Lead toxicity as related to glutathione metabolism.
The effect of lead poisoning on glutathione metabolism was studied in rat pups born of dams receiving a commercial laboratory diet supplemented with 0.5% lead acetate. Results showed that the body weight gain of the first 3 weeks of life and at the age of 6 weeks was significantly less in both male and female pups nourished by lead-fed dams than those raised by dams receiving the lab diet. Lead ingestion decreased hematocrit levels and hemoglobin values and increased the weights of liver, kidney, spleen and brain. Concentrations of plasma free histidine, glutamic acid and serine were decreased in lead-poisoned rats but glycine levels were markedly increased. After 4 weeks of lead feeding, both sexes had an increased glutathione concentration in erythrocytes, liver and kidney. Isotope studies further indicated that the incorporation of cystine-35S was significantly increased in glutathione but decreased in protein of liver and kidney of lead-fed rats. Similarly, lead ingestion significantly increased glycine-1-14C incorporation into renal glutathione. However, the activities of glutathione reductase and glutathione peroxidase were unaffected by lead poisoning. The data suggest a compensatory mechanism operates to overcome the toxicity of ingested lead by maintaining a high concentration of glutathione in the liver and kidney.
D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D001835:Body Weight / Q000187:drug effects*; D005260:Female; D005978:Glutathione / Q000378:metabolism*; D005979:Glutathione Peroxidase / Q000378:metabolism; D005980:Glutathione Reductase / Q000378:metabolism; D006400:Hematocrit; D006454:Hemoglobins / Q000378:metabolism; D007774:Lactation; D007855:Lead Poisoning / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D051381:Rats; D012737:Sex Factors
D000596:Amino Acids; D006454:Hemoglobins; D005979:Glutathione Peroxidase; D005980:Glutathione Reductase; D005978:Glutathione