Effect of several metallothionein inducers on oxidative stress defense mechanisms in rats.

One mechanism by which chemicals cause cellular injury is the formation of reactive oxygen species. In vitro studies have shown that metallothionein (MT), a small metal-binding, sulfhydryl-rich, readily inducible protein, can scavenge reactive oxygen species, especially hydroxyl radicals. Nevertheless, whether or not MT protects against oxidative stress in the intact animal is not known. Experimental induction of MT could help to clarify this question, however, it is unclear whether agents that induce MT also influence known antioxidant systems. Therefore, the present study was designed to determine whether the well-known MT inducers are specific for induction of MT or whether they might also influence other hepatic systems that protect against oxidative stress. Male rats were administered cadmium chloride (Cd; 30 mumol/kg, s.c.), zinc chloride (Zn; 1000 mumol/kg, s.c.), alpha-hederin (alpha-H, 30 mumol/kg, s.c.) or lipopolysaccharide (LPS; 1 mg/kg, s.c.) 24 h prior to measurement of antioxidant systems. Zn and alpha-H increased hepatic GSH concentration 20% and 55%, respectively. Cd significantly increased, whereas LPS reduced, the activities of selenium-dependent glutathione peroxidase and glutathione reductase. Glutathione S-transferases were not altered by any of the inducers. Cd also increased DT-diaphorase 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 b5 were decreased by LPS, Cd and alpha-H, while Zn appeared to have no effect. The activities of P450 enzymes towards testosterone oxidation were also decreased by LPS, Cd and alpha-H. In conclusion, all four MT inducers examined affect systems known to protect cells against oxidative stress. Therefore, using these chemicals to determine the in vivo role of MT in protecting against oxidative stress poses difficulties.

Effect of selenium on plasma glucose of rats: role of insulin and glucocorticoids.

The effects of acute treatment (i.p.) of selenium (Se) on glucoregulation and on plasma levels of glucose, insulin and corticosterone were determined in both fed and 24-hour-fasted rats. In this experiment animals were treated with saline (control) or 1.3, 1.6 and 3.8 mg/kg doses of Se. Blood samples were collected before, 30, 60 and 90 min following injection. The results obtained show that acute intraperitoneal (i.p.) administration of Se (1.6 mg/kg or more) causes hyperglycemia in rats. It was found that Se does not change levels of plasma insulin in either fasted or fed animals. Se did, however, significantly increase the plasma levels of corticosterone in all Se-treated groups. In order to confirm the role of corticosterone and thus support the significance of adrenal glands in this hyperglycemic response, animals were subjected to bilateral adrenalectomy. Blood samples were collected before, 30, 60 and 90 min following intraperitoneal treatment with Se. The results indicate that bilateral adrenalectomy abolishes the hyperglycemic response to Se. It can be concluded that adrenal glands play a role in Se-induced hyperglycemia. The increase in corticosterone levels suggest the possibility of gluconeogenesis in contributing to this hyperglycemic response.