Effects of aldose reductase inhibitor sorbinil on neuroaxonal dystrophy and levels of myo-inositol and sorbitol in sympathetic autonomic ganglia of streptozocin-induced diabetic rats.
Biochemical and ultrastructural effects of the aldose reductase inhibitor sorbinil were examined in two experimental rat models of chronic diabetic neuropathy: rats with streptozocin-induced diabetes (STZ-D) and rats fed a galactose-enriched diet. The frequency of neuroaxonal dystrophy in the superior mesenteric sympathetic ganglia of rats with untreated 8-mo STZ-D increased sevenfold compared with that in age-matched controls. Animals chronically maintained on a diet containing 50% galactose, however, did not develop neuroaxonal dystrophy in excess of that found in untreated age-matched control rats. Institution of sorbinil therapy at the time of induction of STZ-D decreased, but did not completely normalize, the frequency of neuroaxonal dystrophy without altering the severity of diabetes; this finding is based on measurements of plasma glucose, body weight, food consumption, 24-h urine volume, and levels of glycosylated hemoglobin. Sorbitol levels in the superior cervical sympathetic ganglia (SCG) of untreated 8-mo-diabetic animals increased three- to fourfold compared with levels in controls. The increase in sorbitol content of diabetic SCG was completely prevented by early institution of dietary sorbinil therapy. The myo-inositol content of 8-mo-diabetic SCG was modestly decreased compared with controls. Sorbinil administration improved but did not completely normalize diabetic SCG myo-inositol. The sorbitol content of the SCG, superior mesenteric and celiac sympathetic ganglia, and a major trunk of the superior mesenteric nerve of short-term (2.5-mo)-diabetic rats increased comparably, but only the diabetic SCG showed a decrease in myo-inositol.
Schmidt
R E
RE
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Plurad
S B
SB
Sherman
W R
WR
Williamson
J R
JR
Tilton
R G
RG
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001369:Axons / Q000032:analysis / Q000648:ultrastructure; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism* / Q000473:pathology; D005690:Galactose / Q000494:pharmacology; D005728:Ganglia, Sympathetic / Q000032:analysis* / Q000648:ultrastructure; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007294:Inositol / Q000032:analysis*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000032:analysis*; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D007093:Imidazoles; D048289:Imidazolidines; D007294:Inositol; D013012:Sorbitol; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase; C026411:sorbinil; D005690:Galactose