Preventive effect of long-term aldose reductase inhibition (ponalrestat) on nerve conduction and sural nerve structure in the spontaneously diabetic Bio-Breeding rat

The Journal of Clinical Investigation
A A SimaD A Greene

Abstract

To test the hypothesis that aldose reductase inhibition may prevent or delay the development of functional and structural neuropathy in the insulin-deficient diabetic Bio-Breeding rat (BB-rat), hyperglycemic rats were begun on the aldose reductase inhibitor (ARI) ponalrestat 25 mg/kg body wt soon after the onset of diabetes and followed for 4 or 6 mo. Ponalrestat treatment completely prevented the characteristic nerve conduction slowing and structural abnormalities of the node of Ranvier for 4 mo despite only partial preservation of axonal integrity. Ponalrestat treatment for 6 mo achieved a partial but significant prevention of nerve conduction slowing, axoglial dysjunction, and axonal degenerative changes. This incomplete but significant prevention of neuropathy by ponalrestat suggests that additional mechanisms besides polyol-pathway activation may be of importance in the pathogenesis of diabetic neuropathy. Alternatively, the dosage used in the present study may not have been sufficient to achieve a complete prevention. Despite the only partial protective effect of ARI treatment on degenerative peripheral nerve changes in hyperglycemic BB-rats, 6 mo of treatment resulted in a more than threefold increase in regenerating ner...Continue Reading

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Citations

Oct 12, 2000·Diabetes/metabolism Research and Reviews·K SugimotoA A Sima
Mar 1, 1991·Diabetes/metabolism Reviews·G PuglieseJ R Williamson
Apr 1, 1992·Diabetes/metabolism Reviews·L CrisáA A Rossini
Apr 1, 1992·Diabetes/metabolism Reviews·D R Tomlinson
Oct 1, 1993·Diabetes/metabolism Reviews·D A GreeneS A Lattimer
Oct 1, 1995·Diabetes/metabolism Reviews·S Yagihashi
May 1, 1995·Diabetologia·G MoreoG B Colucci
Jan 1, 1992·Pharmacology & Therapeutics·D R TomlinsonA L Carrington
Jan 5, 1995·Biochimica Et Biophysica Acta·D A CarperS E Old
Apr 1, 1995·Diabetes Research and Clinical Practice·M SensiD Andreani
Jan 1, 1995·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·N Hotta
Jul 23, 1998·The Surgical Clinics of North America·S P O'BrienM D Kerstein
Feb 1, 2003·Clinical Neurophysiology : Official Journal of the International Federation of Clinical Neurophysiology·Satoshi Kuwabara
Apr 1, 1993·Diabetic Medicine : a Journal of the British Diabetic Association·D R Tomlinson
Aug 1, 1993·Diabetic Medicine : a Journal of the British Diabetic Association·N E Cameron, M A Cotter
Jan 1, 1993·Diabetic Medicine : a Journal of the British Diabetic Association·D A Greene, A A Sima
Oct 30, 2010·Circulation Research·Ferdinando Giacco, Michael Brownlee
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May 10, 2007·The Review of Diabetic Studies : RDS·Petr Boucek
Jan 1, 2014·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Randhir SinghNavpreet Kaur
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Oct 1, 1992·Biochemical Medicine and Metabolic Biology·A Bhatnagar, S K Srivastava

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