Early Antioxidant Supplementation in the Prevention of Diabetic Nephropathy: Alterations in NOS Expression Precede Renal Functional Decline

Rat and human studies have shown that good glycemic control alone is not sufficient to prevent the complications associated with diabetes, such as nephropathy. A proposed culprit is excessive oxidative stress in the cells and vasculature of the kidney resulting in endothelial cell dysfunction, which is one of the earliest and most pivotal consequences seen in early diabetes. We hypothesized that an antioxidant (AO) diet would alleviate the oxidative stress and prevent and/or delay the progression of diabetic nephropathy, even with poor glycemic control. Early nephropathy in diabetes is associated with increased intra renal nitric oxide (NO) production. Nitric oxide synthases (NOS) are a family of enzymes that catalyze the production of NO. We report significantly lower endothelial nitric oxide synthase (eNOS) with AO supplementation compared to the other 2 groups, which means the AO diet led to the decrease in eNOS in the early phase of the onset of diabetic nephropathy. Also, we noted a significant decrease in neuronal nitric oxide synthase (nNOS) with AO supplementation, which is consistent with renal protection in the later phase of diabetic nephropathy. Our results reveal evidence of molecular damage to the endothelium and specialized structures of the kidney that precedes the onset of diabetes. These results suggest early AO supplementation safeguards the kidneys from some of the forces that induce hyperfiltration in early-stage diabetic nephropathy.