Relationship Between Aldose Reductase And Oxidative Stress In Diabetic Peripheral Nerve

Abstract

The relationship between aldose reductase (AR) activity and oxidative stress in tissue sites for diabetic complications remains controversial. We evaluated the ARI sorbinil and three antioxidants, i.e. DL‐α‐lipoic acid (LA), taurine (T) and vitamin E (VE), on indices of oxidative stress and sorbitol pathway intermediates in diabetic peripheral nerve. The groups included control (C) and streptozotocin‐diabetic (D) rats treated with/without: 1.ARI (65 mg/kg, for 2 wks after 4 wks of untreated diabetes); 2.T (1% of the diet); 3.VE (1% of the diet); or 4.LA(100 mg/kg i.p.). T, VE and LA were administered for 6 wks from induction of diabetes. Malondialdehyde plus 4‐hydroxyalkenal levels were increased in D vs C (p < 0.01) and this increase was corrected in D+ARI (p < 0.01 vs D). GSH and ascorbate levels as well as superoxide dismutase activity were decreased in D vs C, and this decrease was completely (GSH) or partially corrected by ARI. Three antioxidants counteracted oxidative stress, but not accumulation of the sorbitol pathway intermediates in the diabetic nerve. In conclusion, increased AR activity contributes to rather than protects from oxidative stress in the diabetic nerve. Oxidative stress is not a cause of sorbitol pathway intermediate accumulation in experimental diabetic neuropathy.