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Metabolism of n-hexane by rat liver and extrahepatic tissues and the effect of cytochrome P-450 inducers

Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle NE2 4HH, UK

PG Blain

Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle NE2 4HH, UK

Faith M Williams

Department of Environmental and Occupational Medicine, The Medical School, University of Newcastle upon Tyne, Newcastle NE2 4HH, UK

1 The in vitro metabolism ofn-hexane was studied in rat liver, lung, brain and skeletal muscle microsomes and in microsomes prepared from cell lines expressing human cytochrome P-450 2E1 or 2B6. The hydro xylated metabolites ofn-hexane were quantified by gas chromatography-mass spectometry.

2 Rat liver and extensor digitorum longus (EDL, fast- twitch skeletal muscle) microsomes and the CYP 2B6 microsomes produced the pre-neurotoxic metabolite of n-hexane, 2-hexanol as a major metabolite in contrast to the other rat tissues examined.

3 Inhibition of 2- and 3-hexanol production from n- hexane by rat lung microsomes using metyrapone, an inhibitor of cytochrome P-450 2B1 activity, resulted in almost complete inhibition of lung microsomal activ ity.

4 Production of all three hexanols was significantly increased with phenobarbital-induced rat liver micro somes, with a 10-fold increase in 2- and 3-hexanol production. A slight increase in 2-hexanol production with phenobarbital-induced rat EDL and brain micro somes was observed. No increase in n-hexane meta bolism was noted following induction with β- naphthoflavone or with ethanol.

Key Words: n-Hexane • skeletal muscle • cytochrome P-450 • extra hepatic metabolism

Human & Experimental Toxicology, Vol. 16, No. 3, 131-137 (1997)
DOI: 10.1177/096032719701600301


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