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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Characterization of a novel aldose reductase inhibitor, TAT, and its effects on streptozotocin-induced diabetic neuropathy in rats.

TAT ([5-(3-thienyl)tetrazol-1-yl]acetic acid) is a novel aldose reductase ( AR) inhibitor. It exhibited highly potent inhibition of partially purified AR from rat lens (IC50 = 2.1 x 10(-8) M), rabbit lens (IC50 = 2.3 x 10(-8) M) and human placenta (IC50 = 2.8 x 10(-8) M). On the other hand, TAT had a weak inhibitory activity against mouse liver aldehyde reductase ( ALR) (IC50 = 2.4 x 10(-6) M) and poor inhibitory activity against several adenine nucleotide-requiring enzymes. Against rat lens AR, TAT exhibited an uncompetitive inhibition at a concentration of 1.0 x 10(-8) M and a mixed type inhibition at higher concentrations. TAT inhibited sorbitol accumulation in the isolated rat sciatic nerve (IC50 = 1.0 x 10(-6) M), rat lens (IC50 = 5.7 x 10(-6) M), human erythrocytes (IC50 = 2.5 x 10(-7) M), and rabbit erythrocytes (IC50 = 2.1 x 10(-7) M) incubated with high glucose concentrations. The oral administration of TAT (5-100 mg/kg/day) to streptozotocin (STZ)-induced diabetic rats during a 5-day treatment period decreased the sorbitol content in the sciatic nerve, dose-dependently (ED50: 8.8 mg/kg/day for the prevention and 9.0 mg/kg/day for the reversal). Moreover, TAT (2.5-40 mg/kg/day) improved the decreased motor nerve conduction velocity (MNCV) after a 14-day treatment period. There was a significant correlation between MNCV and sciatic nerve sorbitol content. From these results, TAT is expected to be useful for the clinical treatment of diabetic complications.[1]

References

  1. Characterization of a novel aldose reductase inhibitor, TAT, and its effects on streptozotocin-induced diabetic neuropathy in rats. Inukai, S., Agata, M., Sato, M., Naitou, A., Matsukawa, H., Goto, M. Jpn. J. Pharmacol. (1993) [Pubmed]
 
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