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The biotransformation of alcohol to acetaldehyde plays an important role in impairing cellular Mg^(2+) homeostasis and transport. We hypothesized that hepatic function may be related to the cellular and plasma Mg^(2+) homeostasis. Therefore, the influence of hepatic metabolizing enzyme inducers or diabetes on ethanol (EtOH)-induced Mg^(2+) extrusion was studied using the perfused rat livers. In the livers of rats fed phenobarbital sodium (a P450 B1 inducer), EtOH (a P450 E1 inducer) for 7 days or of alloxan-induced diabetic (induction of P450 E1) rats, the EtOH-induced Mg^(2+) extrusion was significantly reduced and accompanied by an increase in hepatic cytochrome P450 activity, indicating that the Mg^(2+) extrusion is directly modified by EtOH. The liver/body weight ratio was significantly increased in phenobarbital sodium-fed rats, but decreased in EtOH-fed and in the diabetic rats. However, EtOH -induced Mg^(2+) extrusion was markedly reduced in the presence of 4-methylpyrazole (a specific inhibitor of alcohol dehydrogenase and P450 E1) or chloramphenicol (a inhibitor of hepatic metabolizing enzyme) in the perfusion medium, indicating that conversion of EtOH to acetaldehyde is involved in EtOH-induced Mg^(2+) efflux. Our results suggest that the EtOH-induced Mg^(2+) efflux from liver can be regulated by hepatic metabolizing enzyme system.
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