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Sulindac in established experimental diabetes: a follow-up study
P van der Sloot1, A Mizisin, D Zochodne
1Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
Summary
Sulindac treatment modestly improved nerve conduction in some areas for diabetic rats, but did not reverse established biochemical changes. Further research into reversal strategies for diabetic neuropathy is recommended.
Area of Science:
- Neuroscience
- Pharmacology
- Diabetology
Background:
- Previous studies showed nonsteroidal anti-inflammatory drugs prevented nerve abnormalities in experimental diabetes.
- Sulindac, an inhibitor of cyclo-oxygenase and aldose reductase, was investigated for potential benefits in diabetic neuropathy.
Purpose of the Study:
- To determine if sulindac treatment could reverse or improve established electrophysiological and biochemical abnormalities in experimental diabetes.
- To assess the efficacy of sulindac in a 3-month duration model of experimental diabetes.
Main Methods:
- Diabetic rats with 3 months of diabetes were treated with sulindac (6.0 mg/kg, 5/7 days weekly) for 1 month.
- Conduction velocity, sciatic sugars, and polyols were measured and compared between sulindac-treated diabetic rats, untreated diabetic rats, and control groups.
Main Results:
- Diabetic rats exhibited slowed nerve conduction velocity in multiple nerve fibers.
- Sulindac treatment improved caudal motor and sural sensory nerve conduction velocity, but not caudal sensory or sciatic tibial motor conduction.
- Sulindac did not significantly alter sciatic sugars or polyols in diabetic rats.
Conclusions:
- Sulindac demonstrated modest efficacy in reversing some electrophysiological deficits of experimental diabetic neuropathy.
- The observed efficacy was less pronounced than in previous preventative studies.
- The study highlights the importance of investigating reversal paradigms for all experimental diabetic neuropathy therapies.