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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Davidson, E. P. Dunlap, J. A. Gellett, J. S. Yorek, M. A. Salvemini, D. Coppey, L. J. Lund, D. D. |
| Description | Author Affiliation: Coppey LJ ( Veterans Affairs Medical Center, Diabetes Endocrinology Research Center and Department of Internal Medicine, University of Iowa, Iowa City, IA 52246, USA.) |
| Abstract | 1. To further explore the effect of antioxidants in preventing diabetes-induced vascular and neural dysfunction we treated streptozotocin-induced diabetic rats daily with subcutaneous injections of 10 mg kg(-1) of M40403 (n=11) and compared the results obtained from 17 control rats and 14 untreated diabetic rats. M40403 is a manganese(II) complex with a bis(cyclo-hexylpyridine)-substituted macrocyclic ligand that was designed to be a selective functional mimetic of superoxide dismutase. Thus, M40403 provides a useful tool to evaluate the roles of superoxide in disease states. 2. Treatment with M40403 significantly improved diabetes-induced decrease in endoneurial blood flow, acetylcholine-mediated vascular relaxation in arterioles that provide circulation to the region of the sciatic nerve, and motor nerve conduction velocity (P<0.05). M40403 treatment also reduced the appearance of superoxide in the aorta and epineurial vessels and peroxynitrite in epineurial vessels. Treating diabetic rats with M40403 reduced the diabetes-induced increase in thiobarbituric acid reactive substances in serum but did not prevent the decrease in lens glutathione level. Treating diabetic rats with M40403 did not improve sciatic nerve Na(+)/K(+) ATPase activity or the sorbitol, fructose or myo-inositol content of the sciatic nerve. 3. These studies provide additional evidence that diabetes-induced oxidative stress and the generation of superoxide and perhaps peroxynitrite may be partially responsible for the development of diabetic vascular and neural complications. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 1 |
| Volume Number | 134 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2001-09-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Diabetes Mellitus, Experimental Drug Therapy Neural Conduction Drug Effects Organometallic Compounds Pharmacology Sciatic Nerve Tyrosine Analogs & Derivatives Acetylcholine Animals Blood Glucose Metabolism Blood Vessels Physiopathology Body Weight Dose-Response Relationship, Drug Fatty Acids, Nonesterified Blood Fructose Inositol Manganese Rats, Sprague-Dawley Regional Blood Flow Blood Supply Sodium-Potassium-Exchanging ATPase Sorbitol Superoxides Thiobarbituric Acid Reactive Substances Triglycerides Vasodilation Vasodilator Agents Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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