Biomaterial Database

Metabolism and toxicity of 2-bromo-(diglutathion-S-yl)-hydroquinone and 2-bromo-3-(glutathion-S-yl)hydroquinone in the in situ perfused rat kidney. 1994

M I Rivera, and L M Hinojosa, and B A Hill, and S S Lau, and T J Monks

Division of Pharmacology and Toxicology, College of Pharmacy, University of Texas at Austin 78712.

2-Br-(diglutathion-S-yl)hydroquinone (2-Br-(diGSyl)HQ) is a potent nephrotoxicant, causing glucosuria, enzymuria, proteinuria, elevations in blood urea nitrogen, and severe histological alterations to renal proximal tubules at doses of 10-15 mumol/kg. In contrast, 2-Br-3-(glutathion-S-yl)hydroquinone (2-Br-3-(GSyl)HQ) is substantially less nephrotoxic than 2-Br-(diGSyl)HQ and requires a dose of at least 50 mumol/kg to cause modest elevations in blood urea nitrogen concentrations. The reason or reasons for this difference in potency is unclear, but since inhibition of renal gamma-glutamyl transpeptidase (gamma-GT) prevents 2-Br-(diGSyl)HQ-mediated nephrotoxicity, metabolism of these conjugates by the kidney must play an important role. To address this question we have compared the metabolism and toxicity of 2-Br-(diGSyl)HQ and 2-Br-3-(GSyl)HQ in the in situ perfused rat kidney (ISPRK). Following infusion of 20 mumol 2-Br-3-(GSyl)HQ into the right renal artery of male Sprague Dawley rats, a total of 23.5 +/- 1.9% (mean +/- SE) of the dose was accounted for in urine and bile over a period of 180 min. 2-Bromo-3-(cystein-S-yl)hydroquinone and 2-bromo-3-(N-acetylcystein-S-yl)hydroquinone were identified in urine, and unchanged 2-Br-3-(GSyl)HQ was identified in urine and bile. The product arising from the oxidative cyclization of 2-bromo-3-(cystein-S-glycine)hydroquinone, 2H-(3-glycine)-7-hydroxy-8-bromo-1,4-benzothiazine, was also identified in urine.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D007674	Kidney Diseases	Pathological processes of the KIDNEY or its component tissues.	Disease, Kidney,Diseases, Kidney,Kidney Disease
D008297	Male		Males
D008928	Mitochondria	Semiautonomous, self-reproducing organelles that occur in the cytoplasm of all cells of most, but not all, eukaryotes. Each mitochondrion is surrounded by a double limiting membrane. The inner membrane is highly invaginated, and its projections are called cristae. Mitochondria are the sites of the reactions of oxidative phosphorylation, which result in the formation of ATP. They contain distinctive RIBOSOMES, transfer RNAs (RNA, TRANSFER); AMINO ACYL T RNA SYNTHETASES; and elongation and termination factors. Mitochondria depend upon genes within the nucleus of the cells in which they reside for many essential messenger RNAs (RNA, MESSENGER). Mitochondria are believed to have arisen from aerobic bacteria that established a symbiotic relationship with primitive protoeukaryotes. (King & Stansfield, A Dictionary of Genetics, 4th ed)	Mitochondrial Contraction,Mitochondrion,Contraction, Mitochondrial,Contractions, Mitochondrial,Mitochondrial Contractions
D010101	Oxygen Consumption	The rate at which oxygen is used by a tissue; microliters of oxygen STPD used per milligram of tissue per hour; the rate at which oxygen enters the blood from alveolar gas, equal in the steady state to the consumption of oxygen by tissue metabolism throughout the body. (Stedman, 25th ed, p346)	Consumption, Oxygen,Consumptions, Oxygen,Oxygen Consumptions
D010477	Perfusion	Treatment process involving the injection of fluid into an organ or tissue.	Perfusions
D005978	Glutathione	A tripeptide with many roles in cells. It conjugates to drugs to make them more soluble for excretion, is a cofactor for some enzymes, is involved in protein disulfide bond rearrangement and reduces peroxides.	Reduced Glutathione,gamma-L-Glu-L-Cys-Gly,gamma-L-Glutamyl-L-Cysteinylglycine,Glutathione, Reduced,gamma L Glu L Cys Gly,gamma L Glutamyl L Cysteinylglycine
D006873	Hydroquinones	Derivatives of hydroquinone (1,4-dihydrobenzene) made by reduction of BENZOQUINONES.	Quinol,p-Dihydroxybenzenes,para-Dihydroxybenzenes,Quinols,p Dihydroxybenzenes,para Dihydroxybenzenes
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D017207	Rats, Sprague-Dawley	A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.	Holtzman Rat,Rats, Holtzman,Sprague-Dawley Rat,Rats, Sprague Dawley,Holtzman Rats,Rat, Holtzman,Rat, Sprague-Dawley,Sprague Dawley Rat,Sprague Dawley Rats,Sprague-Dawley Rats