The aim of the present work was to study the effect of 3- mercapto-5H-1,2,4-triazino[5,6-b]indole-5-acetic acid (CMTI), an efficient aldose reductase inhibitor, on sorbitol accumulation in selected organs of streptozotocin-induced diabetic rats in vivo . In addition, the effect of CMTI on aldose reductase back reaction and on sorbitol dehydrogenase was determined. The model of experimental diabetes in male Wistar rats induced by streptozotocin was used. Experimental diabetes was induced by triple intraperitoneal doses of streptozotocin on three consecutive days. In diabetic rats, significant elevation of sorbitol concentration in the sciatic nerve and eye lenses was recorded. CMTI administered intragastrically (50 mg/kg/day) for five consecutive days significantly inhibited sorbitol accumulation in the sciatic nerve, yet it was without effect in eye lenses of diabetic animals. For aldose reductase back reaction, the substrate affinity of glycerol to aldose reductase was one order lower than that of glyceraldehyde in forward reaction. In addition, the back reaction was much slower, characterized by Vmax value of about 30 times lower than that of the forward reaction. Inhibition of aldose reductase by CMTI was characterized by closely related IC50 values in submicromolar range for both forward and back reactions. No significant inhibition of the second enzyme of the polyol pathway, sorbitol dehydrogenase, by 100 μM CMTI was recorded (I=0.9±2.7 %, n=3). To conclude, the presented results showed the ability of CMTI to affect the polyol pathway in diabetic rats in vivo and represent thus a further step in a complex preclinical evaluation of CMTI as a potential agent for treatment of chronic diabetic complications., M. Soltesova Prnova, J. Ballekova, A. Gajdosikova, A. Gajdosik, M. Stefek., and Obsahuje bibliografii
The study aimed to evaluate if the monitoring of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), lipoperoxides (LPO) and interleukin-6 (IL-6) in plasma could help to predict development of diabetic complications (DC). Clinical and biochemical parameters including AGEs, AOPP, LPO and IL-6 were investigated in patients with type 2 diabetes mellitus (DM2) with (+DC) and without (-DC) complications. AGEs were significantly higher in both diabetic groups compared to controls. AGEs were also significantly higher in group +DC compared to -DC. AGEs significantly correlated with HbA1c. We observed significantly higher AOPP in both diabetic groups in comparison with controls, but the difference between -DC and +DC was not significant. LPO significantly correlated with BMI. IL-6 were significantly increased in both diabetic groups compared to controls, but the difference between -DC and +DC was not significant. There was no significant correlation between IL-6 and clinical and biochemical parameters. These results do not exclude the association between IL-6 and onset of DC. We suggest that the measurement of not only HbA1c, but also AGEs may be useful to predict the risk of DC development in clinical practice. Furthermore, the measurement of IL-6 should be studied as adjunct to HbA1c monitoring., V. Jakuš, E. Šándorová, J. Kalninová, B. Krahulec., and Obsahuje bibliografii