title: A combination of the aldose reductase inhibitor, statil, and the prostaglandin E1 analogue, OP1206.alpha CD, completely improves sciatic motor nerve conduction velocity in streptozocin-induced chronically diabetic rats.
abstract: In view of the possible implication of multifactorial mechanisms in the pathogenesis of diabetic neuropathy, the aldose reductase inhibitor (ARI), Statil, which ameliorates abnormal sorbitol or myo-inositol metabolism in diabetic nerves, and the prostaglandin E1 (PGE1) analogue, OP1206.alpha CD (OP), which improves diabetic vascular derangements, were administered simultaneously for 2 months to streptozocin (STZ)-induced diabetic rats with 5 months' duration of diabetes, and the effects on sciatic motor nerve conduction velocity (MNCV), Na(+)-K(+)-adenosine triphosphatase (ATPase) activity, and morphology of myelinated nerve fibers (MNF) were compared with the effects of a monotherapy with OP. The combination regimen ameliorated abnormal nerve sorbitol and myo-inositol levels and normalized decreased MNCV and enzyme activity. In contrast, neither sorbitol nor myo-inositol metabolism was ameliorated, and only insufficient improvement of MNCV and morphology of MNF was obtained with a monotherapy with OP. In addition, the combination therapy reversed both a decrease in the percent of large MNF and an increase in the percent of small MNF in diabetic rats, whereas a monotherapy with OP reversed only a decrease in the percent of large MNF. The results might suggest that a multiple-drug therapy with different mechanisms of action has greater effects on diabetic neuropathy than a single-drug therapy and is worthy of clinical consideration.
authors.affiliation: Third Department of Medicine, Shiga University of Medical Science, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Yasuda
authors.forename: M
authors.initials: M
authors.lastname: Sonobe
authors.forename: T
authors.initials: T
authors.lastname: Hisanaga
authors.forename: T
authors.initials: T
authors.lastname: Kawabata
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: R
authors.initials: R
authors.lastname: Kikkawa
authors.forename: Y
authors.initials: Y
authors.lastname: Shigeta
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000527:Alprostadil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000473:pathology / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000188:drug therapy; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D007294:Inositol / Q000032:analysis; D008297:Male; D009431:Neural Conduction / Q000187:drug effects*; D010793:Phthalazines / Q000008:administration & dosage / Q000494:pharmacology*; D011459:Prostaglandins E, Synthetic / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000473:pathology / Q000503:physiopathology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis; D013012:Sorbitol / Q000032:analysis
chemical_list: D007004:Hypoglycemic Agents; D010793:Phthalazines; D011459:Prostaglandins E, Synthetic; C042829:ponalrestat; D007294:Inositol; D013012:Sorbitol; C025090:ONO 1206; D000449:Aldehyde Reductase; D000254:Sodium-Potassium-Exchanging ATPase; D000527:Alprostadil