This report provides a new possible link between increased lipid peroxidation and tissue damage in diabetes. Advanced Glycation End products (AGEs) have been well established as one of the major factors responsible for multiorgan damage seen in diabetes and aging. We report here that the interaction between lipid peroxidation products and the long-lived structural protein, collagen, results in the formation of products that are structurally or immunologically similar to AGEs. Enzyme-linked immunoassays revealed crossreactivity between anti-AGE antibodies and collagen incubated with linoleic acid/arachidonic acid for 4 weeks under oxidative conditions. Formation of AGEs from lipid oxidation products and collagen was further confirmed by the inhibitory effect of aminoguanidine. Similarly, incubation of collagen with an end product of lipid peroxidation, malondialdehyde (MDA), resulted in the formation of AGEs. It was also noted that the incubation of collagen with equimolar concentrations of glucose or linoleic acid/arachidonic acid resulted in the formation of almost similar amount of AGEs. Another interesting observation was that the level of AGEs correlated well with the crosslinking of collagen (r=0.93) and also with the intensity of fluorescence (ex: 390 nm/em: 460 nm) (r=0.99). However the rate of fluorescence development was observed at a faster rate than the formation of AGEs when the concentration of MDA was increased from 5 mM to 25/50 mM. Free radical scavengers failed to prevent lipid peroxidation-induced formation of AGEs. These results suggest that, in addition to reducing sugars, fatty acid oxidation products can also lead to the formation of products that are structurally similar to AGEs. The work presents a possible link between lipid peroxidation and diabetic complications, through AGEs. This study also suggests that the formation of AGEs is a possible explanation for lipid peroxide-induced crosslinking of collagen.
Volume 135, 2023
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