Urinary Excretion of Uric Acid in Nonhuman Mammalian Species

Roch-Ramel, F; Peters, G

doi:10.1007/978-3-642-66867-8_9

Cited by 52 publications

(41 citation statements)

References 151 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…U rate oxidase (uricase) converts uric acid to 5-hydroxy isourate and H 2 O 2 , leading to the formation of allantoin (1). Mutation of the uricase gene during human evolution eliminated this source of H 2 O 2 and resulted in an average plasma urate concentration (PUA) of ∼0.3 mM (5 mg/dL), 5-to >20-fold higher than in most other mammals (2,3). Ames et al (4) proposed that, by scavenging free radicals, a higher PUA protects humans from cancer and other life-shortening disorders.…”

mentioning

confidence: 99%

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

Hershfield

Roberts²,

Ganson³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

A high plasma urate concentration (PUA), related to loss of urate oxidase in evolution, is postulated to protect humans from oxidative injury. This hypothesis has broad clinical relevance, but support rests largely on in vitro data and epidemiologic associations. Pegloticase therapy generates H 2 O 2 while depleting urate, offering an in vivo test of the antioxidant hypothesis. We show that erythrocytes can efficiently eliminate H 2 O 2 derived from urate oxidation to prevent cell injury in vitro; during therapy, disulfide-linked peroxiredoxin 2 dimer did not accumulate in red blood cells, indicating that their peroxidase capacity was not exceeded. To assess oxidative stress, we monitored F2-Isoprostanes (F2-IsoPs) and protein carbonyls (PC), products of arachidonic acid and protein oxidation, in plasma of 26 refractory gout patients receiving up to five infusions of pegloticase at 3-wk intervals. At baseline, PUA was markedly elevated in all patients, and plasma F2-IsoP concentration was elevated in most. Pegloticase infusion rapidly lowered mean PUA to ≤1 mg/dL in all patients, and PUA remained low in 16 of 21 patients who completed treatment. F2-IsoP levels did not correlate with PUA and did not increase during 15 wk of sustained urate depletion. There also was no significant change in the levels of plasma PC. Because refractory gout is associated with high oxidative stress in spite of high PUA, and profoundly depleting uric acid did not increase lipid or protein oxidation, we conclude that urate is not a major factor controlling oxidative stress in vivo.

show abstract

mentioning

confidence: 99%

Treating gout with pegloticase, a PEGylated urate oxidase, provides insight into the importance of uric acid as an antioxidant in vivo

Hershfield

Roberts²,

Ganson³

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

121

View full text Add to dashboard Cite

show abstract

“…Since S-8666 and furosemide are secreted by renal tubules, a circadian variation might also exist in tubular secretory function. Rats metabolize uric acid to allantoin in the liver with uricase (14). Therefore, when prop erties of uricosuric agents are evaluated using rats, the animals must be treated with the uri case inhibitor oxonate (15).…”

mentioning

confidence: 99%

Chronopharmacology of the New Uricosuric Diuretic S-8666 in Rats.

1991

View full text Add to dashboard Cite

A new loop diuretic with uricosuric activity, 6,7-dichloro-5-(N,N dimethylsulfamoyl)-2,3-dihydro-2-benzofuran carboxylic acid (S-8666), was given oral ly at 12:00 a.m. or 12:00 p.m. in rats. The diuretic of S-8666 and the urinary excre tions of the drug and its active metabolite S-8680 (N-demethyl S-8666) were greater at 12:00 a.m. than at 12:00 p.m.. Thus, the present study indicates that the diuretic effects of S-8666 varies with its administration time. Time-dependent variations in the amount of urinary excretions of S-8666 and S-8680 might be involved in the mecha nisms for this phenomenon.

show abstract

“…The transport of uric acid in the mammalian kidney involves glomerular filtration, tubular reabsorption and tubular secretion, though the relative importance of uric acid movement in each direction differs among species (7,8). The rat is a useful animal for evaluating drug effects on uric acid excretion because the net flux in the tubular excretory transport of uric acid is reabsorptive, although the fractional excretion of uric acid is obviously higher than that in man (9)(10)(11)(12)(13).…”

mentioning

confidence: 99%