Metabolism, not autoxidation, plays a role in alpha-oxoaldehyde- and reducing sugar-induced erythrocyte GSH depletion: relevance for diabetes mellitus.
Erythrocyte and lens reduced glutathione (GSH) levels are often lower in patients with diabetes whereas erythrocyte dicarbonyl levels are often higher. We hypothesise that high plasma carbohydrates may be metabolised by glycolytic and pentose phosphate pathways to form alpha-oxoaldehydes, which deplete cellular GSH. Our aims were: (1) to compare the effectiveness of various carbohydrates or metabolites at depleting erythrocyte GSH, (2) to determine if GSH loss is related to the autoxidation or metabolism of carbohydrates. It was found that erythrocyte GSH was depleted by 50% (ED-50) at t = 2.5 h when erythrocytes were incubated with the following: methylglyoxal (MG) 23 microM, glyoxal 75 microM, DL-glyceraldehyde 299 microM, deoxyribose 606 microM, xylitol 626 microM, and ribose 2 mM. The glycolytic inhibitors, sodium arsenate and KF prevented ribose, deoxyribose, xylitol and MG-induced GSH depletion in erythrocytes over 2 h. However, the antioxidant trolox and the ferric chelator detapac did not affect MG-induced GSH depletion. These data suggest that the carbohydrates or glyceraldehyde were metabolised to form carbonyls such as MG which depleted erythrocyte GSH as a result of catalysis by glyoxalase I. None of the carbohydrates were autoxidised to carbonyls over this time period. We speculate that as a result of GSH depletion, subsequent glycoxidative stress affects erythrocyte function and contributes to diabetic complications.
Department of Pharmaceutical Sciences, University of Toronto, Toronto, ON, Canada.
Kristin M
KM
Beard
Nandita
N
Shangari
Bin
B
Wu
Peter J
PJ
O'Brien
D000447:Aldehydes / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D004912:Erythrocytes / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D005978:Glutathione / Q000097:blood*; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D010084:Oxidation-Reduction
D000447:Aldehydes; D019344:Lactic Acid; D005978:Glutathione; D005947:Glucose