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.

Abstract

Abstract-Resistanceto 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.Pretreatment of animals with small doses of certain metals protects against subsequent toxic doses of the same metals (1-5). It has been proposed that protection by Cd2+ pretreatment against a lethal dose of the cation is due to the induction of metallothionein (MT) synthesis (4, 6-8). However, Webb and Verschoyle (3) have suggested that pre-induced MT may not be the only factor giving protection against the toxic action of Cd2+. As these investigations (2-8) were performed by parenteral administration of the test metal, the interaction of the metal with intestinal tissue was not studied.In my preliminary study (unpublished data), oral LD50 values for cadmium chloride, cupric chloride, ferrous sulfate, ferric chloride, mercuric chloride, manganese chloride, lead nitrate and zinc sulfate were determined in female ICR mice pretreated orally with single small doses (1/10 of the challenge doses) of the same cations or with deionized water 24 hr prior to the challenge doses. Among the eight metal salts tested, Cd2+ pretreatment gave the most effective protection against the acute oral toxicity of the same cation as evidenced by an increased LD50. Therefore, the present study was designed with oral administration of Cd2+ to mice to examine the effects of time intervals between

Protective Effect of Curcumin on Anxiety, Learning Behavior, Neuromuscular Activities, Brain Neurotransmitters and Oxidative Stress Enzymes in Cadmium Intoxicated Mice

“…The major target organs that are reported for the acute oral toxicity of Cd are liver [46] and central nervous tissue [47]. Cd has been recognized as one of the most toxic environmental and industrial pollutants that may induce oxidative damage by disturbing the prooxidant-antioxidant balance in the tissues.…”

Isolation of novel metal-binding proteins distinct from metallothionein from spotted seatrout (Cynoscion nebulosus) and Atlantic croaker (Micropogonias undulatus) ovaries

“…Tolerance has been demonstrated towards cadmium-induced lethality (Probst et al 1977, Baer andBenson 1987), inhibition of hepatic drug metabolism (Roberts and Schnell 1982), hepatic necrosis (Morita 1984) and teratogenicity (Layton and Ferm 1980). MT may function in the homeostasis of essential heavy metals, specifically, zinc and copper (Reviewed in Cousins 1985).…”

Influence of Squid Liver Powder on Accumulation of Cadmium in Serum, Kidney and Liver of Mice

“…In addition, pathological symptoms of liver tissues were further degenerated on week 8 compared to week 4 regardless of whether lipids were removed because of liver toxicity and reduction in liver regeneration due to long-term exposure to cadmium. Morita (42) and Kudo et al (43) medicated high concentrations of cadmium in mice to observe liver cell necrosis, degeneration, cirrhosis, abnormal sinusoid structure, structural changes in Kupffer cells, and discoloration of dead cell nucleus. Such results are similar to the results of this study.…”