Uricase Inhibition in the Rat by s-Triazines: An Animal Model for Hyperuricemia and Hyperuricosuria

Johnson, Willard J.; Stavrić, B.; Chartrand, A.

doi:10.3181/00379727-131-33791

Cited by 73 publications

(26 citation statements)

References 2 publications

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“…[12] and trichloropurine (50 mg/kg s.c.) [ 131, both inhibitors of urate oxidase; allopurinol(150 mg/kg s.c.), an inhibitor of xanthine oxidase [14,15] …”

Section: Methodsmentioning

confidence: 99%

In vivo cooperation between hepatic catalase and superoxide dismutase demonstrated by diethyldithiocarbamate

Geerts

Roels

1982

FEBS Letters

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“…[12] and trichloropurine (50 mg/kg s.c.) [ 131, both inhibitors of urate oxidase; allopurinol(150 mg/kg s.c.), an inhibitor of xanthine oxidase [14,15] …”

Section: Methodsmentioning

confidence: 99%

In vivo cooperation between hepatic catalase and superoxide dismutase demonstrated by diethyldithiocarbamate

Geerts

Roels

1982

FEBS Letters

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“…according to Johnson et al (2). The first administration of the agent progressively increased plasma uric acid and urine volume, while the second treatment after a 2-hr interval retained the high levels of plasma uric acid and urine volume for 2 hr or more.…”

Section: Methodsmentioning

confidence: 99%

“…The rat is such an animal because it shows a reabsorptive net flux of uric acid in the renal tubules, though the animal handles uric acid by both hepatic metabolism and renal excretion. On the other hand, useful inhibitors of urate oxidase have already been developed to create the disease model of hyperuricemia (2)(3)(4), but the inhibitor-treated animals have not been utilized enough for evaluating uricosuric agents. A practical procedure for evaluating the drugs with potassium oxonate treated rats is reported here.…”

mentioning

confidence: 99%

Effects of uricosuric drugs and diuretics on uric acid excretion in oxonate-treated rats.

Yonetani

Iwaki

1983

Jpn.J.Pharmacol

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Abstract-A practical procedure for evaluating uricosuric agents was demonstrated using clearance experiments with potassium oxonate-treated rats. The fractional excretion value of uric acid showed a reabsorptive net flux of uric acid in the renal tubules of the animal, though the value was obviously higher than those of primates such as men, chimpanzees and cebus monkeys. However, the rats responded well to uricosuric drugs and diuretics. Probenecid and uricosuric diuretics such as tienilic acid induced hyper uricosuria due to the increase of fractional excretion of uric acid and/or the increase of the filtered amount of uric acid with the rise of plasma uric acid. On the other hand, furosemide had no effect on uric acid excretion at a low dose with moderate diuresis, while a higher dose decreased the fractional excretion of uric acid with elevation of plasma uric acid. Benzothiazides were also uricosuric at the lower doses, but the high dose, as in the case of the so-called uricosuric drugs, had no effect on the uric acid excretion and plasma uric acid level. Thus, oxonate-treated rats were useful for evaluating drug effects on uric acid excretion.Because of species differences in the metabolism and excretion of uric acid, animal experiments have contributed little to the evaluation of drug activities on the renal handling of uric acid, except for those using primates such as chimpanzees and cebus monkeys. The urinary excretion of uric acid, however, has been well studied with various nonhuman mammalia in order to find useful animals for the evaluation, resulting in some successful examples (1). The rat is such an animal because it shows a reabsorptive net flux of uric acid in the renal tubules, though the animal handles uric acid by both hepatic metabolism and renal excretion. On the other hand, useful inhibitors of urate oxidase have already been developed to create the disease model of hyperuricemia (2-4), but the inhibitor-treated animals have not been utilized enough for evaluating uricosuric agents. A practical procedure for evaluating the drugs with potassium oxonate treated rats is reported here. Materials and MethodsTen-week-old male Slc-Wistar rats were used. To determine uric acid and inulin clearance, the animals were given potassium oxonate, 250 mg/kg i.p., and then the right femoral artery, left femoral vein and urinary bladder were cannulated for blood collection, infusion and urine collection, respectively, under anesthesia with sodium pentobarbital, 50 mg/kg i.p., within 2 hr after the adminis tration of oxonate. The same dose of oxonate was given again just 2 hr after the first administration, and then 60% urethane, 2 ml/kg, and 15% inulin, 4 ml/kg, were administered subcutaneously. The animals were then infused with 4% mannitol-1.5% inulin-0.9% sodium chloride solution at the flow rate of 0.1 ml/min on a hot plate at

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“…[11,14]. After intravenous bolus injection of [ The radioactivity was mainly eliminated via renal excretion in both rats.…”

Section: Dipea: Nn-diisopropylethylaminementioning

confidence: 99%

“…In rodents, uric acid is the product of purine metabolism, and is subsequently degraded by the hepatic enzyme uricase into a water-soluble product (allantoin) [11]. In humans, uric acid is the end product of purine metabolism due to the lack of uricase [12,13].…”

Section: Dipea: Nn-diisopropylethylaminementioning

confidence: 99%

Synthesis of [11C]uric acid, using [11C]phosgene, as a possible biomarker in PET imaging for diagnosis of gout

Yashio¹,

Katayama²,

Takashima³

et al. 2012

Bioorganic & Medicinal Chemistry Letters

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Uricase Inhibition in the Rat by s-Triazines: An Animal Model for Hyperuricemia and Hyperuricosuria

Cited by 73 publications

References 2 publications

In vivo cooperation between hepatic catalase and superoxide dismutase demonstrated by diethyldithiocarbamate

In vivo cooperation between hepatic catalase and superoxide dismutase demonstrated by diethyldithiocarbamate

Effects of uricosuric drugs and diuretics on uric acid excretion in oxonate-treated rats.

Synthesis of [11C]uric acid, using [11C]phosgene, as a possible biomarker in PET imaging for diagnosis of gout

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