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Abstract
Hyperuricemia, as a manifestation of a disorder of purine metabolism in insulin-resistance syndrome (IRS), is considered both a marker of IRS and a pathogenetic factor that promotes development of endothelial dysfunctions, a disturbances of pancreatic beta cells, kidney etc. functions. Uric acid (UA) is the end product of purine compounds oxidation by xantine oxidase. Since the acceptor of electrons (cofactor of xantine oxidase) is NAD+, it can be
assumed that deficiency in this purine derivate will lead to a transfer of electrons to oxygen with formation of free radicals – the factors of oxidative stress. The purpose of the work was to study the interactions between UA dysmetabolism and NAD+ content (as energy substrate and coenzyme of xantinoxidase) in various tissues of rats with experimental IRS induced by fructose diet. It is shown that in rats, after 8 weeks of 10% fructose solution using drinking water,
development of insulin resistance and hyperuricemia was accompanied by a decrease in NAD+ level, being especially expressed in the liver compared to kidneys, heart and brain. Moreover, a decline in NAD+ in the liver and an increased UA serum concentration, as well as a reduction in Na+,K+-ATPase activity in brain synaptosomes, were more expressed in males, while females were more resistant to changes in energy processes and to an increased uricemia in experimental IRS.
References
2. Ford E.S. Risk for all-cause mortality, cardiovascular disease, and diabetes associated with the metabolic syndrome: a summary of the evidence // Diabetes Care. 2005, 28, 1769-1778.
3. Kahn R., Buse J., Ferranini E. et al. The metabolic syndrome: time for a critical appraisal: joint statement from the American Diabetes Association for the study of Diabetes // Diabetes Care. 2005, 28, 2289-2304.
4. Bonora E., Bonadonna R. Hyperinsulinemia and insulin resistance are independently associated with plasma lipids, uric acid and blood pressure in nondiabetic subjects // Diabetol. 2002, 38th EASD Congr. PS567, A184.
5. Shinozaki K., Ayajiki K., Nishio Y. et al. Evidence for a causal role of the renin-angiotensin system in vascular dysfunction associated with insulin resistance // Hypertension. 2004, 43, 255-262.
6. Toma I., Kang J.J., Meer E. et al. Uric acid triggers renin release via a macula densa-dependent pathway // J. Am. Soc. Nephrol. 2007, 18, 156A.
7. Nagahama K., Inoue T., Iseki K. et al. Hyperuricemia as a predictor of hypertension in a screened cohort in Okinawa, Japan // Hypertens. Res. 2004, 27, 835-841.
8. Nakagawa T., Mazzali M., Kang D.H. et al. Hyperuricemia causes glomerular hypertrophy in the rat // Am. J. Nephrol. 2003, 23, 2-7.
9. Puig J.G., Ruilope L.M. Uric acid as a cardiovascular risk factor in arterial hypertension // J. Hypertens. 1999, 17, 869-872.
10. Pristos C.A. Cellular distribution, metabolism and regulation of xantine oxidoreductase enzyme system // Chem. Biol. Interact. 2000, 129, N 1, 195-208.
11. Matsumoto S., Koshiishi I., Inoguchi T. et al. Confirmation of superoxide generation via xantine oxidase in streptosotocin-induced diabetic mice // Free Radic. Res. 2003, 37, N 7, 767-772.
12. Demirbag R., Yilmaz R., Erel O. The association of total antioxidant capacity with sex hormones // Scand. Cardiovasc J. 2005, 39, 172-176.
13. Patterson R.A., Horsley E.T., Leake D.S. et al. Prooxidant and antioxidant properties of human serum ultrafiltrates toward LDL: Important role of uric acid // J. Lipid. Res. 2003, 44, 512-521.
14. Hayden M.R., Tyagi S.C. Uric acid: A new look at an old risk marker for cardiovascular disease, metabolic syndrome, and type 2 diabetes mellitus: The urate redox shuttle // Nutr. Metab. (Lond). 2004, 1, 10-308.
15. Kuzkaya N., Weissmann N., Harrison D. et al. Interactions of peroxynitrite with uric acid in the presence of ascorbate and thiols: implications for uncoupling endothelial nitric oxide synthase // Biochem. Pharm. 2005, 70, 343-354.