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Effect of isoniazid or phenobarbital pretreatment on the metabolism of dihalomethanes to carbon monoxide.

Polish journal of occupational medicine and environmental health (1992-01-01)
D Pankow, M Weise, P Hoffmann
ABSTRACT

An oral dose of 6.2 mmoles of diachloromethane (DCM), bromochloromethane (BCM) or dibromomethane (DBM) per kg body mass yielded a maximum carboxyhemoglobin (COHb) level of about 9% (at 6 hr), 11% (at 8 hr) and 22% (at 12 hr), respectively. Pretreatment of rats with isoniazid, 4 x 0.36 mmol/kg i.p., produced significant enhancements of the COHb formation; the values were 18.0 +/- 0.8% COHb after DCM, 24.1 +/- 0.8% COHb after BCM, and 39.0 +/- 1.3% COHb after DBM. Prior administration of phenobarbital, 4 x 0.31 mmol/kg i.p., caused no appreciable alterations in the COHb levels after DCM and slight but significant increases after BCM as well as after DBM. The data indicate that the oxidative metabolism of dihalomethanes to carbon monoxide is mainly catalyzed by cytochrome P-450 IIE1 and that the DCM-evoked COHb formation seems to be a method of testing whether a chemical is an inducer of this form of cytochrome P-450 in vivo.

MATERIALS
Product Number
Brand
Product Description

Supelco
Bromochloromethane solution, certified reference material, 2000 μg/mL in methanol
Sigma-Aldrich
Bromochloromethane, contains 100 ppm BHT as inhibitor, ≥99.5%
Supelco
Bromochloromethane, analytical standard