PMID- 2110189
OWN - NLM
STAT- MEDLINE
DCOM- 19900606
LR  - 20221207
IS  - 0021-9738 (Print)
IS  - 0021-9738 (Linking)
VI  - 85
IP  - 5
DP  - 1990 May
TI  - Preventive effect of long-term aldose reductase inhibition (ponalrestat) on nerve 
      conduction and sural nerve structure in the spontaneously diabetic Bio-Breeding 
      rat.
PG  - 1410-20
AB  - 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 nerve fibers. These data suggest 
      that prophylactic ARI treatment may be efficacious in delaying the development of 
      diabetic neuropathy.
FAU - Sima, A A
AU  - Sima AA
AD  - Department of Pathology, University of Manitoba, Winnipeg, Canada.
FAU - Prashar, A
AU  - Prashar A
FAU - Zhang, W X
AU  - Zhang WX
FAU - Chakrabarti, S
AU  - Chakrabarti S
FAU - Greene, D A
AU  - Greene DA
LA  - eng
GR  - DK-38304/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Phthalazines)
RN  - 0 (Pyridazines)
RN  - 2CV0A5G64E (ponalrestat)
RN  - EC 1.1.- (Sugar Alcohol Dehydrogenases)
RN  - EC 1.1.1.21 (Aldehyde Reductase)
SB  - IM
MH  - Aldehyde Reductase/*antagonists & inhibitors
MH  - Animals
MH  - Axons/ultrastructure
MH  - Blood Glucose/analysis
MH  - Diabetes Mellitus, Experimental/*drug therapy/physiopathology
MH  - Diabetic Neuropathies/pathology/physiopathology/*prevention & control
MH  - Glycated Hemoglobin/analysis
MH  - Male
MH  - Microscopy, Electron
MH  - Motor Neurons/drug effects/*physiology
MH  - Nerve Fibers, Myelinated/drug effects/ultrastructure
MH  - Neural Conduction/*drug effects
MH  - Phthalazines/*therapeutic use
MH  - Prediabetic State/*drug therapy/physiopathology
MH  - Pyridazines/*therapeutic use
MH  - Ranvier's Nodes/pathology/physiology
MH  - Rats
MH  - Rats, Inbred BB
MH  - Reference Values
MH  - Spinal Nerves/*physiopathology
MH  - Sugar Alcohol Dehydrogenases/*antagonists & inhibitors
MH  - Sural Nerve/drug effects/*physiopathology
PMC - PMC296586
EDAT- 1990/05/01 00:00
MHDA- 1990/05/01 00:01
PMCR- 1990/05/01
CRDT- 1990/05/01 00:00
PHST- 1990/05/01 00:00 [pubmed]
PHST- 1990/05/01 00:01 [medline]
PHST- 1990/05/01 00:00 [entrez]
PHST- 1990/05/01 00:00 [pmc-release]
AID - 10.1172/JCI114585 [doi]
PST - ppublish
SO  - J Clin Invest. 1990 May;85(5):1410-20. doi: 10.1172/JCI114585.