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Hypoxia Is Not A Cause Of Oxidative Stress In Diabetic Peripheral Nerve
Author(s) -
Obrosova Ig,
Van Huysen C,
Fathallah L,
Stevens Mj
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000abstracts-32.x
Subject(s) - endocrinology , oxidative stress , medicine , hypoxia (environmental) , lipid peroxidation , diabetes mellitus , chemistry , prazosin , glutathione , nad+ kinase , ischemia , pharmacology , antagonist , biochemistry , oxygen , enzyme , receptor , organic chemistry
Severe ischemia and hypoxia in the neural tissues are associated with free radical production. The purpose of our study was to explore the contribution of endoneurial hypoxia vs hyperglycemia to oxidative stress in early experimental diabetic neuropathy. This was achieved by evaluating α 1 ‐adrenoceptor antagonist prazosin (5 mg/kg in the drinking water, for 3 wks from induction of diabetes), on diabetes‐induced changes in endoneurial vascular conductance (VC), biochemical markers of nerve hypoxia, lipid peroxidation and antioxidative defense. Diabetes‐induced decrease in VC as well as free NAD + /NADH ratios in mitochondrial cristae, matrix and cytosol, were completely (VC, free NAD + /NADH in mitochondrial matrix) or partially prevented by prazosin. Accumulation of lipid peroxidation products, depletion of GSH, ascorbate and taurine, increase in GSSG/GSH and DHAA/AA ratios were not affected by vasodilator therapy. Antioxidative defense enzyme activities were similar in control and diabetic rats treated with/without prazosin. Blood and nerve glucose concentrations were similarly elevated in prazosin‐treated and untreated diabetic rats. In conclusion, hyperglycemia, but not hypoxia, is a major cause of oxidative stress in diabetic peripheral nerve. Free radical production in PNS is dependent on the degree of hypoxia, and is not initiated by relatively mild hypoxia in early diabetes.