ISSN:
1432-0738
Keywords:
2-Methylpropene
;
Isobutene
;
2-Methyl-1,2-epoxypropane
;
Epoxides
;
Biotransformation
;
Liver
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Until now, no data are available concerning the biotransformation and toxicity of 2-methylpropene (or isobutene), a gaseous alkene widely used in industry (rubber, fuel additives, plastic polymers, adhesives, anti-oxidants). In this work, the biotransformation of 2-methyl-propene (MP) has been studied, using total liver homogenates of mice, supplemented with a NADPH-generating system. In analogy to other olefins, 2-methylpropene is metabolized to its epoxide 2-methyl-1,2-epoxypropane (MEP), as proved by the identification by gas chromatography coupled with mass spectrometry. The epoxidation is cytochromeP-450 dependent, as shown by experiments in the absence of the NADPH-generating system and in the presence of various concentrations of metyrapone and SKF 525-A, two known inhibitors of the mono-oxygenases. A simple gas chromatographic headspace method has been developed for the quantitative determination of the epoxide formed. The formation of MEP is never linear in function of time and it reaches a maximum after 20 min. Thereafter is decreases continuously to undetectable levels. This observation can be explained by the immediate action of epoxide hydrolase and glutathione S-transferase, converting the epoxide to 2-methyl-1,2-propanediol and to the glutathione conjugate respectively. The involvement of both enzymes has been demonstrated by the addition of 3,3,3-trichloropropene oxide and indomethacin. These inhibitors of, respectively, epoxide hydrolase and glutathione S-transferase increase the epoxide formation in a significant way. The actual concentration of MEP is therefore not only dependent on its formation by cytochromeP-450 dependent mono-oxygenases, but also on its conversion by epoxide hydrolase and glutathione S-transferase, both very active in liver tissue.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF01968959
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