Defense mechanisms against cadmium toxicity I. A biochemical and histological study of the effects of pretreatment with cadmium on the acute oral toxicity of cadmium in mice.
Resistance to the lethal action of Cd2+ produced in mice was maintained for 6 to 24 hr after pretreatment with 1/10 of the challenge Cd2+ doses as shown by an increased oral LD50. Pretreatment 24 hr prior to the challenge doses was most effective. In addition, 1/20 to 1/7 of the challenge doses was necessary to acquire the tolerance to the acute oral toxicity of Cd2+. The largest effect was found for pretreatment with 1/7 of the challenge doses. Acute liver injury at 24 hr after challenge with a large dose of Cd2+ (100 mg Cd2+/kg, p.o.) was markedly reduced by pretreatment with a small dose of the cation (15 mg Cd2+/kg, p.o.) 24 or 48 hr prior to the challenge dose as shown by a marked reduction in serum GOT and GPT activities and the reversal of histopathological changes. The elevated serum urea nitrogen at 4 hr after the Cd2+ challenge was reduced by pretreatment 6 to 24 hr prior to the challenge dose. In spite of the increased urea nitrogen 4 hr after the Cd2+ challenge, no morphological alterations were observed in the kidney at 24 hr. Serum Alp activity was not significantly influenced by the Cd2+ challenge. Glucose in serum was increased by the administration of a small dose of Cd2+, but was unaffected by a large dose. Decreases in hepatic RNA and DNA concentrations at 24 hr after the Cd2+ challenge were prevented by pretreatment 24 or 48 hr prior to the challenge dose. Potentiation of hexobarbital sleep time was observed at 6 or 24 hr after a small dose of Cd2+. Nevertheless, further potentiation at 24 hr after the Cd2+ challenge (75 mg Cd2+/kg, p.o., in this case) was reduced by pretreatment 24 hr prior to the challenge dose. A major target organ for the acute oral toxicity of Cd2+ was the liver rather than the kidney.
D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D001806:Blood Urea Nitrogen; D002104:Cadmium / Q000494:pharmacology*; D002105:Cadmium Poisoning / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004247:DNA / Q000378:metabolism; D004361:Drug Tolerance; D005260:Female; D006591:Hexobarbital / Q000494:pharmacology; D008099:Liver / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008813:Mice, Inbred ICR; D004364:Pharmaceutical Preparations / Q000378:metabolism; D011292:Premedication; D012313:RNA / Q000378:metabolism; D012890:Sleep / Q000187:drug effects
D004364:Pharmaceutical Preparations; D002104:Cadmium; D012313:RNA; D004247:DNA; D006591:Hexobarbital; D001219:Aspartate Aminotransferases