Impaired nerve regeneration in streptozotocin-diabetic rats. Effects of treatment with an aldose reductase inhibitor.
Rats with streptozotocin-induced diabetes have a decreased rate of sciatic nerve regeneration. We studied the effects on this defect of treatment with the aldose reductase inhibitor, ponalrestat (25 mg/kg per day via an endogastric tube). The nerves of diabetic rats were crush-injured at 5 weeks of diabetes and regeneration evaluated 7 days later with the pinch-reflex test. Ponalrestat treatment was started at day 3 after streptozotocin injection and was continued for the whole experimental period, i.e. until 6 weeks of diabetes. The treatment prevented effectively the accumulation of sorbitol and fructose in the nerves of diabetic rats, but was without effect on the sciatic nerve regeneration (controls 21.8 +/- 1.2 mm/7 days (mean +/- SEM, n = 6), untreated diabetics 15.8 +/- 1.8 (n = 7), ponalrestat-treated diabetics 16.2 +/- 1.0 (n = 10]. The results indicate that there is no connection between increased sorbitol pathway flux and impaired regeneration in streptozotocin diabetic rats.
Ekström
A R
AR
Department of Zoophysiology, University of Lund, Sweden.
Tomlinson
D R
DR
D000449:Aldehyde Reductase / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D009409:Nerve Crush; D009416:Nerve Regeneration; D010793:Phthalazines / Q000627:therapeutic use*; D011724:Pyridazines / Q000627:therapeutic use*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin; D013401:Sugar Alcohol Dehydrogenases / Q000502:physiology*
D004791:Enzyme Inhibitors; D010793:Phthalazines; D011724:Pyridazines; C042829:ponalrestat; D013311:Streptozocin; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase