Cadmium potentiation of drug response—Role of the liver

Johnston, R.E.; Miya, Tom S.; Schnell, R.

doi:10.1016/0006-2952(75)90158-6

Cited by 38 publications

(7 citation statements)

References 19 publications

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“…Potentiation of drug response mechanisms in the liver has been shown at 2 mg Kg-1 cadmium acetate intraperitoneally in mice (Hadley & Miya, 1972) and rats (Johnson, Miya & Schnell, 1975). Changes have also been reported in carbohydrate metabolism, although acute exposure to cadmium did not change activities of hepatic gluconeogenic enzymes (Singhal & Merali, 1979).…”

Section: Cardiovascular Systemmentioning

confidence: 94%

Teratogenicity, Toxicity and Perinatal Effects of Cadmium

et al. 1982

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Section: Cardiovascular Systemmentioning

confidence: 94%

Teratogenicity, Toxicity and Perinatal Effects of Cadmium

et al. 1982

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“…Potentiation of hexobarbital sleep time and inhibition of hepatic drug-metabolizing enzymes have been observed after acute Cd2+ administration to animals (22)(23)(24)(25). On the contrary, Wagstaff (26) has reported a stimulatory effect of dietary Cd2+ on hepatic microsomal drug metabolism.…”

Section: Discussionmentioning

confidence: 99%

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.

Morita¹

1984

Jpn.J.Pharmacol

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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

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“…It is this cumulative nature of Cd that makes it potentially toxic at low environmental concentrations [2]. Interaction of cadmium with drugs may involve both an alteration in drug disposition and a change in liver response, and this can be accomplished by investigating the alterations in disposition and metabolism of a xenobiotic after exposure to cadmium [3]. The effect of exposure of both HCH and Cd on the metabolism of HCH has not been described in the literature.…”

Section: Introductionmentioning

confidence: 98%

Influence of cadmium on the storage and metabolism of HCH in rats

Khanna

Gupta

Anand

1999

Toxicological & Environmental Chemistry

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Male albino rats were administered Cd and HCH daily for six weeks to study the effect of Cd on storage and metabolism of HCH. The results indicated a marked inhibition of the metabolism of HCH in the group dosed with HCH + Cd. The metabolic rate of HCH in the group dosed with HCH + Cd was also significantly lower than that in the group dosed with HCH alone. The hepatic content of Cd and Zn was significantly increased whereas a marked depletion of Cu and Fe was observed in the groups exposed to Cd and HCH + Cd. A high level of free Cd and Zn or a low level of Fe and Cu in liver seemed to play an important role in the metabolic inhibition observed in this study.

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Cadmium potentiation of drug response—Role of the liver

Cited by 38 publications

References 19 publications

Teratogenicity, Toxicity and Perinatal Effects of Cadmium

Teratogenicity, Toxicity and Perinatal Effects of Cadmium

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.

Influence of cadmium on the storage and metabolism of HCH in rats

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