ascorbic-acid has been researched along with 2-gluthionyl-3-5-6-trichloro-1-4-benzoquinone* in 2 studies
2 other study(ies) available for ascorbic-acid and 2-gluthionyl-3-5-6-trichloro-1-4-benzoquinone
| Article | Year |
|---|---|
The nephrotoxicity of 2,5-dichloro-3-(glutathion-S-yl)-1,4-benzoquinone, and 2,5,6-trichloro-3-(glutathion-S-yl)-1,4-benzoquinone is potentiated by ascorbic acid and AT-125.
Topics: Animals; Ascorbic Acid; Blood Urea Nitrogen; Chloranil; Drug Synergism; gamma-Glutamyltransferase; Glutathione; Isoxazoles; Kidney; Rats | 1991 |
Inhibition of gamma-glutamyl transpeptidase potentiates the nephrotoxicity of glutathione-conjugated chlorohydroquinones.
Administration of either 2,5-dichloro-3-(glutathion-S-yl)-1, 4-benzoquinone (DC-[GSyl]BQ) or 2,5,6-trichloro-3-(glutathion-S-yl)-1,4-benzoquinone (TC-[GSyl]BQ) to male Sprague-Dawley rats caused dose-dependent (50-200 mumol/kg; iv) renal proximal tubular necrosis, as evidenced by elevations in blood urea nitrogen (BUN), and in the urinary excretion of lactate dehydrogenase (LDH), gamma-glutamyl transpeptidase (gamma-GT) and glucose. Renal proximal tubular necrosis was also confirmed by histological examination of kidney slices prepared from DC-(GSyl)BQ- and TC-(GSyl)BQ-treated animals. Administration of the corresponding hydroquinone conjugates (DC-[GSyl]HQ and TC-[GSyl]HQ), prepared by reducing the quinones with a threefold molar excess of ascorbic acid, resulted in a substantial increase in nephrotoxicity. Moreover, in contrast to other glutathione (GSH)-conjugated hydroquinones, the nephrotoxicity of both DC-(GSyl)HQ and TC-(GSyl)HQ was potentiated when rats were pretreated with AT-125, an irreversible inhibitor of gamma-GT. Neither the quinone-GSH nor the hydroquinone-GSH conjugates caused any effect on liver histology or serum glutamate-pyruvate transaminase levels. The results suggest that coadministration of ascorbic acid with DC-(GSyl)BQ or TC-(GSyl)BQ decreases their interactions with extrarenal nucleophiles, including plasma proteins, and thus increases the concentration of the conjugates delivered to the kidney, and hence toxicity. Furthermore the ability of AT-125 to potentiate the nephrotoxicity of DC-(GSyl)HQ and TC-(GSyl)HQ suggests that metabolism of these conjugates by gamma-GT constitutes a detoxication reaction. Topics: Animals; Ascorbic Acid; Chloranil; Chromatography, High Pressure Liquid; Dose-Response Relationship, Drug; Drug Synergism; Electrochemistry; gamma-Glutamyltransferase; Glutathione; Isoxazoles; Kidney Cortex; Kidney Diseases; Kidney Tubular Necrosis, Acute; Male; Oxidation-Reduction; Rats; Rats, Inbred Strains | 1991 |