Influence of metyrapone and phenobarbital on sodium dichromate nephrotoxicity in developing rats

Appenroth, Dorothea; Gambaryan, Stepan; Friese, Klaus; Bräunlich, H

doi:10.1002/jat.2550100314

Cited by 8 publications

(2 citation statements)

References 18 publications

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“…This enhanced chromate toxicity might be a result of increased endoplasmic chromium(V1) metabolism. It is known that phenobarbital enhances chromate-induced kidney toxicity (Appenroth et al 1990), which is in agreement with our results from combining chromate exposure with acetone + fasting regarding liver toxicity. It might also be speculated that enhanced toxicity is due to glutathione depletion which is usually associated with fasting in rats (Brooks & Pong 1981).…”

Section: B Antibody Against P450iieisupporting

confidence: 93%

Effect of in Vivo Chromate, Acetone and Combined Treatment on Rat Liver in Vitro Microsomal Chromium(VI) Reductive Activity and on Cytochrome P450 Expression

Mikalsen¹,

Alexander²,

Andersen³

et al. 1991

Pharmacology & Toxicology

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Cytochrome P450 (P450IIE1) in rat has previously been shown to exhibit high chromate [Cr(VI)] reductase activity (Mikalsen et al. 1991). The present study reports on the effect of chromate treatment in vivo in rats and on the modulating effect of acetone+fasting on chromium(VI) toxicity. No effect of intraperitoneal injection with 5 mg chromate/kg was observed, whereas 15 mg chromate/kg decreased the liver microsomal Cr(VI) reductase activity by about 30% in in vitro microsomal incubations. In addition, the P450 and cytochrome b5 contents were decreased by about 30% and 25% respectively. Acetone+fasting caused increases of total microsomal P450 and cytochrome b5 contents, associated with similar increases in apoproteins P450IIE1 and P450IIB1+2, and their corresponding mRNA, and apoprotein NADPH‐P450 reductase, as well as NADPH‐P450 reductase and microsomal Cr(VI) reductive activities. Related to acetone+fasting alone, when given in combination with chromate (15 mg/kg) the Cr(VI) reductive activity was decreased by about 30%, associated with decreases in the P450 and cytochrome b5 contents, 65% and 35% respectively. This further reduced the apoprotein levels of P450IIB1+2, P450IIE1, and NADPH‐P450 reductase to 90%, 60%, and 40%, respectively, and the mRNA levels of P450IIB2 and P450IIE1. No effect was observed on NADPH‐P450 reductase activity. This dose also caused some macroscopic alterations in the liver. In contrast, the P450IIE1 apoprotein level in the lung was apparently stabilized or even increased by chromate in rats treated with acetone+fasting. The results show that acetone+fasting causes induction of microsomal Cr(V) metabolism and increases chromium toxicity. Chromate does not induce its own metabolism in liver and interferes, probably in a complex way, with P450 enzymes and their gene expression, especially when induced.

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Section: B Antibody Against P450iieisupporting

confidence: 93%

Effect of in Vivo Chromate, Acetone and Combined Treatment on Rat Liver in Vitro Microsomal Chromium(VI) Reductive Activity and on Cytochrome P450 Expression

Mikalsen¹,

Alexander²,

Andersen³

et al. 1991

Pharmacology & Toxicology

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“…Induction of cytochrome P-450 with isopentanol dramatically increased Cr(VI)-induced DNA strand breaks in cultured chick embryo hepatocytes, although part of this increase was probably due to a simultaneous increase in hepatocyte GSH levels (9). Phenobarbital treatment increased Cr(VI)-induced nephrotoxicity of immature rats, while metyrapone treatment decreased Cr(VI)-induced nephrotoxicity in adult rats (49). However, it is not known whether or not the mechanism of Cr(VI)-mediated nephrotoxicity is related to the mechanism of Cr(VI)-induced genotoxicity.…”

Section: Reductive Metabolism Of Chromium(vi)mentioning

confidence: 99%

Is there a role for reactive oxygen species in the mechanism of chromium(VI) carcinogenesis?

Standeven

Wetterhahn²

1991

Chem. Res. Toxicol.

115

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The ambiguous effect of ascorbic acid on chromate induced proteinuria in rats

et al. 1994

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The influence of ascorbic acid (AA, 5 g/kg body weight) on chromate (Cr, 10 mg/kg) induced proteinuria, which is a sensitive parameter of its nephrotoxicity, was investigated in adult female Wistar rats. The concentrations of Cr and ascorbic acid (AA) were determined in renal tissue. Cr nephrotoxicity is related to its intracellular reduction from Cr(VI) to Cr(III). Proteinuria was completely prevented by enhancement of extracellular reduction of Cr(VI) to Cr(III) followed by rapid renal excretion when Cr and AA were given concomitantly. With an interval up to 1 h between Cr and AA, proteinuria was decreased probably by the radical scavenging function of AA. At an interval of 3 h AA enhanced Cr toxicity by increased intracellular Cr reduction. If the interval was increased to 5 h or if Cr was given 24 h after AA, no influence of AA could be detected. Our results confirm that AA is a very effective reductant of Cr which can influence Cr nephrotoxicity in very high concentrations. It depends on the interval between Cr and AA administration whether or not there is a beneficial effect of AA in Cr nephrotoxicity.

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Influence of metyrapone and phenobarbital on sodium dichromate nephrotoxicity in developing rats

Cited by 8 publications

References 18 publications

Effect of in Vivo Chromate, Acetone and Combined Treatment on Rat Liver in Vitro Microsomal Chromium(VI) Reductive Activity and on Cytochrome P450 Expression

Effect of in Vivo Chromate, Acetone and Combined Treatment on Rat Liver in Vitro Microsomal Chromium(VI) Reductive Activity and on Cytochrome P450 Expression

Is there a role for reactive oxygen species in the mechanism of chromium(VI) carcinogenesis?

The ambiguous effect of ascorbic acid on chromate induced proteinuria in rats

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