Male Sprague-Dawley rats (three per treatment group) were administered 0, 2, 10, 20, or 40 mg aluminum per kilogram ip per day for 3 days as aluminum chloride in saline. Animals were killed 24 hr later. Aluminum was found to inhibit hepatic drug metabolism in a dose-dependent fashion. The lowest dose (2 mg or 75 μmol/kg) had no effect on the parameters measured, whereas the highest dose (40 mg or 1.5 mmol/kg) caused a 52% decrease in cytochrome P-450, a 71% decrease in p-nitrophenetole O-deethylase activity, and a 77% decrease in ethylmorphine N-demethylase activity. Hepatic glutathione levels were unaffected by aluminum, whereas metallothionein (MT) was induced in both liver and kidney. The distribution of endogenuous metals normally associated with MT was altered by aluminum administration. At the highest dose of aluminum (40 mg/kg), zinc levels were increased in liver cytosol (154%), while copper levels were unchanged in liver, but decreased in kidney (70%). Aluminum was present in the liver and kidney. Of the aluminum in the liver, less than 5% was in the cytosol, bound to a MT-like protein. It is concluded that acute ip administration of aluminum adversely effects hepatic drug metabolism and that aluminum induces and binds to MT or a MT-like protein.
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