Effects of Tetraethyl Lead on the Activities of Drug Metabolizing Enzymes in Different Tissues of the Rat

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Abstract
For several decades tetraethyl lead has been one of the most important organometallic compounds in commercial use. This organic derivative of lead is mainly used as an anti-knock agent added to petrol/gasoline. Subjects working in the manufacture and handling of petrol/gasoline are exposed to tetraethyl lead. The effects of tetraethyl lead on various drug metabolizing enzymes in different tissues of the rat are described. Tetraethyl lead was administered i.p. to rats (250 .mu.mol/kg) on 2 consecutive days. The animals were killed on day 3. Tetraethyl lead-treatment decreased the concentration of hepatic cytochrome P-450 (to 45% of the control), the hepatic activity of aryl hydrocarbon hydroxylase (to 41% of the control) and ethoxycoumarin deethylase (to 45% of the control). Epoxide hydratase activity was enhanced in the liver (1.3-fold), kidney (3.3-fold) and small intestinal mucosa (4.7-fold). The activity of glutathione S-transferase decreased in the liver (to 69% of the control) but increased in the kidney (1.5-fold) and small intestinal mucosa (1.7-fold). The glucuronidation of o-aminophenol was enhanced (2.2-fold) in the kidney of tetraethyl lead treated rats. Exposure to tetraethyl lead apparently brings about widespread changes in the ability of mammals to detoxify foreign compounds.