Effect of several metallothionein inducers on oxidative stress defense mechanisms in rats
| Autor: | Marcus B. Iszard, Jie Liu, Curtis D. Klaassen |
|---|---|
| Rok vydání: | 1995 |
| Předmět: |
Lipopolysaccharides
Male Antioxidant medicine.medical_treatment Glutathione reductase Pharmacology Toxicology medicine.disease_cause Superoxide dismutase Rats Sprague-Dawley chemistry.chemical_compound Selenium Cytosol Cadmium Chloride Chlorides Cytochrome P-450 Enzyme System medicine Animals Testosterone Oleanolic Acid Dihydrolipoamide Dehydrogenase Glutathione Transferase chemistry.chemical_classification Reactive oxygen species Analysis of Variance Glutathione Peroxidase biology Superoxide Dismutase Glutathione peroxidase Glutathione Saponins Catalase Rats Oxidative Stress Cytochromes b5 Glutathione Reductase chemistry Biochemistry Liver Zinc Compounds biology.protein Carcinogens Metallothionein Oxidative stress Cadmium |
| Zdroj: | Toxicology. 104(1-3) |
| ISSN: | 0300-483X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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