Abstract
The effects of lead on the drug metabolizing system in liver microsomes and porphyrin metabolism in the bone marrow were studied using male Wistar rats (about 250 g in weight). To study the acute effects of lead, rats were given lead injection intraperitoneally once a day for three consecutive days at a dose of 0 (control), 0.1, 1.0, 10 or 50 mg/kg of lead in the form of lead acetate in a 5% glucose solution. In the 2nd experiment, the chronic effects of lead were studied by administering lead at a dose of 0 (control), 5 and 20 mg/kg once a week for 9 wk for a total of 10 administrations. After the last injection, each rat was fasted for 22 h in a metabolic cage to prevent the animal from eating bed chips or feces and was then sacrificed by decapitation. The rat liver microsome enzymes were used to evaluate the effects of lead on the hepatic functions.
In the acute stage, lead decreased the activities of drug metabolizing enzymes, such as aniline hydroxylase and aminopyrine N-demethylase, and decreased the contents of microsomal cytochrome P-450 and cytochrome b5. In the chronic stage, lead decreased the cytochrome P-450 and cytochrome b5 contents and induced hypertrophic liver, but did not affect the activity of aniline hydroxylase. These findings suggest that the rat gradually gained resistance against lead toxicity in the chronic stage.
In a supplementary experiment, lead was found to decrease the contents of heme in the microsome and to increase the activity of hemeoxygenase. The contents of heme-protein, such as cytochrome P-450 and cytochrome b5, were regulated not only by heme biosynthesis but also by heme degradation in the lead administered rats. Serum GPT and bilirubin showed no evident changes compared to the control in either the acute or the chronic stages in the hematological tests. Lead, however, increased total erythrocyte protoporphyrin (total EP) in rats administered lead for 9 wk in the chronic stage but not in those in the acute stage. The increase of total EP in the circulating blood might affect the life span of erythrocytes in the chronic stage.
