Taurine counteracts oxidative stress and nerve growth factor deficit in early experimental diabetic neuropathy

Oxidative stress has a key role in the pathogenesis of diabetic complicatio ns. We have previously reported that taurine (T), which is known to counter act oxidative stress in tissues (lens, kidney, retina) of diabetic rats, at tenuates nerve blood flow and conduction deficits in early experimental dia betic neuropathy (EDN). The purpose of this study was to evaluate whether d ietary T supplementation counteracts oxidative stress and the nerve growth factor (NGF) deficit in the diabetic peripheral nerve. The experiments were performed in control rats and streptozotocin-diabetic rats fed standard or 1% T-supplemented diets for 6 weeks. All measurements were performed in th e sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were q uantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phas e HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean +/- SEM) was in creased in diabetic rats (0.127 +/-0.006 vs 0.053 +/-0.003 mu mol/g in cont rols, P<0.01), and this increase was partially prevented by T (0.096<plus/m inus>0.004, P<0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSS G levels were similar in control and diabetic rats but were lower in diabet ic rats treated with T (P<0.05 vs controls). AA levels were decreased in di abetic rats (0.133+0.015 vs 0.219 +/-0.023 mu mol/g in controls, P<0.05), a nd this deficit was prevented by T. DHAA/AA ratio was increased in diabetic rats vs controls (P<0.05), and this increase was prevented by T. T levels were decreased in diabetic rats (2.7 +/-0.16 vs 3.8 +/-0.1 mu mol/g in cont rols, P<0.05) and were repleted by T supplementation (4.2<plus/minus>0.3). NGF levels were decreased in diabetic rats (2.35 +/-0.20 vs 3.57 +/-0.20 ng /g in controls, P<0.01), and this decrease was attenuated by T treatment (3 .16<plus/minus>0.28, P<0.05 vs diabetic group). In conclusion, T counteract s oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbat e system of antioxidative defense. The findings are consistent with the imp ortant role for oxidative stress in impaired neurotrophic support in EDN. ( C) 2001 Academic Press.