Transferrin Modifications and Lipid Peroxidation: Implications in Diabetes Mellitus

Abstract

Free iron is capable of stimulating the production of free radicals which cause oxidative damage such as lipid peroxidation. One of the most important mechanisms of antioxidant defense is thus the sequestration of iron in a redox-inactive form by transferrin. In diabetes mellitus, increased oxidative stress and lipid peroxidation contribute to chronic complications but it is not known if this is related to abnormalities in transferrin function. In this study we investigated the role of transferrin concentration and glycation. The antioxidant capacity of apotransferrin to inhibit lipid peroxidation by iron-binding decreased in a concentration-dependent manner from 89% at <formula>≥2 mg/ml</formula> to 42% at 0.5 mg/ml. Pre-incubation of apotransferrin with glucose for 14 days resulted in a concentration-dependent increase of glycation: 1, 5 and 13 μmol fructosamine/g transferrin at 0, 5.6 and 33.3 mmol/l glucose respectively, p<0.001. This was accompanied by a decrease in the iron-binding antioxidant capacity of apotransferrin. In contrast, transferrin glycation by up to 33.3 mmol/l glucose did not affect chemiluminescence-quenching antioxidant capacity, which is iron-independent. Colorimetric evaluation of total iron binding capacity in the presence of an excess of iron (iron/transferrin molar ratio=2.4) also decreased from 0.726 to 0.696 and 0.585 mg/g transferrin after 0, 5.6 and 33.3 mmol/l glucose, respectively, p<0.01. In conclusion, these results suggest that lower transferrin concentration and its glycation can, by enhancing the pro-oxidant effects of iron, contribute to the increased lipid peroxidation observed in diabetes.

• Diabetes
• Lipid Peroxidation
• Iron
• Transferrin
• Glycation
• Fl-aTf, Fluorescein-labelled Apotransferrin
• Abap, 2,2-azo-bis(2-amidinopropane) Hydrochloride
• Age, Advanced Glycated Endproduct
• Au, Absorption Units
• Fas, Ferrous Ammonium Sulphate
• Ib, Iron-binding
• Mda, Malondialdehyde
• Nta, Nitrilotriacetate
• Tac-PI, Total Antioxidant Capacity--percent Inhibition Of The Chemiluminescence
• Tba, Thiobarbituric Acid
• Tbars, Thiobarbituric Acid Reactive Substances
• Tibc, Total Iron-binding Capacity
• Uibc, Unsaturated Iron-binding Capacity