D001492:Bass / Q000378:metabolism*; D015415:Biomarkers; D002994:Clofibrate / Q000494:pharmacology; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D006900:Hydroxylation; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D007850:Lauric Acids / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D009928:Organ Specificity; D020025:Peroxisome Proliferators / Q000494:pharmacology*; D013379:Substrate Specificity