Abstract
The respective methaemoglobin forming and GSH depleting capabilities of monoacetyl dapsone hydroxylamine (MADDS–NHOH) and dapsone hydroxylamine (DDS–NHOH) were compared in human diabetic and non-diabetic erythrocytes in vitro with a view to select the most potent agent for future oxidative stress and antioxidant evaluation studies. Administration of both metabolites to non-diabetic erythrocytes over the 20 min period of the study resulted in significantly more methaemoglobin formation at all four time points compared with the diabetic erythrocytes ( P<0.0001). At all four time points, significantly more methaemoglobin was formed in response to MADDS–NHOH in non-diabetic cells compared with the effects of DDS–NHOH on diabetic erythrocytes ( P<0.0001). At the 5 and 10 min time points, significantly more methaemglobin was formed in non-diabetic cells in the presence of MADDS–NHOH compared with DDS–NHOH ( P<0.05). At the 5 min time point only, significantly more methaemoglobin was formed in the presence of MADDS–NHOH in diabetic cells compared with that of DDS–NHOH ( P<0.01). However, compared with diabetic control GSH levels, the presence of DDS–NHOH caused a significant depletion in GSH at 5, 10 and 20 min time points in diabetic cells ( P<0.001). In addition, the presence of DDS–NHOH caused a significant reduction in GSH levels in diabetic cells in comparison with those of non-diabetics at the 5, 10 and 20 min, ( P<0.005). DDS–NHOH was also associated with a significant depletion of GSH levels in diabetic cells compared with those of non-diabetic control erythrocytes ( P<0.0001). The presence of MADDS–NHOH in diabetic erythrocytes led to a significant reduction in GSH levels at the 20 min time point compared with those of non-diabetics ( P<0.001), but there were no significant differences at the 5, 10 and 15 min points. Due to its greater GSH-depleting action, DDS–NHOH will be selected for future use in the oxidative stress assessment in diabetic erythrocytes.
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