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Pretreatment of rats with acetylsalicylic acid or sodium salicylate stimulates the metabolism of dichloromethane to carbon monoxide as measured by the carboxyhemoglobin level in blood. Simultaneous administration of dichloromethane and acetylsalicylic acid or sodium salicylate, respectively, was accompanied by reduced carboxyhemoglobin formation. In liver microsomes of rats pretreated with acetylsalicylic acid the p-nitrophenol hydroxylase activity was increased. It is concluded that (i) cytochrome P-450 2E1 is involved in the metabolic conversion of both dichloromethane and salicylic acid, and (ii) salicylic acid may be an inducer of cytochrome P-450 2E1.

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1 The metabolism of dichloromethane (DCM) to carbon monoxide as measured by the carboxyhaemoglobin (COHb) level in the blood is stimulated by pretreatment with methanol (MET). After simultaneous administration of both DCM, 6.2 mmol kg-1 p.o., and MET, > 148 mmol kg-1 p.o., the COHb formation is inhibited. 2 MET ingestion results in a transient decrease of the glutathione (GSH) content of the liver. In rats treated with GSH-depleting chemicals such as diethylmaleate (DEM), phorone (PHO), or buthionine sulphoximine (BSO) there were no enhancements of the carboxyhaemoglobinaemia caused by DCM. The COHb formation was not influenced by an increase of the hepatic GSH concentration due to repeated administration of butylated hydroxyanisole (BHA). 3 It is concluded that cytochrome P450 IIEl (CYP 2E1) is responsible for the metabolic interaction of both DCM and MET, and MET may be an inducer of CYP 2E 1. The two pathways of DCM, the oxidative via CYP 2E l and the metabolism via GSH/GSH-S-transferase seem to be independent.

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