OBJECTIVE: To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy. RESEARCH DESIGN AND METHODS: We used the model of streptozotocin-induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes. RESULTS: NBF in SDN was reduced by 50%; LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was improved in a dose-dependent manner in LA-supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA. CONCLUSIONS: These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of human diabetic neuropathy.
OBJECTIVE: To determine whether lipoic acid (LA) will reduce oxidative stress in diabetic peripheral nerves and improve neuropathy. RESEARCH DESIGN AND METHODS: We used the model of streptozotocin-induced diabetic neuropathy (SDN) and evaluated the efficacy of LA supplementation in improving nerve blood flow (NBF), electrophysiology, and indexes of oxidative stress in peripheral nerves affected by SDN, at 1 month after onset of diabetes and in age-matched control rats. LA, in doses of 20, 50, and 100 mg/kg, was administered intraperitoneally five times per week after onset of diabetes. RESULTS: NBF in SDN was reduced by 50%; LA did not affect the NBF of normal nerves but improved that of SDN in a dose-dependent manner. After 1 month of treatment, LA-supplemented rats (100 mg/kg) exhibited normal NBF. The most sensitive and reliable indicator of oxidative stress was reduction in reduced glutathione, which was significantly reduced in streptozotocin-induced diabetic and alpha-tocopherol-deficient nerves; it was improved in a dose-dependent manner in LA-supplemented rats. The conduction velocity of the digital nerve was reduced in SDN and was significantly improved by LA. CONCLUSIONS: These studies suggest that LA improves SDN, in significant part by reducing the effects of oxidative stress. The drug may have potential in the treatment of humandiabetic neuropathy.
Authors: Roman Stavniichuk; Viktor R Drel; Hanna Shevalye; Yury Maksimchyk; Tamara M Kuchmerovska; Jerry L Nadler; Irina G Obrosova Journal: Exp Neurol Date: 2011-04-16 Impact factor: 5.330
Authors: Irina G Obrosova; Roman Stavniichuk; Viktor R Drel; Hanna Shevalye; Igor Vareniuk; Jerry L Nadler; Robert E Schmidt Journal: Am J Pathol Date: 2010-08-19 Impact factor: 4.307
Authors: Roman Stavniichuk; Hanna Shevalye; Hiroko Hirooka; Jerry L Nadler; Irina G Obrosova Journal: Biochem Pharmacol Date: 2012-01-20 Impact factor: 5.858
Authors: Viktor R Drel; Pal Pacher; Igor Vareniuk; Ivan A Pavlov; Olga Ilnytska; Valeriy V Lyzogubov; Seth R Bell; John T Groves; Irina G Obrosova Journal: Int J Mol Med Date: 2007-12 Impact factor: 4.101