The effects of sorbinil on peripheral nerve conduction velocity, polyol concentrations and morphology in the streptozotocin-diabetic rat.
This study examined the effects of an aldose reductase inhibitor, Sorbinil, on neuropathy over a 6-month period in streptozotocin-diabetic rats. Sorbinil treatment prevented the 10-fold increase in nerve sorbitol found with diabetes. It produced a 60% improvement in tibial nerve motor conduction velocity after 6 months. Morphometric profiles of nerves were also normalized. Axon area was reduced by 14% in untreated diabetic rats compared to age-matched controls, whereas Sorbinil-treated animals showed normal age-related axon growth. Myelin area was increased by 28% in untreated diabetic animals, but was the same as age-matched controls with Sorbinil treatment. Nerve myo-inositol levels were reduced by 45% after three months of untreated diabetes, but were normal after six months. Sorbinil treatment tended to restore myo-inositol levels toward normal over the shorter time period. It was concluded that axon growth retardation is the most likely cause of the conduction deficit seen in long-term experimental diabetes.
D000367:Age Factors; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001369:Axons / Q000473:pathology; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007294:Inositol / Q000032:analysis; D008297:Male; D009186:Myelin Sheath / Q000473:pathology; D009431:Neural Conduction / Q000187:drug effects*; D010525:Peripheral Nerves / Q000032:analysis / Q000187:drug effects* / Q000473:pathology; D011108:Polymers / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000032:analysis; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D011108:Polymers; C024617:polyol; D007294:Inositol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil