Biotransformation and elimination of 1-nitropyrene in the isolated perfused lung: effects of pretreating rats with phenobarbitone, beta-naphthoflavone, benz(A)anthracene or their mixtures.
The isolated perfused rat lung (IPL) was perfused with 60 ml of recirculating Krebs-Ringer solution containing 150 micrograms of 1-nitropyrene (1-NP) for 1 h. The 1-NP was administered to the IPL by the intratracheal or intravascular route. At specific time points after 1-NP administration, perfusate samples were removed from the IPL and analysed for 1-NP and its metabolites by HPLC. Monohydroxynitropyrenes, dihydroxynitropyrenes and 1-NP were found to be present in the perfusate. The time course of 1-NP concentrations in the perfusate could be described by a one-compartment pharmacokinetic model. Pretreatment of rats with beta-naphthoflavone (BNF), benz(a) anthracene (BA) or a mixture of phenobarbitone (PB) and BNF (PB + BNF) significantly enhanced the metabolism of 1-NP and decreased the mean residence time (MRT) of 1-NP in the perfusate. Pretreatment of rats with these mixed-function oxidase inducers also increased significantly the absorption of 1-NP by the lung when it was administered intratracheally. In contrast, pretreatment of rats with PB did not appear to have any effect on the pharmacokinetics of 1-NP in the IPL.
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Department of Biological Sciences, Simon Fraser University, Burnaby, BC, Canada.
He
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Chui
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D000818:Animals; D001551:Benz(a)Anthracenes / Q000494:pharmacology; D001711:Biotransformation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000378:metabolism*; D008297:Male; D009153:Mutagens / Q000493:pharmacokinetics*; D010477:Perfusion; D010634:Phenobarbital / Q000494:pharmacology; D011721:Pyrenes / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D019324:beta-Naphthoflavone / Q000494:pharmacology
D001551:Benz(a)Anthracenes; D004791:Enzyme Inhibitors; D009153:Mutagens; D011721:Pyrenes; D019324:beta-Naphthoflavone; C030935:benz(a)anthracene; C032668:1-nitropyrene; D010634:Phenobarbital