Protection of carbon tetrachloride-induced hepatotoxicity by zinc: role of metallothionein
Cagen, S.Z.; Klaassen, C.D.
Toxicology and Applied Pharmacology 51(1): 107-116
1979
ISSN/ISBN: 0041-008X PMID: 524364 Document Number: 148726
The dose-dependent release of Ala aminotransferase and Asp aminotransferase into plasma 24 h following various doses of CCl4 (i.p.) was markedly lower in rats pretreated for 3 days with ZnCl2 (150 .mu.mol/kg per day) than in control rats. Although this dose of Zn produced a 34% decrease in hepatic concentration of cytochrome P-450 and a 50% decrease in binding of 14C derived from 14CCl4 to hepatic microsomal protein and lipid in vitro, prior treatment with a single injection of zinc (250 .mu.mol/kg) resulted in protection against CCl4 toxicity without changing P-450 concentrations or 14C binding. Administration of a single dose (250 .mu.mol/kg) of Zn or pretreatment on 3 consecutive days with 150 .mu.mol/kg Zn produced a 700 or 1900% increase in hepatic concentration of metallothionein (MT), respectively. Following administration of 14CCL4 to Zn-treated rats, radioactivity was present in the same elution volume as MT following gel filtration (G-75) of liver cytosol. MT may protect against CCl4-induced liver damage by sequestering reactive metabolites of CCl4.