Prevention of defects of axonal transport and nerve conduction velocity by oral administration of myo-inositol or an aldose reductase inhibitor in streptozotocin-diabetic rats.
The effects of orally-administered myo-inositol have been compared with those of an aldose reductase inhibitor on acute neurological defects in experimentally diabetic rats. Three groups of streptozotocin-treated diabetic rats (50 mg/kg, IP) together with three groups of age-matched controls (saline, IP) were compared. One pair of groups (control and diabetic) were untreated for 3 weeks, another pair of groups received daily oral myo-inositol (667 mg/kg) and the third pair received an aldose reductase inhibitor (ICI 105 552; 50 mg . kg-1, day-1, orally). The untreated diabetic group showed statistically significant deficits in accumulation, proximal to 24 h sciatic nerve constrictions, of choline acetyltransferase activity by comparison with untreated controls (2.8 +/- 0.4 versus 5.1 +/- 0.4 nmol acetylcholine . h-1 . nerve-1; p less than 0.001). The untreated diabetic rats also showed a fall in motor nerve conduction velocity of 6.2 +/- 0.7 m/s which was statistically significant (p less than 0.001). Treatment of the diabetic group with myo-inositol prevented the development of both defects of axonal transport and conduction velocity; both measurements were similar to those of the myo-inositol treated control rats. Likewise the diabetic rats which received aldose reductase inhibitor showed prevention of both defects. Nerves from untreated diabetic rats showed marked sorbitol accumulation and a statistically significant reduction in myo-inositol content by comparison with the untreated controls (sorbitol, 1.56 +/- 0.22 versus 0.8 +/- 0.01 and myo-inositol, 1.47 +/- 0.10 versus 2.3 +/- 0.10 nmol/mg; p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D001786:Blood Glucose / Q000032:analysis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology* / Q000517:prevention & control; D007294:Inositol / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects*; D011804:Quinolines / Q000627:therapeutic use*; D015363:Quinolones; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000187:drug effects / Q000503:physiopathology*; D013012:Sorbitol / Q000378:metabolism; D013311:Streptozocin; D013401:Sugar Alcohol Dehydrogenases / Q000037:antagonists & inhibitors*
D001786:Blood Glucose; D011804:Quinolines; D015363:Quinolones; D007294:Inositol; D013012:Sorbitol; D013311:Streptozocin; C033661:ICI 105552; D013401:Sugar Alcohol Dehydrogenases; D000449:Aldehyde Reductase