Serum xanthine oxidase

Battelli mg, Musiani S, Valgimigli M, et al. (2001) Serum xanthine oxidase in human liver disease. Am J Gastroenterol 96-. 1194-1199. 

Giler S, Sperling O, Brosh S, et al. (1975) Serum xanthine oxidase in jaundice. Clin Chim Acta 63 37-40. 

Most patients in the United States are treated with allopurinol, which usually is effective if the dosage is titrated appropriately. The drug and its primary active metabolite, oxypurinol, reduce serum uric acid concentrations by inhibiting the enzyme xanthine oxidase, thereby blocking the oxidation of hypoxanthine and xanthine to uric acid. 

Increase in blood and urine Mo levels, increases in serum ceruloplasmin, increased xanthine oxidase activity (11) Increased uric acid, decreased copper excretion, high incidence of gout-like disease (11)... 

Allopurinol and its major metabolite, oxypurinol, are xanthine oxidase inhibitors and impair the conversion of hypoxanthine to xanthine and xanthine to uric acid. Allopurinol also lowers the intracellular concentration of PRPP. Because of the long half-life of its metabolite, allopurinol can be given once daily orally. It is typically initiated at a dose of 100 mg/day and increased by 100 mg/day at 1-week intervals to achieve a serum uric acid level of 6 mg/dL or less. Serum levels can be checked about 1 week after starting therapy or modifying the dose. Although typical doses are 100 to 300 mg daily, occasionally doses of 600 to 800 mg/day are necessary. The dose should be reduced in patients with renal insufficiency (200 mg/day for CLcr 60 mL/min or less, and 100 mg/day for CLcr 30 mL/min or less). 

In patients with severely impaired renal function or decreased urate clearance, the plasma half-life of oxipurinol is greatly prolonged. A dose of 100 mg/day or 300 mg twice a week, or less, may be sufficient to maintain adequate xanthine oxidase inhibition to reduce serum urate levels. 

The micro-hypoxanthine sensor was made by immobilizing xanthine oxidase with bovine serum albumin and glutaraldehyde on the micro-oxygen electrode (Fig. 3.18.D). The detection limit achieved was 6.7 pM and the sensitivity was ca. 10 times higher than that afforded by conventional hypo-xanthine sensors. 

Allopurinol is an xanthine oxidase inhibitor. It reduces urate production and is used in primary and secondary urate overproduction. Therapy of hyperuricemia prevents recurring attacks of acute gouty arthritis. Allopurinol dosages are 300 mg/day for serum creatinine < 1.5 mg/dl and 100 mg/day for serum creatinine between 1.6-2.0 mg/dl. Reduction of tophi is slow with allopurinol, particularly in patients with giant tophi and renal insufficiency where drug dosage is limited. 

Allopurinol, in contrast to the uricosuric drugs, reduces serum urate levels through a competitive inhibition of uric acid synthesis rather than by impairing renal urate reabsorption. This action is accomplished by inhibiting xanthine oxidase, the enzyme involved in the metabolism of hypoxanthine and xanthine to uric acid. After enzyme inhibition, the urinary and blood concentrations of uric acid are greatly reduced and there is a simultaneous increase in the excretion of the more soluble uric acid precursors, xanthine and hypoxanthine. 

Antitoxic effect. Sesame oil, adiministered to male Wistar rats, ameliorated hepatic and renal damage in a dose-dependent manner and increased survival in lipopolysaccha-ride-treated rats. It decreased lipid peroxide concentration in serum but not in liver and kidney. Serum nitrite production was unaffected by sesame oil ingestion, and the activity of xanthine oxidase was reduced in the lipopolysaccharide-challenged rats k Anti-tumor activity. Water extract of the dried seed, administered intragastrically to mice at a dose of 50 mg/animal daily for 5 days, was active on CA-Ehrlich-ascites, 18% increase in life-span. Intraperitoneal administration was active on Dalton s lyphoma and CA-Ehrlich-ascites, 19 and 39% increase in life-span, respectively ". Seed oil, administered to rats intraperito-neally with 1,2,5,6-dibenzanthracene or re-tene, was active on sarcoma ". 

Mechanism of Action A xanthine oxidase inhibitor that decreases uric acid production by inhibiting xanthine oxidase, an enzyme. Therapeutic Effect Reduces uric acid concentrations in both serum and urine. 

Allopurinol is approximately 80% absorbed after oral administration and has a terminal serum half-life of 1-2 hours. Like uric acid, allopurinol is itself metabolized by xanthine oxidase, but the resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase and has a long enough duration of action so that allopurinol is given only once a day. 

Febuxostat is a potent and selective inhibitor of xanthine oxidase, and thereby reduces the formation of xanthine and uric acid. No other enzymes involved in purine or pyrimidine metabolism are inhibited. In clinical trials, febuxostat at a daily dose of 80 mg or 120 mg was more effective than allopurinol at a standard 300 mg daily dose in lowering serum urate levels. The urate-lowering effect was comparable regardless of the pathogenic cause of hyperuricemia—overproduction or underexcretion. 

The bioavailability of azathioprine (80%) is superior to 6-MP (50%). After absorption azathioprine is rapidly converted by a nonenzymatic process to 6-MP. 6-Mercaptopurine subsequently undergoes a complex biotransformation via competing catabolic enzymes (xanthine oxidase and thiopurine methyltransferase) that produce inactive metabolites and anabolic pathways that produce active thioguanine nucleotides. Azathioprine and 6-MP have a serum half-life of less than 2 hours however, the... 

Clark, A. J. and Pratt, D. E. 1976. Xanthine oxidase activity in rat serum after administration of homogenized bovine cream preparation. Life Sci. 19, 887-892. 

McCarthy, R. D. and Long, C. A. 1976. Bovine milk intake and xanthine oxidase activity in blood serum. J. Dairy Sci. 59, 1059-1062. 

SOD activity was assessed using a Ransod kit (Randox Laboratories Ltd.) that quenches the rate of inhibition of 2-(4-iodophenyl)-3-(4-nitrophenol)-5-phenyltetrazolium (INT) reduction by the superoxide anion released after xanthine oxidation with xanthine oxidase. One unit of SOD causes a 50% inhibition rate and the activity was expressed as U mL of whole blood and reported to the normal range. In each case, appropriate control serum for quality control had been used. 

Recently, several studies have found that black tea and green tea offered protection against oxidative damage to red blood cells induced by a variety of inducers, such as hydrogen peroxide, primaquine, 2,2 -azo-fc (2-amidinopropane) dihydrochloride (AAPH), phenylhydrazine, copper-ascorbic acid, and the xanthine/xanthine oxidase system. Recently, we found that oral feeding of green tea leaves to rats resulted in enhanced superoxide dismutase (SOD) activity in serum and catalase activity in liver and an increased concentration of glutathione in the liver. ... 

Allopurinol is an inhibitor of xanthine oxidase, used to lower serum uric acid concentrations in the long-term treatment of gout and in the prevention of acute gout in people who are susceptible to hyperuricemia. Allopurinol is itself metabolized to its active metabolite, oxipurinol, by xanthine oxidase. 

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