Protective effects of selenium on cadmium toxicity in rats: Role of altered toxicokinetics and metallothionein
- National Cancer Inst., Frederick, MD (United States)
Selenium prevents the toxicity of the carcinogenic metal cadmium through undefined mechanisms. In this study, the authors determined the effects of selenium on cadmium toxicokinetics and on the ability of cadmium to induce metallothionein, a metal-binding protein that is thought to confer tolerance to cadmium toxicity. To assess the acute protective effects of selenium, male Wistar (WF/NCr) rats were given selenium (as SeO[sub 2]; 10 [mu]mol/kg, sc) at [minus]24, 0, and +24 h relative to cadmium (as CdCl[sub 2]; 45 [mu]mol/kg, sc). Over a 14-d period this dose of cadmium killed 6 out of 10 rats, while 100% of the cadmium-treated rats given concurrent selenium treatments survived. The acute increases in testicular weight that were seen with cadmium, indicative of edematous damage, were also prevented by concurrent selenium treatments. Further studies assessed the distribution and excretion of cadmium and its ability to induce metallothionein in rats given 40 [mu]mol Cd/kg, sc, at time 0 and selenium (10 [mu]mol/kg, sc) at [minus]24 and 0 h. Selenium treatments enhanced cadmium accumulation at 24 h in the liver (23%), testes (145%), and epididymis (35%) but reduced renal accumulation by more than half. Urine samples, collected at 0-3, 3-6, and 6-24 h following cadmium administration, indicted a markedly reduced excretion of cadmium in selenium treated rats during all time periods. The synthesis of metallothionein was stimulated to a much lesser extent by cadmium in selenium-treated rat kidney (41% decrease) but was unaffected in liver. The levels of cadmium-binding proteins within the testes were markedly reduced by cadmium treatment, an effect unmodified by selenium treatments. These results suggest selenium prevents acute cadmium toxicity through a mechanism that does not involve induction of metallothionein and in spite of a markedly enhanced retention of cadmium. 50 refs., 1 fig., 4 tabs.
- OSTI ID:
- 6697021
- Journal Information:
- Journal of Toxicology and Environmental Health; (United States), Vol. 38:2; ISSN 0098-4108
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
CADMIUM
TOXICITY
RATS
TOLERANCE
SELENIUM
RESPONSE MODIFYING FACTORS
EXCRETION
LIVER
METALLOTHIONEIN
PROTEINS
TESTES
URINE
ANIMALS
BIOLOGICAL MATERIALS
BIOLOGICAL WASTES
BODY
BODY FLUIDS
CLEARANCE
DIGESTIVE SYSTEM
ELEMENTS
GLANDS
GONADS
MALE GENITALS
MAMMALS
MATERIALS
METALLOPROTEINS
METALS
ORGANIC COMPOUNDS
ORGANS
RODENTS
SEMIMETALS
VERTEBRATES
WASTES
550500* - Metabolism
551000 - Physiological Systems
560300 - Chemicals Metabolism & Toxicology