초록
Several metabolic modulators on the generation of carbon monoxide (CO)from dichloromethane (DCM) was examined in adult female rats. It has been known that DCM is converted to CO by cytochrome P-450 or to carbon dioxide $(CO_2)$ by glutathione-dependent metabolic reaction. In rats treated with DCM (3 mmol/kg, ip) only, the carboxyhemoglobin (COHb) level reached a peak of approximately 10% 2 or 3 hr following the treatment. Disulfiram (300 mg/kg, ip) or allylsulfide (200 mg/kg, po), both known as a selective inhibitior for cytochrome P-450 2E1, blocked the increase in COHb concentratlons almost completely suggesting that the metabolic conversion of DCM to CO is mediated by the activity of this specific type of isozyme. YH439 (125 or 250 mg/kg, po), a potential hepatoprotective agent, decreased the COHb elevation as well indicating that this chemical is a potent inhibitor for 2E1. In rats treated with pyrazine (200 mg/kg, ip) 18 hr prior to DCM the peak COHb concentration was decreased by approximately 3 or 4%. However, pretreatment of rats with pyrazine either 24 or 48 hr before DCM increased the peak COHb concentration significantly compared to the rats treated with DCM only. The results in the present study strongly suggest that the generation of CO from DCM depends on the 2E1 activity and that the pharmacological and/or toxicological action of YH439 or pyrazine in animals or human is associated with its effect on this isozyme.