Effect of a potent new aldose reductase inhibitor, (5-(3-thienyltetrazol-1-yl)acetic acid (TAT), on diabetic neuropathy in rats.
(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose reductase inhibitor, was administered for 4 weeks to rats with streptozotocin-induced diabetes. Physiological and biochemical studies were subsequently conducted on rat nerve tissue and erythrocyte sorbitol content was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic controls (NC). A significant delay in caudal motor nerve conduction velocity (MNCV) and significantly higher glucose, sorbitol and fructose values were observed in the sciatic nerve, accompanied by a markedly higher sorbitol concentration in erythrocytes. In contrast, TAT-treated diabetic groups (DT-10, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve sorbitol and fructose levels and erythrocyte sorbitol concentration than the DC group. There were good correlations between SNBF and MNCV (r = 0.672, P < 0.001) and between SNBF and erythrocyte sorbitol (r = 0.455, P < 0.003). These findings suggest that both vascular and metabolic factors play an important role in diabetic neuropathy and the effect of aldose reductase inhibitors on diabetic neuropathy may be mediated by at least these two factors.
Hotta
N
N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Kakuta
H
H
Fukasawa
H
H
Koh
N
N
Sakakibara
F
F
Nakamura
J
J
Hamada
Y
Y
Wakao
T
T
Hara
T
T
Mori
K
K
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology / Q000517:prevention & control*; D004912:Erythrocytes / Q000378:metabolism; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007294:Inositol / Q000378:metabolism; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D010525:Peripheral Nerves / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012044:Regression Analysis; D012584:Sciatic Nerve / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D013012:Sorbitol / Q000097:blood / Q000378:metabolism; D013623:Tail / Q000294:innervation; D013777:Tetrazoles / Q000627:therapeutic use*; D013876:Thiophenes / Q000627:therapeutic use*; D013997:Time Factors
D001786:Blood Glucose; D013777:Tetrazoles; D013876:Thiophenes; C080974:(5-(3-thienyl)tetrazol-1-yl)acetic acid; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose