TY - JOUR
T1 - Differential uptake of isomeric 2-bromohydroquinone-glutathione conjugates into kidney slices
AU - Lau, Serrine S.
AU - McMenamin, Mary G.
AU - Monks, Terrence J.
N1 - Funding Information:
ACKNOWLEDGEMENTS: This research was supported in part by USPHS Grants ES 04662 awarded by the National Institute of Environmental Health Sciences and GM 39338 awarded by the National Institutes of Health.
PY - 1988/4/15
Y1 - 1988/4/15
N2 - 2-Bromo-(diglutathion-Syl)hydroquinone (2-Br-[diGSyl]HQ) is a more potent nephrotoxicant than any of three mono-substituted isomers. The reason for this differential toxicity is unknown. We now report that the rate of uptake of 2-Br-(diGSyl)HQ, 2-Br-3-(GSyl)HQ, 2-Br-5-(GSyl)-HQ and 2-Br-6(GSyl)HQ by kidney slices was 2.4, 1.2, 1.0 and 0.3 nmoles/mg/10 min, respectively. AT-125 (0.5 mM) inhibited γ-glutamyl transpeptidase (GGT) in intact and homogenized kidney slices by 47% and 92%, respectively and decreased the accumulation of the isomeric [35S]-conjugates by 49%, 21%, 25% and 30%, respectively. The data suggest that the accumulation of 2-Br-(GSyl)HQ conjugates into isolated kidney slices may in part be mediated by GGT and that the more extensive renal uptake of the di-substituted conjugate may be partially responsible for its enhanced nephrotoxicity. In addition, 2-Br-(diGSyl)HQ gave rise to the most covalently bound material of the different isomers studied suggesting that both physiological and biochemical factors contribute to the potent and selective nephrotoxicity of this compound.
AB - 2-Bromo-(diglutathion-Syl)hydroquinone (2-Br-[diGSyl]HQ) is a more potent nephrotoxicant than any of three mono-substituted isomers. The reason for this differential toxicity is unknown. We now report that the rate of uptake of 2-Br-(diGSyl)HQ, 2-Br-3-(GSyl)HQ, 2-Br-5-(GSyl)-HQ and 2-Br-6(GSyl)HQ by kidney slices was 2.4, 1.2, 1.0 and 0.3 nmoles/mg/10 min, respectively. AT-125 (0.5 mM) inhibited γ-glutamyl transpeptidase (GGT) in intact and homogenized kidney slices by 47% and 92%, respectively and decreased the accumulation of the isomeric [35S]-conjugates by 49%, 21%, 25% and 30%, respectively. The data suggest that the accumulation of 2-Br-(GSyl)HQ conjugates into isolated kidney slices may in part be mediated by GGT and that the more extensive renal uptake of the di-substituted conjugate may be partially responsible for its enhanced nephrotoxicity. In addition, 2-Br-(diGSyl)HQ gave rise to the most covalently bound material of the different isomers studied suggesting that both physiological and biochemical factors contribute to the potent and selective nephrotoxicity of this compound.
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U2 - 10.1016/S0006-291X(88)80703-4
DO - 10.1016/S0006-291X(88)80703-4
M3 - Article
C2 - 2895999
AN - SCOPUS:0023912849
SN - 0006-291X
VL - 152
SP - 223
EP - 230
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 1
ER -