Inhibition of DNA glycoxidation by mannitol and Pyridoxamine: Implications for DNA-antibody development in diabetes and diabetic retinopathy.

Chronic exposure to reactive carbonyl species such as glyoxal and methylglyoxal, along with hydroxyl radicals (•OH), leads to glycative and oxidative damage, contributing to insulin resistance and diabetic complications. Pyridoxamine (PM) is known to counteract these effects, but its potential synergy with mannitol (MN), a hydroxyl radical scavenger, remains unexplored. This study investigates the combined efficacy of MN and PM in preventing glycation and oxidative damage in vitro. Calf thymus DNA was subjected to glycation using 10 mM glyoxal, oxidation via the Fenton reaction, and sequential glycoxidation (glycation followed by oxidation). The inhibitory effects of MN, PM, and their combination were assessed using NBT reduction for early glycation, GK-ribose for AGEs, TBARS for hydroxyl radicals, and spectroscopic analyses for AGEs formation. A clinical study also examined autoantibody prevalence in diabetes and diabetic retinopathy (DR). Results showed that glycoxidated DNA exhibited structural alterations, with MN and PM individually reducing ketoamine content. Their combination further enhanced glycation and glycoxidation inhibition. Additionally, MN-PM co-administration synergistically reduced AGEs and hydroxyl radicals. Autoantibody levels were elevated in diabetes and DR. These findings suggest PM-MN co-administration as a promising strategy to mitigate diabetic complications.