REDUCTION OF DAPSONE HYDROXYLAMINE TO DAPSONE DURING METHEMOGLOBIN FORMATION IN HUMAN ERYTHROCYTES IN-VITRO .3. EFFECT OF DIABETES

The fate of dapsone hydroxylamine has been investigated in diabetic an d normal human erythrocytes. In erythrocytes from four type 1 (insulin dependent) diabetic subjects, there was a significant decrease in dap sone hydroxylamine-mediated methaemoglobin formation compared with cel ls drawn from normal individuals (P < 0.01). However, the ability of t he diabetic cells to detoxify the hydroxylamine to dapsone was not cor respondingly reduced and was not different to normal cells. The initia l;ate of the accelerating effect of diethyl dithiocarbamate (DDC) on h ydroxplamine-mediated methaemoglobin and dapsone formation was signifi cantly reduced in diabetic compared with normal cells. There was no si gnificant difference in hydroxylamine-dependent methaemoglobin formati on between diabetic erythrocytes pretreated with either statil or sorb inil and untreated diabetic cells. Dapsone recovery in diabetic erythr ocytes incubated with statil was not significantly different from stat il-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 si gnificantly 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 hydroxylamin e-mediated methaemoglobin formation in comparison with normal cells, g lutathione-dependent hydroxylamine reduction to dapsone was unaffected .