The role of glutathione in the acute nephrotoxicity of sodium dichromate.
Ascorbate treatment 30 min prior to sodium dichromate (20 or 30 mg/kg, s.c.) shows higher potency than that of glutathione (GSH) in protecting against both the metabolic disturbance and nephrotoxicity induced by dichromate. However, ascorbate treatment after 2 h of dichromate intoxication had no effect on dichromate-induced blood urea nitrogen (BUN) elevation 3 days after intoxication. In contrast, dichromate-induced glucosuria, which reached maximum levels at 3 days after treatment, was significantly decreased by GSH or N-acetyl cysteine (NAC) treatment, even if its administration was after 24 h of dichromate intoxication. Pretreatment with GSH depletors such as diethyl maleate (DEM) and buthionine sulfoximine (BSO) had no effect on dichromate-induced nephrotoxicity. GSH levels in the liver and kidney were not affected at 3 h after dichromate treatment. However, dichromate significantly increased tissue GSH levels with a marked increase in liver per kidney GSH ratio at 24 h after treatment, if food was withheld subsequent to dichromate treatment, indicating that GSH biosynthesis resulted from the accelerated protein breakdown. These results suggest that GSH-mediated dichromate reduction is not a kinetically favorable pathway in vivo; however, GSH plays an important role in protection against dichromate-induced nephrotoxicity. In addition, the cellular metabolism of dichromate in the early period after treatment is important in the pathogenesis of its nephrotoxicity.
Na
K J
KJ
Korea Ginseng and Tobacco Research Institute, Taejon.
Jeong
S Y
SY
Lim
C H
CH
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002840:Chromates / Q000378:metabolism / Q000633:toxicity*; D005978:Glutathione / Q000494:pharmacology / Q000502:physiology*; D007668:Kidney / Q000473:pathology; D007674:Kidney Diseases / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D002840:Chromates; D013438:Sulfhydryl Compounds; C016104:sodium bichromate; D005978:Glutathione; D001205:Ascorbic Acid