Resistance to Glutathione Depletion in Diabetic and Non-diabetic Human Erythrocytes In-vitro

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Abstract
We have investigated the resistance of erythrocytes from diabetics and non-diabetics to glutathione depletion caused by p-benzoquinone, 1-chloro-2,4-dinitrobenzene (CDNB), diethyl maleate and 4-aminophenol. Incubation of erythrocytes with 4-aminophenol (2mm) caused a precipitous reduction (>80%) in cellular glutathione levels although there was no significant difference between 4-aminophenol-mediated glutathione depletion in the diabetic and non-diabetic cells. p-Benzoquinone and CDNB were both associated with a less severe initial reduction in glutathione levels (>50% at 30 min) although p-benzoquinone caused greater depletion (P < 0.001) at 4.5 h (21.1 ± 3.1%, non-diabetic; 20.0 ± 1.0%, diabetic) compared with CDNB (49.2± 2-2%, non-diabetic; 51.3 ± 1.1% diabetic). Although there was no significant difference between the two types of cell in terms of level of depletion, administration of diethyl maleate caused a significant reduction in glutathione levels at 30 min (P < 0.0005), 3.5h (P < 0.05) and 4.5h (P < 0.05) in erythrocytes from diabetic man compared with those from non-diabetic man. Co-administration of buthionine sulphoximine (20 mm) and 4-aminophenol (l mm) also led to a significant reduction in glutathione levels in diabetic cells at 30 min (P < 0.05), 3.5h (P < 0.02) and 4.5h (P < 0.007) compared with those in non-diabetic cells. The observations that diabetic red cells' resistance to depletion was similar to that of non-diabetic cells for three of the four depletors, and that the combination of 4-aminophenol and buthionine sulphoximine-mediated inhibition of glutathione synthesis was required to illustrate differences suggests that diabetic complications might be a result of the long-term effect of small deficiencies in oxidative self-defence mechanisms such as glutathione.

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