TY - JOUR
T1 - Mitochondrial toxicity of 2-bromohydroquinone in rabbit renal proximal tubules
AU - Schnellmann, Rick G.
AU - Ewell, Fontaine P.Q.
AU - Sgambati, Maria
AU - Mandel, Lazaro J.
N1 - Funding Information:
’ Portions of this work were presented at the Annual Meeting of the American Society for Pharmacology and Experimental Therapeutics, August 18-22, 1985, in Boston, MA. Supported by NIH Grants ES-05329 and AM-286 16 and a grant from the American Heart Association, North Carolina Affiliate. ’ To whom all correspondence should be addressed. 3 Abbreviations used: BHQ, f-bromohydroquinone; FCCP, carbonyl cyanide ptrifluoromethoxy-phenylhydrazone; DMSO, dimethyl sulfoxide; EGTA, ethylene glycol bis(&aminoethyl ether) N, N, N’, N’-tetraacetic acid, GSH, glutathione; HX, hypoxanthine; LDH, lac-
PY - 1987/9/30
Y1 - 1987/9/30
N2 - 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 a 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 a 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 transloca. and/or the F1-ATPase.
AB - 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 a 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 a 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 transloca. and/or the F1-ATPase.
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U2 - 10.1016/0041-008X(87)90134-7
DO - 10.1016/0041-008X(87)90134-7
M3 - Article
C2 - 3660411
AN - SCOPUS:0023205823
SN - 0041-008X
VL - 90
SP - 420
EP - 426
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -