دورية أكاديمية
An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense.
| العنوان: | An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense. |
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| المؤلفون: | Obrosova IG; Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, Michigan 48109-0354, USA. iobrosso@umich.edu, Van Huysen C, Fathallah L, Cao XC, Greene DA, Stevens MJ |
| المصدر: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2002 Jan; Vol. 16 (1), pp. 123-5. Date of Electronic Publication: 2001 Nov 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Federation of American Societies for Experimental Biology Country of Publication: United States NLM ID: 8804484 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1530-6860 (Electronic) Linking ISSN: 08926638 NLM ISO Abbreviation: FASEB J Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2020- : [Bethesda, Md.] : Hoboken, NJ : Federation of American Societies for Experimental Biology ; Wiley Original Publication: [Bethesda, Md.] : The Federation, [c1987- |
| مواضيع طبية MeSH: | Imidazolidines*, Aldehyde Reductase/*antagonists & inhibitors , Diabetes Mellitus, Experimental/*drug therapy , Diabetic Neuropathies/*drug therapy , Enzyme Inhibitors/*pharmacology , Imidazoles/*pharmacology, Animals ; Antioxidants/metabolism ; Cytosol/drug effects ; Cytosol/metabolism ; Diabetes Mellitus, Experimental/metabolism ; Diabetes Mellitus, Experimental/physiopathology ; Diabetic Neuropathies/metabolism ; Diabetic Neuropathies/physiopathology ; Enzyme Inhibitors/administration & dosage ; Imidazoles/administration & dosage ; Lipid Peroxidation/drug effects ; Mitochondria/drug effects ; Mitochondria/metabolism ; Models, Biological ; NAD/metabolism ; Neural Conduction/drug effects ; Oxidation-Reduction/drug effects ; Oxidative Stress ; Peripheral Nerves/drug effects ; Peripheral Nerves/metabolism ; Peripheral Nerves/physiopathology ; Rats |
| مستخلص: | Aldose reductase inhibitors (ARIs) prevent peripheral nerve dysfunction and morphological abnormalities in diabetic animal models. However, some experimental intervention studies and clinical trials of ARIs on diabetic neuropathy appeared disappointing because of either 1) their inadequate design and, in particular, insufficient correction of the sorbitol pathway activity or 2) the inability to reverse established functional and metabolic deficits of diabetic neuropathy by AR inhibition in general. We evaluated whether diabetes-induced changes in nerve function, metabolism, and antioxidative defense are corrected by the dose of ARI (sorbinil, 65 mg/kg/d in the diet), resulting in complete inhibition of increased sorbitol pathway activity. The groups included control rats and streptozotocin-diabetic rats treated with/without ARI for 2 weeks after 4 weeks of untreated diabetes. ARI treatment corrected diabetes-induced nerve functional changes; that is, decrease in endoneurial nutritive blood flow, motor and sensory nerve conduction velocities, and metabolic abnormalities (i.e., mitochondrial and cytosolic NAD+/NADH redox imbalances and energy deficiency). ARI restored nerve concentrations of two major non-enzymatic antioxidants, reduced glutathione (GSH) and ascorbate, and completely arrested diabetes-induced lipid peroxidation. In conclusion, treatment with adequate doses of ARIs (that is, doses that completely inhibit increased sorbitol pathway activity) is an effective approach for reversal of, at least, early diabetic neuropathy. |
| المشرفين على المادة: | 0 (Antioxidants) 0 (Enzyme Inhibitors) 0 (Imidazoles) 0 (Imidazolidines) 0U46U6E8UK (NAD) EC 1.1.1.21 (Aldehyde Reductase) G4186B906P (sorbinil) |
| تواريخ الأحداث: | Date Created: 20011116 Date Completed: 20020131 Latest Revision: 20220318 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1096/fj.01-0603fje |
| PMID: | 11709499 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1530-6860 |
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| DOI: | 10.1096/fj.01-0603fje |