Ontogenic changes in the nephrotoxicity of chromate correlate with the glutathione oxidoreduction system.
The role of GSH concentration and GSSG reductase activity in age differences in chromate nephrotoxicity was investigated. Young and adult rats were injected with 2 and 1 mg sodium chromate/100 g body weight (BW), respectively, which led to equal Cr concentrations in renal tissue. Cr nephrotoxicity was lower in young than in adult rats. It was shown that from 30 minutes after the chromate injection GSSG reductase activity in renal tissue was increased in adult but decreased in young rats by the chromate. GSSG reductase activity was increased in young rats by pretreatment with phenobarbital. The consequence was an enhancement of chromate nephrotoxicity as shown by proteinuria. Renal GSH concentration is lower in young rats and limiting for chromate reduction in vitro in these animals. Therefore, GSH concentration was increased by pretreatment with N-acetylcysteine, which enhanced chromate nephrotoxicity significantly. These results reflect the important role of the GSH oxidoreduction system in chromate nephrotoxicity and its relationship to age differences.
Appenroth
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Institute of Pharmacology and Toxicology, Friedrich Schiller University, Jena, Fed. Rep. of Germany.
D000111:Acetylcysteine / Q000494:pharmacology; D000375:Aging / Q000378:metabolism; D000818:Animals; D002840:Chromates / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D054477:Glutaredoxins; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D010088:Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology; D011490:Protein Disulfide Reductase (Glutathione); D011507:Proteinuria / Q000652:urine; D051381:Rats; D017670:Sodium Compounds / Q000008:administration & dosage / Q000633:toxicity*
D002840:Chromates; D054477:Glutaredoxins; D017670:Sodium Compounds; C028982:sodium chromate(VI); D010088:Oxidoreductases; C020667:glutathione oxidase; D011490:Protein Disulfide Reductase (Glutathione); D005978:Glutathione; D000111:Acetylcysteine; D010634:Phenobarbital