Studies on the pathogenesis of uremia comparatie determinaions of glucuronic acid, indican, free and bound phenols in the serum, cerebrospinal fluid, and urine of renal diseases with and without uremia

Müting, D

doi:10.1016/0009-8981(65)90171-3

Cited by 66 publications

(40 citation statements)

References 3 publications

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“…This latter possibility was confirmed by the observation that indoxyl sulfate, which was strongly adsorbed to the gel, was able to inhibit the in vitro transport of urate and PiAH. This inhibitory effect of indoxyl sulfate occurred at concentrations comparable to those previously disclosed in uremic sera by Pasternack, Kuhlbick, and Tallgren (9) and by Miitting (10) as well as by the present study.…”

Section: 85±018supporting

confidence: 91%

“…The chemical substances tested were those that were eluted at the same position as the active fractions on the one hand and potassium indoxyl sulfate on the other. Potassium indoxyl sulfate, which is strongly adsorbed to the gel, was tested because it accumulates to very high concentrations in uremic serum (9,10). Uptake of potassium indoxyl sulfate by isolated renal tubules has also been evaluated with a 0.5 mM concentration of this compound in the medium.…”

Section: Methodsmentioning

confidence: 99%

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Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Boumendil-Podevin¹,

Podevin²,

Richet³

1975

J. Clin. Invest.

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A B S T R A C T Serum and urine from chronically uremic patients and normal individuals were subjected to gel filtration on Sephadex-G10. The effects of the eluted fractions on the uptake of urate and para-aminohippurate by isolated cortical tubules of rabbit kidney were investigated. According to the origin of the samples, one to three major groups of fractions inhibiting both urate and para-aminohippurate transport were disclosed. The first eluted group occurred for all the samples under study. The second one was demonstrated in both sera and urines from uremic patients but only in urines from normal individuals. The third one was exclusively detected in uremic sera and urines. Among all the compounds identified, only hippuric acid, eluted in the fractions of the second group, was capable of inhibiting the uptake of urate and para-aminohippurate in vitro. The concentration for which this inhibitory effect of hippuric acid occurred was in the range of that existing in uremic sera. Indoxyl sulfate, which accumulates to very high concentrations in uremic serum, could not be disclosed in the above-mentioned fractions. This is explained by the strong adsorption of this indole derivative to Sephadex gel. Potassium indoxyl sulfate, when tested in vitro at the concentration existing in uremic serum, substantially inhibited the uptake of both urate and para-aminohippurate. In normal subjects, ingestion of hippuric acid or potassium indoxyl sulfate significantly increased fractional urinary excretion of uric acid. On the basis of these results, it is suggested that progressive retention of hippuric acid, indoxyl sulfate, and other yet unidentified inhibitors may explain the gradual increase in urinary fractional excretion of urate This work was presented in part at a symposium on uremia sponsored by the International

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Section: 85±018supporting

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Boumendil-Podevin¹,

Podevin²,

Richet³

1975

J. Clin. Invest.

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“…data]. Muting [29] found m-and p-cresol and phenol in the serum of uremic patients, but whether this is a special case only in the uremic patient is not clearly described.…”

Section: Discussionmentioning

confidence: 99%

Pharmacokinetics of Wood Creosote: Glucuronic Acid and Sulfate Conjugation of Phenolic Compounds

1995

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Wood creosote, principally a mixture of non-, alkyl- and/or alkoxy-substituted phenolic compounds, was orally administered to adult male volunteers to determine its metabolites and pharmacokinetic parameters. After a 133-mg single dose, its major constituents (i.e. phenol 15 mg, guaiacol 32 mg, p-cresol 18 mg and creosol 24 mg) were found in peripheral venous blood and urine, mostly as glucuronic acid and, except for creosol, as sulfate conjugates. Low concentrations of un-conjugated phenols were also detected. The metabolites in the serum started to increase 15 min after the dose, and they reached their maximum concentrations 30 min after administration. The maximum concentrations of glucuronides were 0.18 ± 0.07,0.91 ± 0.38,0.33 ± 0.18 and 0.47 ± 0.23 mg/l; those of sulfates were 0.16 ± 0.06,0.22 ± 0.09,0.17 ± 0.07 and < 0.04 mg/l for phenol, guaiacol, p-cresol and creosol, respectively. The 24-hour urinary recoveries of the sum of each compound and its metabolites were 75 ± 35, 45 ± 36, 103 ± 51 and 74 ± 36%, in the above order. The presence of guaiacol glucuronide in blood and urine was directly verified by its isolation and structure analyses.

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“…Accumulation of indoxyl sulfate in the serum and cerebrospinal fluid has been considered to be a cause of symptoms such as cerebral dysfunction in uremic patients [5]. Indoxyl sulfate is synthesized in the liver from indole which is a tryptophan metabolite generated by the tryptophanases of intestinal bacteria such as E. coli and Klebsiella.…”

Section: Introductionmentioning

confidence: 99%

Suppressed Serum and Urine Levels of Indoxyl Sulfate by Oral Sorbent in Experimental Uremic Rats

et al. 1992

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In uremic patients, the serum concentration of indoxyl sulfate is markedly increased. To determine if oral sorbent (AST-120) suppresses the endogenous synthesis of indoxyl sulfate, it was administered to experimental uremic rats, and the serum concentration and urinary excretion of indoxyl sulfate were quantified by high-performance liquid chromatography. Oral sorbent decreased both the serum concentration and urinary excretion of indoxyl sulfate, suggesting that there was suppression of the endogenous synthesis of indoxyl sulfate by the oral sorbent. Oral sorbent did not decrease the serum concentration and urinary excretion of hippuric acid, but it did alleviate the deterioration of renal function in the experimental uremic rats.

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Studies on the pathogenesis of uremia comparatie determinaions of glucuronic acid, indican, free and bound phenols in the serum, cerebrospinal fluid, and urine of renal diseases with and without uremia

Cited by 66 publications

References 3 publications

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Uricosuric agents in uremic sera. Identification of indoxyl sulfata and hippuric acid.

Pharmacokinetics of Wood Creosote: Glucuronic Acid and Sulfate Conjugation of Phenolic Compounds

Suppressed Serum and Urine Levels of Indoxyl Sulfate by Oral Sorbent in Experimental Uremic Rats

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