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Titolo:
An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense
Autore:
Obrosova, IG; Van Huysen, C; Fathallah, L; Cao, XH; Greene, DA; Stevens, MJ;
Indirizzi:
Univ Michigan, Med Ctr, Dept Internal Med, Div Endocrinol & Metab, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 nol & Metab, Ann Arbor, MI 48109 USA Vet Adm Med Ctr, Ann Arbor, MI 48105 USA Vet Adm Med Ctr Ann Arbor MI USA48105 m Med Ctr, Ann Arbor, MI 48105 USA
Titolo Testata:
FASEB JOURNAL
fascicolo: 13, volume: 15, anno: 2001,
pagine: NIL_162 - NIL_187
SICI:
0892-6638(200111)15:13<NIL_162:AARIRE>2.0.ZU;2-5
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE-C; ENDONEURIAL BLOOD-FLOW; ALPHA-LIPOIC ACID; CONDUCTION-VELOCITY; ENERGY-METABOLISM; SCIATIC-NERVE; SORBITOL DEHYDROGENASE; OXIDATIVE STRESS; POLYOL PATHWAY; NITRIC-OXIDE;
Keywords:
diabetic neuropathy; NAD(+)/NADH ratio; nerve blood flow; nerve conduction; oxidative stress; reversal;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
103
Recensione:
Indirizzi per estratti:
Indirizzo: Obrosova, IG Univ Michigan, Med Ctr, Dept Internal Med, Div Endocrinol & Metab, 1150 W Med Ctr Dr,MSRB 2,Room 5570, Ann Arbor, MI 48109 USA Univ Michigan 1150 W Med Ctr Dr,MSRB 2,Room 5570 Ann Arbor MI USA 48109
Citazione:
I.G. Obrosova et al., "An aldose reductase inhibitor reverses early diabetes-induced changes in peripheral nerve function, metabolism, and antioxidative defense", FASEB J, 15(13), 2001, pp. NIL_162-NIL_187

Abstract

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 activityor 2) the inability to reverse established functional and metabolic deficits of diabetic neuropathy by AR inhibition in general. We evaluated whetherdiabetes-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 thatcompletely inhibit increased sorbitol pathway activity) is an effective approach for reversal of, at least, early diabetic neuropathy.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/12/20 alle ore 08:46:47