Effect of Lead Exposure on the Activity of Some Hepatic Enzymes in the Rat

Abstract

SummarySeven-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 f 0.3 vs. 4.3 f 0.3, P < 0.001), and was maximal after 7 days of treatment (7.5 f 0.4 vs. 4.6 f 0.4, P < 0.001). GGTP activity was already maximally increased after 2 days of lead treatment (1.4 rt: 0.2 vs. 0.4 f 0.1, P < 0.001). Hepatic GT and GGTP activities were similarly increased in adult rats (7.9 f 0.3 vs. 5.1 f 0.1, P < 0.001, and 0.7 f 0.1 vs. 0.4 f 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. SpeculationThe 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.While lead remains one of the more important industrial and environmental toxins, and a series of recent factors have reduced the incidence of lead exposure and toxicity (1 I), its affect on the liver has received relatively little attention when compared to its impact on hematopoietic and neuromuscular systems. Lead administration to animals causes changes in the liver (12, 14) visible by light and electron microscopy. Additionally, it increases the concentrations of enzymes in serum released from damaged hepatocytes, and produces alterations in hepatocyte function as manifested by decreased bilirubin clearance and enhanced bromosulfophthalein retention (8,31). Recently, inhibition of the microsoma1 hepatic cytochrome P-450 dependent mixed function oxidase system has been reported (3, 26) in lead intoxicated animals and humans, suggesting the possibility of an alteration in hepatic drug metabolism. In order to explore further the effects of lead on hepatic enzyme activity, microsomal, noncytochrome P-450 dependent systems were studied in rats previously shown to be poisoned by lead (17). MATERIALS A N D METHODSanimals and littermate controls at 2,4, and 7 days were 12, 10; 8, 6; and 20, 18, respectively. All animals were killed by decapitation 24 hr after the last dose. The livers were removed, weighed, and the activity of UDP-bilirubin GT (EC 2.4.1.17), GGTP (EC 2.3.2.2), and hepatic protein content were determined. CHRONIC ADULT EXPOSUREFifteen adult male Sprague Dawley rats weighing 200-250 g were given a 1% lead acetate tetrahydrate solution in their daily drinking water for 6-8 wk. The lead solution was offered ad libitum. At the end of the treatment period, the rats were killed by decapitation, the livers were removed, weighed, GT and GGTP ...

Co-administration of sodium arsenite and ethanol: Protection by aqueous extract of Aframomum longiscapum seeds

“…SA and simultaneous administration of EtOH significantly ( P < 0.05) increased hepatic γ-GT activity in serum by about two- and threefold compared with the control [Table 4], this is inductive of hepatotoxicity and oxidative peroxidation in the hepatocyte cell membrane. Increased γ-GT activity in serum has been associated with hepatotoxicity,[44] chromosomal aberrations,[45] and oxidative stress in cells. [46] In the group treated with SA, EtOH and AL , the level of γ-GT activity decreased significantly ( P < 0.05) when compared with SA alone, SA and EtOH-treated rats.…”