Use of in vitro methaemoglobin generation to study antioxidant status in the diabetic erythrocyte

Poor glycaemic control in diabetes and a combination of oxidative, metaboli c, and carbonyl stresses are thought to lead to widespread non-enzymatic gl ycation and eventually to diabetic complications. Diabetic tissues can suff er both restriction in their supply of reducing power and excessive demand for reducing power. This contributes to compromised antioxidant status, par ticularly in the essential glutathione maintenance system. To study and ult imately correct deficiencies in diabetic glutathione maintenance, an experi mental model would be desirable, which would provide in vitro a rapid, conv enient, and dynamic reflection of the performance of diabetic GSH antioxida nt capacity compared with that of non-diabetics. Xenobiotic-mediated in viv o methaemoglobin formation in erythrocytes drawn from diabetic volunteers i s significantly lower than that in erythrocytes of non diabetics. Aromatic hydroxylamine-mediated methaemoglobin formation is GSH-dependent and is ind icative of the ability of an erythrocyte to maintain GSH levels during rapi d thiol consumption. Although nitrite forms methaemoglobin through a comple x GSH-independent pathway, it also reveals deficiencies in diabetic detoxif ication and antioxidant performance compared with non diabetics. Together w ith efficient glycaemic monitoring, future therapy of diabetes may include trials of different antiglycation agents and antioxidant combinations. Equa lization in vitro of diabetic methaemoglobin generation with that of age/se x-matched non diabetic subjects might provide an early indication of diabet ic antioxidant status improvement in these studies. (C) 2000 Elsevier Scien ce Inc.