Abstract

BACKGROUND
Diabetes mellitus is postulated to be associated with increased lipid peroxidation which may contribute to vascular complications. One potential mechanism of the increased lipid peroxidation in diabetes is lipid-linked advanced glycosylation and oxidation. Aminoguanidine(AMGN), the prototype inhibitor of advanced glycosylation end-product formation, has been recently shown to prevent oxidative moditication of LDL in vitro at moderate concentration. It is unknown whether AMGN might act as an anti-oxidant against lipid peroxidation under hyperglycemia in vivo. METHODS: To investigate the in vivo effect of AMGN on lipid peroxidation in diabetes, we administered AMGN(1 g/L in drinking water) or vitamin E (400mg/day, 5 days/week) to streptozotocin(STZ)-induced diabetic rats for 9 weeks and measured plasma lipid hydroperoxides by ferrous oxidation with xylenol orange II method and RBC membrane malon-dialdehyde(MDA) by thiobarbituric acid method. RESULTS: Plasma lipid hydroperoxide level was higher in STZ-induced diabetic rats than in control rats(7.53+/-2.03 vs.5.62+/-0.44*pmol/L). RBC membrane MDA was also higher in STZ-induced diabetic rats than in control rats(2.67+/-0.46 vs. 1.81+/-0.19* nmol/mL). Plasma lipid hydroperoxide level was lower in AMGN-treated(6.23+/-0.59*umol/L) and vitamin E-treated(5.29+/-0.27*umol/L) diabetic rats than in untreated diabetic rats. RBC membrane MDA was also lower in AMGN-treated(1.93+/-0.12""'nmol/ mL) diabetic rats than in untreated diabetic rats. There was no significant difference in plasma glucose, triglyceride levels among diabetic groups(Mean +/-S.D; *, P<0.05 vs. untreated STZ-induced diabetic rats; n=8-14/group). CONCLUSION: Although the mechanisms of action of AMGN on lipid peroxidation in vivo should be studied further, these results suggest that AMGN might have an additional beneficial effect as an antioxidant against lipid peroxidation in prevention trial for diabetic vascular complications.

• Keywords: Lipid peroxidation;Aminoguanidine;STZ-diabetic rats;