Abstract
Lead ingestion produces profound alterations in liver morphology and enzyme levels, as well as plasma protein composition in newborn rats. Seven day old rats were given 0.5ml 1% lead acetate by gastric tube daily × 7 and sacrificed. When compared to littermate controls, lead resulted in significant weight loss (19.6 ± 3.5 vs 24.3 ± 2.0gm) (m ± SD); anemia (Kct 24.2 ± 1.9 vs 31.3 ± 4.4%); kidney enlargement (0.37 ± 0.08 vs 0.28 ± 0.07gm); and encephalopathy (cerebellar hemorrhage). Examination of liver showed no change in liver weight, protein content or DNA and RNA synthesis (3H-thymidine and uridine incorporation). Hepatic UDP-glucuronyl transferase(GT) activity increased 69% in the lead treated newborn rats (1662 ± 301 vs 982 ± 207μM bilirubin/gm/40min). Lead treated adult rats showed a similar significant increase in GT activity (1864 ± 122 vs 1181 ± 172μM/gm/40min). Likewise γ-glutamyl trans-peptidase activity was significantly increased in both newborn and adult rats. Analysis of plasma proteins showed a lead induced increase of 84% in albumin (2.3 ± 0.7 vs 1.3 ± 0.5gm/dl);116% increase in transferrin (12.1 ± 1.9 vs 5.6 ± 2.2mg/ml); and 74% decrease in hemopexin (0.51 ± 0.38 vs 1.96 ± 0.88mg/ml). Morphologically, lead produced ultrastructural alterations in endoplasmic reticulum and the appearance of lamellar membranous bodies. GT is a membrane-bound enzyme which is activated by sulfhydryl-blocking agents and phospholipases. Lead, by binding to sulfhydryl groups and disrupting microsomal membranes may exert similar metabolic effects by “unmasking” active enzyme sites.
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Kochen, J., Muller-Eberhard, U., Cohen, M. et al. METABOLIC EFFECTS OF LEAD IN NEWBORN RATS. Pediatr Res 11, 417 (1977). https://doi.org/10.1203/00006450-197704000-00290
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DOI: https://doi.org/10.1203/00006450-197704000-00290