Effects of fasting on cadmium toxicity, glutathione metabolism, and metallothionein synthesis in rats.

Acute oral toxicity of Cd (as cadmium chloride) was enhanced in rats fasted 24 hr, as shown by a markedly decreased LD50. To examine the relationship among Cd toxicity, hepatic glutathione (GSH), and metallothionein (MT) during fasting, rats were administered 75 mg Cd/kg orally 24 hr after fasting and euthanized after a further 4 or 24 hr for various assays. Serum glutamic-pyruvic transaminase activity 24 hr after Cd treatment was higher in fasted rats than in fed rats. Both total GSH and nonprotein sulfhydryl (NPSH) concentrations in liver decreased to 50% of control levels after 28 hr of fasting and returned to 75% of control values by 48 hr. Total hepatic GSH concentration in fed rats decreased 4 and 24 hr after Cd treatment, whereas that in fasted rats remained unchanged at 4 hr and decreased significantly at 24 hr. Cd uptake by the liver (both concentration and content) 24 hr after Cd treatment was higher in fasted rats than in fed rats. Hepatic MT concentration was markedly increased by Cd treatment and higher in fasted rats than in fed rats. There was no relationship between Cd toxicity and hepatic thiobarbituric acid (TBA) value, an indicator of lipid peroxidation. Fasting had no effect on hepatic GSH peroxidase and GSH reductase activities. These enzymes probably are not involved in Cd toxicity. On histological examination, focal degenerative and necrotic changes were observed from the midlobular to the pericentral region in the livers of fed rats 24 hr after Cd treatment. These changes were enhanced by fasting, diffusing from the pericentral to the periportal region. Histochemical examination revealed a heterogeneous distribution of GSH in the livers of fed rats, with strong staining of GSH in the periportal region. This heterogeneous distribution of GSH in liver was not observed in fed rats 4 hr after Cd treatment or in fasted rats at 24 hr. The present results suggest that hepatic GSH plays an important role in protection against Cd toxicity before the onset of MT synthesis. Animals in bad condition, such as that resulting from interruption of nutrient supply, cannot be protected against Cd toxicity even if the hepatic MT level is high.