Effects of oxidised alpha-lipoic acid and alpha-tocopherol on xenobiotic-mediated methaemoglobin formation in diabetic and non-diabetic human erythrocytes in-vitro

The effects of oxidised alpha-lipoic acid and alpha-tocopherol were investi gated on a human erythrocytic in vitro model of diabetic metabolic stress. Preincubation of non-diabetic and diabetic erythrocytes with oxidised alpha -lipoic acid or alpha-tocopherol resulted in marked increases in nitrite-me diated methaemoglobin formation. In contrast, oxidised alpha-lipoic acid re sulted in considerable reductions in 4-aminophenol-mediated methaemoglobin formation in both diabetic and non-diabetic cells. alpha-Tocopherol showed an increase only in diabetic cells, at one time point. Monoacetyl dapsone h ydroxylamine (MADDS - NHOH)-mediated methaemoglobin formation was reduced b y oxidised zeta-lipoic acid in non-diabetic and diabetic cells at all three time points, although alpha-tocopherol had no effect with MADDS-NHOH. In d iabetic cells only, alpha-tocopherol incubation caused a reduction in GSH l evels compared with non-diabetic cells. As the agents showed pro- as well a s anti-oxidant effects in this study, further studies are required to demon strate potential diabetic benefit from alpha-lipoic acid adminstration. (C) 2000 Published by Elsevier Science B.V. All rights reserved.