EFFECT OF A POTENT NEW ALDOSE REDUCTASE INHIBITOR, (5-(3-THIENYL)TETRAZOL-1-YL)ACETIC ACID (TAT), ON DIABETIC NEUROPATHY IN RATS

(5-(3-Thienyl)tetrazol-1-yl)acetic acid (TAT), a novel potent aldose r eductase inhibitor, was administered for 4 weeks to rats with streptoz otocin-induced diabetes. Physiological and biochemical studies were su bsequently conducted on rat nerve tissue and erythrocyte sorbitol cont ent was estimated. Sciatic nerve blood flow (SNBF) was markedly lower (about 43.4%) in untreated diabetic (DC) rats than in non-diabetic con trols (NC). A significant delay in caudal motor nerve conduction veloc ity (MNCV) and significantly higher glucose, sorbitol and fructose val ues were observed in the sciatic nerve, accompanied by a markedly high er sorbitol concentration in erythrocytes, In contrast, TAT-treated di abetic groups (DT-IO, DT-40 and DT-200) had significantly higher SNBF, MNCV and sciatic nerve myo-inositol values and lower sciatic nerve so rbitol 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 = 0.45 5, 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.