Mitochondrial toxicity of 2-bromohydroquinone in rabbit renal proximal tubules.
2-Bromohydroquinone (BHQ) is a nephrotoxic metabolite of bromobenzene and a model toxic hydroquinone. The primary goal of these studies was to determine whether BHQ produces toxicity in rabbit renal proximal tubules by inhibiting mitochondrial function. BHQ induces a specific sequence of cellular events. Initially there was decrease in tubular glutathione content followed by a decrease in nystatin-stimulated ouabain-sensitive respiration. A decrease in cell viability, as measured by a decrease in lactate dehydrogenase retention, was late event. Associated with the decrease in respiration was a decrease in intracellular ATP content. Probing of mitochondrial function in the tubule revealed that BHQ did inhibit mitochondrial function in a somewhat selective manner. State 3 respiration was inhibited prior to changes in the rate of electron flow through cytochrome c-cytochrome oxidase. It is postulated that BHQ may initially inhibit state 3 respiration by inhibiting the adenine nucleotide translocator and/or the F1-ATPase.
Schnellmann
R G
RG
Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia, Athens 30602.
Ewell
F P
FP
Sgambati
M
M
Mandel
L J
LJ
D000249:Adenosine Monophosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D005978:Glutathione / Q000032:analysis; D006873:Hydroquinones / Q000633:toxicity*; D019271:Hypoxanthine; D007042:Hypoxanthines / Q000032:analysis; D066298:In Vitro Techniques; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D011817:Rabbits
D006873:Hydroquinones; D007042:Hypoxanthines; D019271:Hypoxanthine; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D000249:Adenosine Monophosphate; C042377:2-bromohydroquinone; D000255:Adenosine Triphosphate; D005978:Glutathione