Effect of lead exposure on the activity of some hepatic enzymes in the rat

Seven-day-old rats were fed 1% lead acetate tetrahydrate solution for 2, 4, or 7 days. Adult rats were fed the same lead solution for 6-8 wk. In the newborn rats, hepatic UDP-bilirubin glucuronyl transferase (GT) and gamma glutamyl transpeptidase (GGTP) activities were markedly increased. GT activity was increased after 4 days as compared to the controls (6.3 ± 0.3 vs. 4.3 ± 0.3, P < 0.001), and was maximal after 7 days of treatment (7.5 ± 0.4 vs. 4.6 ± 0.4, P < 0.001). GGTP activity was already maximally increased after 2 days of lead treatment (1.4 ± 0.2 vs. 0.4 ± 0.1, P < 0.001). Hepatic GT and GGTP activities were similarly increased in adult rats (7.9 ± 0.3 vs. 5.1 ± 0.1, P < 0.001, and 0.7 ± 0.1 vs. 0.4 ± 0.1, P < 0.005, respectively). In vitro studies adding lead citrate to liver homogenates did not produce any direct effect on GT and GGTP activities. The increase in hepatic GT and GGTP activities in lead treated animals appears to be a response to lead induced cellular damage or may result from interference with regulatory mechanisms responsible for production of these enzymes and not related to hepatic enzyme induction. The hepatic metabolism of drugs ingested by children with an increased lead burden may, therefore, be significantly altered.