Sulindac in established experimental diabetes: a follow-up study.
BACKGROUND
In two previous studies we have demonstrated prevention of electrophysiological abnormalities of nerve in experimental STZ (streptozotocin)-induced diabetes (ED) of rats using nonsteroidal anti-inflammatory agents: indomethacin and sulindac. Sulindac might benefit ED because it inhibits both cyclo-oxygenase and aldose reductase.


METHODS
In this work, we examined whether 1 month of sulindac treatment reversed or improved established biochemical and electrophysiological abnormalities in experimental diabetes of 3 months duration. Sulindac-treated diabetic rats (6.0 mg/kg 5/7 days weekly by gavage) were compared to untreated diabetics, nondiabetic controls and sulindac treated control rats.


RESULTS
Diabetic rats developed slowing of conduction velocity in caudal sensory, sural sensory, caudal motor and sciatic tibial motor fibers. Sulindac improved caudal motor and, to a lesser extent sural sensory conduction but not caudal sensory or sciatic tibial motor conduction. Sulindac did not alter sciatic sugars or polyols.


CONCLUSIONS
Sulindac provided modest improvement in some indices of experimental neuropathy in this reversal study, but there was less efficacy than in the preventative study. Reversal paradigms should be examined in all experimental therapies for diabetic neuropathy.
Department of Clinical Neurosciences, University of Calgary, Alberta, Canada.
P
P
van der Sloot
A
A
Mizisin
D
D
Zochodne
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced*; D004195:Disease Models, Animal; D004594:Electrophysiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005500:Follow-Up Studies; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013467:Sulindac / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D013467:Sulindac