EFFECT OF SEVERAL METALLOTHIONEIN INDUCERS ON OXIDATIVE STRESS DEFENSE-MECHANISMS IN RATS

One mechanism by which chemicals cause cellular injury is the formatio n of reactive oxygen species. In vitro studies have shown that metallo thionein (MT), a small metal-binding, sulfhydryl-rich, readily inducib le protein, can scavenge reactive oxygen species, especially hydroxyl radicals. Nevertheless, whether or not MT protects against oxidative s tress in the intact animal is not known, Experimental induction of MT could help to clarify this question, however, it is unclear whether ag ents that induce MT also influence known antioxidant systems. Therefor e, the present study was designed to determine whether the well-known MT inducers are specific for induction of MT or whether they might als o influence other hepatic systems that protect against oxidative stres s. Male rats were administered cadmium chloride (Cd; 30 mu mol/kg, s.c ,), zinc chloride (Zn; 1000 mu mol/kg, s.c.), alpha-hederin (alpha-H, 30 mu mol/kg, s.c.) or lipopolysaccharide (LPS; 1 mg/kg, s,c.) 24 h pr ior to measurement of antioxidant systems. Zn and alpha-H increased he patic GSH concentration 20% and 55%, respectively. Cd significantly in creased, whereas LPS reduced, the activities of selenium-dependent glu tathione peroxidase and glutathione reductase. Glutathione S-transfera ses were not altered by any of the inducers. Cd also increased DT-diap horase activity. Cd, Zn and alpha-H all decreased catalase activity 20 -35%, while the activity of superoxide dismutase was unaffected by the inducers. The amount of total cytochrome P450 enzymes and cytochrome b(5) were decreased by LPS, Cd and alpha-H, while Zn appeared to have no effect. The activities of P450 enzymes towards testosterone oxidati on were also decreased by LPS, Cd and alpha-H. In conclusion, all four MT inducers examined affect systems known to protect cells against ox idative stress. Therefore, using these chemicals to determine the in v ivo role of MT in protecting against oxidative stress poses difficulti es.