title: Interaction of metallothionein and carbon tetrachloride on the protective effect of zinc on hepatotoxicity.
abstract: To study the influence of hepatic metallothionein (MT) on the hepatotoxic response to carbon tetrachloride (CCl4), adult male rats were pretreated with a 10 mg X kg-1 dose of zinc (Zn) 24 h prior to CCl4 (i.p., l mL X kg-1) treatment. Zn pretreatment increased the hepatic MT concentrations markedly and reduced the magnitudes of the CCl4-induced reduction of cytochrome P450 concentration as well as elevation of serum alanine aminotransferase and aspartate aminotransferase activities when determined at 4 or 24 h following CCl4 treatment. Treatment of Zn-exposed animals with CCl4 also resulted in significant reduction of the concentrations of hepatic MT (as determined by the cadmium-saturation method) as well as cytosolic Zn. Sephadex G-75 chromatographic study of hepatic cytosols showed that MT-bound Zn was selectively depleted by CCl4 exposure. Moreover, it was demonstrated that CCl4, after metabolic activation, reduced the cadmium binding capacity of Zn-induced hepatic MT in vitro. To examine the possible protective effect of Zn independent of induction of MT synthesis, CCl4 was administered 2 h following Zn pretreatment and the hepatotoxic response was examined 4 h later. This study revealed limited protection by Zn prior to the induction of MT synthesis. These data further support a role of MT in the modulation of CCl4 hepatotoxicity.
mesh_terms: D000818:Animals; D002104:Cadmium / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning / Q000378:metabolism*; D056486:Chemical and Drug Induced Liver Injury; D003600:Cytosol / Q000378:metabolism; D066298:In Vitro Techniques; D008107:Liver Diseases / Q000378:metabolism* / Q000517:prevention & control; D008297:Male; D008668:Metallothionein / Q000096:biosynthesis* / Q000502:physiology; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D015032:Zinc / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D002104:Cadmium; D008668:Metallothionein; D015032:Zinc