Reduction of dapsone hydroxylamine to dapsone during methaemoglobin formation in human erythrocytes in vitro. III: Effect of diabetes.
The fate of dapsone hydroxylamine has been investigated in diabetic and normal human erythrocytes. In erythrocytes from four type 1 (insulin dependent) diabetic subjects, there was a significant decrease in dapsone hydroxylamine-mediated methaemoglobin formation compared with cells drawn from normal individuals (P < 0.01). However, the ability of the diabetic cells to detoxify the hydroxylamine to dapsone was not correspondingly reduced and was not different to normal cells. The initial rate of the accelerating effect of diethyl dithiocarbamate (DDC) on hydroxylamine-mediated methaemoglobin and dapsone formation was significantly reduced in diabetic compared with normal cells. There was no significant difference in hydroxylamine-dependent methaemoglobin formation between diabetic erythrocytes pretreated with either statil or sorbinil and untreated diabetic cells. Dapsone recovery in diabetic erythrocytes incubated with statil was not significantly different from statil-free incubations. However, in the presence of sorbinil, there was a marked reduction in dapsone formation at all four time points, (P < 0.001 at 15 min). Mean measured levels of glutathione did not differ significantly between the normal (380 +/- 30.9 mg/L; N = 8) and diabetic (349 +/- 58.7 mg/L; N = 8) volunteers. In summary, although diabetic erythrocytes were less sensitive to the effect of dapsone hydroxylamine-mediated methaemoglobin formation in comparison with normal cells, glutathione-dependent hydroxylamine reduction to dapsone was unaffected.
Coleman
M D
MD
Department of Pharmaceutical Sciences, Aston University, Birmingham, U.K.
Simpson
J
J
Jacobus
D P
DP
D003622:Dapsone / Q000031:analogs & derivatives* / Q000494:pharmacology; D003920:Diabetes Mellitus / Q000378:metabolism*; D004050:Ditiocarb / Q000494:pharmacology; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D008706:Methemoglobin / Q000096:biosynthesis*; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010793:Phthalazines / Q000494:pharmacology; D013696:Temperature
D007093:Imidazoles; D048289:Imidazolidines; D010793:Phthalazines; C042829:ponalrestat; D003622:Dapsone; D008706:Methemoglobin; D004050:Ditiocarb; C026411:sorbinil; D005978:Glutathione; C018209:4-amino-4'-hydroxylaminodiphenylsulfone