Allopurinol, uric acid, and oxidative stress in cardiorenal disease

Abstract

In humans, the hepatic end product of purine metabolism is uric acid. Serum uric acid levels physiologically and gradually rise during human lifetime. Hyperuricemia also arises from excess dietary purine or ethanol intake, decreased renal excretion of uric acid, tumor lysis in lymphoma, leukemia or solid tumors, and sometimes pharmacotherapy. The definition of hyperuricemia is currently arbitrary. Hyperuricemia is associated with chronic kidney disease, arterial hypertension, coronary artery and heart disease, cerebrovascular disease and diabetes mellitus. Xanthine oxidase, a hepatic enzyme, catalyzes the production of uric acid, nitric oxide, and reactive oxygen species, which potentially damage deoxyribonucleic acid, ribonucleic acid and proteins, inactivate enzymes, oxidize amino acids and convert poly-unsaturated fatty acids to lipids. This is believed to contribute to atherosclerosis, endothelial dysfunction, renovascular hypertension, and cardiovascular disease. Xanthine oxidase inhibition efficiently blocks uric acid generation, and this improves glomerular filtration rates, systemic blood pressure, and cerebro-cardiovascular outcomes. Here, data from animal, in vivo, retro- and prospective, and interventional studies are reported.

XANTHINE OXYDASE INHIBITION OF KOMBUCHA TEA IN HYPERURICEMIA INDUCED WISTAR RAT: decrease of uric acid, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine

“…12 XOR is an hepar enzyme that catalyze uric acid, nitrous oxide, and reactive oxygen species which were potent to damage deoxyribonucleic acid, ribonucleic acid and its protein, inactivated enzymes, amino acids oxidation, and peroxydation of lipids. 13 XOR can be present in two interconvertible form, i.e. XO-xanthine oxydase and XDH-xhantine dehidrogenase.…”

“…Since, hyperuricemia can also lead to myocardial destruction, therefore, this situation probably happen in hyperuricemia patients. 13 Deoxyguanosine (dG) is one of DNA component and during oxidation form 8-hydroxy-2'-deoxyguanosine (8-OHdG). Therefore, 8-OHdG is a product of DNA oxidation cause by ROS.…”

Rutin inhibits coronary heart disease through ERK1/2 and Akt signaling in a porcine model

“…It poses a great threat to human health and life due to its characteristics of emergent onset, further complications and a high mortality rate (18,19). The morbidity and mortality of coronary heart disease in China has been gradually rising, and the rate of increase appears to be escalating (20,21). In the present study of a porcine model of CHD, rutin treatment significantly increased the LVEF, reduced the LVID, attenuated the increase in urine protein concentration, BUN and Scr expression levels induced by CHD, and limited the area of infarcted myocardium.…”

Uric Acid and Renal Function

“…Finally, several drugs alter UA handling by the kidney, for example drug therapy with candesartan (Li et al, 2008) or both loop-and thiazide diuretics, all of which increase the net urate reabsorption (Suliman et al, 2006). In the majority of individuals, hyperuricemia will be asymptomatic, but as UA tends to precipitate in tissues and in other body fluids, persistent hyperuricemia may eventually lead to the accumulation of urate crystals in many places, resulting in either acute painful conditions, like gout/tophaceous gout/gouty arthritis, urolithiasis, or, in severe cases, like tumor lysis syndrome, in acute UA nephropathy (Riegersperger et al, 2011). In recent years, increased fructose intake, particularly via sweetened beverages, started to attract more attention from the medical community.…”