Reversal of hyperglycemia and diabetic nephropathy: effect of reinstitution of good metabolic control on oxidative stress in the kidney of diabetic rats.

Studies have shown that good metabolic control (GC) is beneficial in slowing the progression of nephropathy in diabetes, and if the duration of poor metabolic control (PC) is prolonged before reinstitution of GC, nephropathy is not easily reversed. This study is to identify the biochemical abnormalities that could contribute to the resistance of nephropathy to reverse after establishment of GC in rats. The effect of reinstitution of GC and its duration is evaluated on oxidative stress and nitric oxide (NO) levels in the renal cortex and urine of diabetic rats. The rats were maintained in GC (5% glycated hemoglobin, GHb) soon after or 6 months after induction of hyperglycemia, and were sacrificed 13 months after induction of diabetes. For rats in which GC was initiated soon after induction of diabetes, oxidative stress [as measured by the levels of lipid peroxides (LPOs), 8-hydroxy-2'-deoxyguanosine (8-OHdG), and reduced glutathione (GSH)] and NO in urine and renal cortex were not different from that observed in normal control rats, but when reinstitution of GC was delayed for 6 months after induction of diabetes, oxidative stress and NO remain elevated in both urine and renal cortex. This suggests that hyperglycemia-induced oxidative stress and NO can be prevented if GC is initiated very early, but are not easily reversed if PC is maintained for longer durations. Understanding the mechanisms responsible for this phenomenon could reveal novel means to reverse nephropathy in diabetic patients.