A spectrofluorometric method for determining plasma allantoin based on the glyoxylate reductase reaction

Abstract-Effects of antihypertensive and uricosuric drugs were studied on the plasma and urinary levels of uric acid in oxonate-treated rats. We made use of animals with a catheterized aorta to successively collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with potassium oxonate.The plasma uric acid level of the oxonate-treated rats was increased even with a single administration of diuretic chlorothiazides, furosemide, diazoxide and also uricosuric drugs such as tienilic acid and probenecid.On the other hand, a wellmaintained plasma uric acid level was also produced by exogenously administered uric acid in rats which had been given allopurinol and potassium oxonate.Diazoxide, tienilic acid and probenecid increased the plasma uric acid, while diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration to rats treated with allopurinol, oxonate and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading test with rats treated with allopurinol and oxonate. These effects also appeared as changes in the urine-excreted uric acid. Thus, the oxonate-treated rats demonstrated an acutely induced hyperuricemia not only with certain antihypertensives, but also with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.Since selective inhibitors of urate oxidase were reported by Fridovich (1) and Iwata et al.(2), the utility of inhibitor-treated animals has enabled a better understanding of various problems related to hyperuricemia (3).However, it has not been clarified whether such an approach is feasible for predicting the hyperuricemic or uricosuric effects of drugs; in particular, problems arising from species differences in the renal functions for uric acid excretion should be further investigated.Hyperuricemia is sometimes reported to be an undesirable side effect of some anti hypertensives (4-8), and a number of agents have been practically utilized as uricosuric drugs.However, the characterization of these drugs has been mainly developed in the clinical field, and therefore a useful model for evaluating characteristics in animal studies has long been awaited. The present study was undertaken to evaluate the utility of potassium oxonate-treated rats as models for such a purpose. Acutely induced hyperuricemia was demonstrated by some antihypertensive and uricosuric drugs. MATERIALS AND METHODS Animals:Nine-week-old male Wistar strain rats were maintained on a solid diet CA-1 (Japan CLEA Co., Tokyo) and tap water ad libitum. Experiments were done using rats

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“…Plasma uric acid and allantoin were estimated basically according to the methods of Sumi et al (9,10).…”

Section: Animalsmentioning

confidence: 99%

Hyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats.

1980

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“…The concentrations of metabolites were measured by fluorimetric techniques, essentially based on the spectrophotometric methods developed for ammonia [2], urea [3], alanine [4], glutamine and glutamate [5] and allantoin [6). The fluorescence of the NADH gen erated was measured at 340 nm for the excitation wavelength and 450 nm for the emission wavelength.…”

Section: Methodsmentioning

confidence: 99%

Maternal-Fetal Relationship in Ammonia Metabolism during Late Gestation in the Rat

Martín‐Barrientos²,

Jm³

1988

Neonatology

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The concentrations of the major metabolites for nitrogen excretion and/or transport in maternal and fetal blood and amniotic fluid during the last 2 days of gestation were investigated. Alanine, glutamine, ammonia and allantoin accumulated in amniotic fluid during late gestation. Urea concentrations increased in amniotic fluid though only during the last day of gestation, suggesting that urea is taken up by the mother through the amniotic membranes. Glutamate did not accumulate in amniotic fluid during late gestation although high concentrations of it were found in fetal blood in the same circumstances, suggesting the occurrence of a mechanism for preventing fetal glutamate disposal.

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“…Uric acid and allantoin were determined basically according to the methods of Sumi et al (4)(5)(6), inulin was measured by the method of Vurek and Pegram (7), and urinary protein and occult blood were assessed using clinical test paper (LABSTIX-II, Miles Sankyo Co.). Data are shown as the mean value and standard error; the difference from the control level or the level before dosing was evaluated using Tukey's method after one-way analysis of variance.…”

Section: Methodsmentioning

confidence: 99%

Decreasing effect of allantoxanamide, a hyperuricemic agent on renal functions in rats.

1987

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Abstract-Both potassium oxonate and allantoxanamide have been reported as useful reagents for inhibiting urate oxidase, with the hyperuricemic effect of al lantoxanamide being longer-lasting than that of oxonate in rats. The present study was done to evaluate the utility of allantoxanamide for investigating problems concerning hyperuricemia using rats. A single intraperitoneal administration of 1 50 mg/kg allantoxanamide elevated the plasma uric acid level progressively during the experiment for 6 hr, resulting in a much higher level than that maintained by means of repeated dosing with 250 mg/kg potassium oxonate, i.p., at 2-hr intervals. Such a severe and long-lasting hyperuricemia caused by allantoxanamide was due to decreased renal function of uric acid excretion according to its nephrotoxicity in addition to the inhibition of urate oxidase like that by oxonate. Thus, we concluded that allantoxanamide might be a useful reagent for investigating the causes of hyperuricemia with renal failure, but was not a practical agent like oxonate in order to evaluate the response to uricosuric agents.

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A spectrofluorometric method for determining plasma allantoin based on the glyoxylate reductase reaction

Cited by 18 publications

References 3 publications

Hyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats.

Hyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats.

Maternal-Fetal Relationship in Ammonia Metabolism during Late Gestation in the Rat

Decreasing effect of allantoxanamide, a hyperuricemic agent on renal functions in rats.

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