2-Bromohydroquinone-induced toxicity to rabbit renal proximal tubules: evidence against oxidative stress.
2-Bromohydroquinone (BHQ) plays an important role in bromobenzene-induced nephrotoxicity and is a model toxic hydroquinone. Since BHQ has a quinone nucleus and various quinones have been shown to produce cytotoxicity via oxidative stress, the goal of this study was to determine whether BHQ produced cytotoxicity in a suspension of rabbit renal proximal tubules via oxidative stress. t-Butyl hydroperoxide (TBHP), an agent known to produce cytotoxicity via oxidative stress in this preparation, was used as a positive control. BHQ decreased tubular glutathione disulfide content whether glutathione reductase was inhibited or not. Inhibition of glutathione reductase did not result in the potentiation of BHQ-induced mitochondrial dysfunction or cell death. In contrast, TBHP increased tubular glutathione disulfide content. TBHP-induced increases in glutathione disulfide content, mitochondrial dysfunction, and cell death were potentiated when glutathione reductase was inhibited. Unlike TBHP, BHQ did not initiate lipid peroxidation nor was the antioxidant butylated hydroxytoluene protective. However, BHQ and TBHP both increased sodium cyanide-insensitive oxygen consumption. These results suggest that BHQ may undergo "redox cycling," but BHQ-induced mitochondrial dysfunction and cell death are not due to oxidative stress.
Schnellmann
R G
RG
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology; D002084:Butylated Hydroxytoluene / Q000633:toxicity; D002330:Carmustine / Q000633:toxicity; D002470:Cell Survival; D005978:Glutathione / Q000031:analogs & derivatives / Q000032:analysis; D019803:Glutathione Disulfide; D005980:Glutathione Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006873:Hydroquinones / Q000378:metabolism / Q000633:toxicity*; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects; D010545:Peroxides / Q000633:toxicity; D011817:Rabbits; D020122:tert-Butylhydroperoxide
D006873:Hydroquinones; D010545:Peroxides; D002084:Butylated Hydroxytoluene; C042377:2-bromohydroquinone; D020122:tert-Butylhydroperoxide; D005980:Glutathione Reductase; D005978:Glutathione; D001205:Ascorbic Acid; D002330:Carmustine; D019803:Glutathione Disulfide