Taurine Counteracts Oxidative Stress and Nerve Growth Factor Deficit in Early Experimental Diabetic Neuropathy

• Published in: Experimental neurology 2001-11, Vol.172 (1), p.211-219
• Main Authors: Obrosova, Irina G., Fathallah, Lamia, Stevens, Martin J.
• Format: Article
• Language: English
• Subjects: 4-hydroxyalkenals; Aldehydes - metabolism; Animals; ascorbate; Ascorbic Acid - metabolism; Associated diseases and complications; Biological and medical sciences; Blood Glucose - drug effects; Body Weight - drug effects; Diabetes Mellitus, Experimental - chemically induced; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - etiology; Diabetic Neuropathies - physiopathology; Dietary Supplements; Disease Models, Animal; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; glutathione; Glutathione - metabolism; Lipid Peroxidation - drug effects; Male; malondialdehyde; Malondialdehyde - metabolism; Medical sciences; nerve growth factor; Nerve Growth Factor - deficiency; Nerve Growth Factor - metabolism; oxidative stress; Oxidative Stress - drug effects; rat; Rats; Rats, Wistar; sciatic nerve; Sciatic Nerve - drug effects; Sciatic Nerve - metabolism; Streptozocin; streptozotocin-induced diabetes; taurine; Taurine - administration & dosage; Taurine - metabolism
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1006/exnr.2001.7789

Oxidative stress has a key role in the pathogenesis of diabetic complications. We have previously reported that taurine (T), which is known to counteract oxidative stress in tissues (lens, kidney, retina) of diabetic rats, attenuates nerve blood flow and conduction deficits in early experimental diabetic neuropathy (EDN). The purpose of this study was to evaluate whether dietary 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 the sciatic nerve. Malondialdehyde (MDA) plus 4-hydroxyalkenals (4-HA) were quantified with N-methyl-2-phenylindole. GSH, GSSG, dehydroascorbate (DHAA), and ascorbate (AA) were assayed spectrofluorometrically, T by reverse-phase HPLC, and NGF by ELISA. MDA plus 4-HA concentration (mean ± SEM) was increased in diabetic rats (0.127 ± 0.006 vs 0.053 ± 0.003 μmol/g in controls, P < 0.01), and this increase was partially prevented by T (0.096 ± 0.004, P < 0.01 vs untreated diabetic group). GSH levels were similarly decreased in diabetic rats treated with or without taurine vs controls. GSSG levels were similar in control and diabetic rats but were lower in diabetic rats treated with T (P < 0.05 vs controls). AA levels were decreased in diabetic rats (0.133 ± 0.015 vs 0.219 ± 0.023 μmol/g in controls, P < 0.05), and 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 μmol/g in controls, P < 0.05) and were repleted by T supplementation (4.2 ± 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 ± 0.28, P < 0.05 vs diabetic group). In conclusion, T counteracts oxidative stress and the NGF deficit in early EDN. Antioxidant effects of T in peripheral nerve are, at least in part, mediated through the ascorbate system of antioxidative defense. The findings are consistent with the important role for oxidative stress in impaired neurotrophic support in EDN.