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PubMed1975

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

Serum and urine from chronically uremic patients and normal individuals were subjected to gel filtration of 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 inhbiitory 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 observed in uremia. The present results may be viewed as an example of a mechanism in which retention of normally excreted end products is responsible for adaptation of tubular transport in uremic subjects.

Aminohippuric Acids↗
PubMed2002

Hippuric acid in urine: reference values.

OBJECTIVE: To establish reference values for hippuric acid (HA) excreted in the urine, and to evaluate the impact of age, gender, alcohol, and tobacco, on these levels in a population nonexposed to toluene. METHODS: Reference values for hippuric acid in urine were determined in 115 toluene nonexposed healthy volunteers, from Alfenas city, Southeastern Brazil. A questionnaire was applied to each volunteer and data on occupational and personal habits were collected. Biochemical and hematological analyses were used to confirm the volunteers' good health condition. Reference values were expressed in g HA/g urine creatinine, as mean +/- standard deviation (x +/- SD), median, 95% confidence interval (95%CI), 95th percentile, and upper reference value (URV, mean +2 SD). RESULTS: Reference values of hippuric acid in urine were: mean +/- standard deviation =0.18+/-0.10; median =0.15; 95% confidence interval =0.16+/-0.20; 95th percentile = 0.36 and upper reference value (URV, mean +2 SD) =0.38. Statistically significant differences in urinary HA (Wilcoxon - Mann/Whitney, p<0.05) were observed for different genders and age groups. Alcohol ingestion and smoking habit did not significantly affect the results. CONCLUSIONS: The reference values of hippuric acid in urine can be used in biomonitoring programs of workers occupationally exposed to toluene, especially in the southern region of the state of Minas Gerais. Age and gender may affect the HA reference values.

Adolescent↗
PubMed1980

Comparison of several methods for the measurement of urinary hippuric acid as an index of toluene exposure.

The levels of hippuric acid in the urine of people exposed to toluene vapour were measured by paper chromatography, direct colorimetry, high performance liquid chromatography and gas chromatography. The control was a similar group not exposed to toluene vapour. The values were analyzed statistically, conversion equations calculated, and the propriety of these equation discussed. Since the three chromatographic methods gave similar values, the measurement of urinary hippuric acid by these methods can be used as an index of toluene exposure. The colorimetric method gave higher levels the chromatographic methods, especially for the urine of people not exposed to toluene. This may have been due to glycine conjugates (other than hippuric acid) developing a similar color, resulting in elevated values for hippuric acid. This colorimetric method should be used with caution for biological evaluation of workers with low toluene exposure.

Air Pollutants, Occupational↗
PubMed1994

Dietary sources and background levels of hippuric acid in urine: comparison of Philippine and Japanese levels.

Levels of sodium benzoate in processed food from the Philippines and Japan were analyzed by high performance liquid chromatography. Results showed that of the 44 samples from the Philippines, 31 (70%) contained the compound. The samples with sodium benzoate included 19 juice, 6 softdrink and 6 soy sauce varieties. As for the Japanese products, only 8 (26%) out of 31 food items tested positive for sodium benzoate. The values of the compound in the Philippine samples ranged from 20 micrograms/ml to more than 2,000 micrograms/ml; the Japanese products showed a range of 50 to 200 micrograms/ml. Background urinary hippuric acid levels in 43 male Filipinos and 34 male Japanese with no occupational exposure to toluene were also measured using a high performance liquid chromatograph. Hippuric acid levels expressed as geometric means (SD) were 0.11 g/g creatinine (0.41) for the Filipino subjects and 0.09 g/g creatinine (0.39) for the Japanese subjects. No statistically significant difference in hippuric acid values in the 2 groups was noted. Possible explanations for the lack of any difference in background urinary hippuric acid levels between Filipino and Japanese subjects were discussed.

Benzoates↗
PubMed1983

A rapid hippurate hydrolysis test for the presumptive identification of group B streptococci.

A rapid test for the detection of sodium hippurate hydrolysis using sodium hippurate-impregnated strips was developed. This test made possible the detection of hippurate hydrolysis by Lancefield Group B beta-hemolytic streptococci within 10 min and required only a single colony for testing. All Lancefield Group B streptococci tested were positive for hippurate hydrolysis. All other strains of beta-hemolytic streptococci examined were negative with the exception of 2 strains of Group D beta-hemolytic streptococci.

Bacteriological Techniques↗
PubMed1986

Correlation of xylene exposure and methyl hippuric acid excretion in urine among paint industry workers.

Different calculations of methyl hippuric acid excretion in urine were correlated to the time-weighted average (TWA) of the xylene exposure of a complete workday for 40 paint industry workers exposed to 12 different solvents. The 8-h TWA xylene exposure varied between 0 and 865 (median 69) mg/m3. The amount of methyl hippuric acid excreted in about 24 h showed only a slightly higher linear correlation to the xylene exposure than the amount of methyl hippuric acid excreted per hour during the latter part of the workshift among the 37 subjects exposed to TWA xylene air concentrations of 0-200 mg/m3. It was concluded that the methyl hippuric acid excretion rate during the latter part of the workshift can be used for crude xylene exposure categorizations.

Adult↗
PubMed2002

High levels of hippuric acid in the urine of Thai press workers.

Toluene is an important toxic volatile agent found in many modern industrial processes. Toluene exposure is of particular concern because of the ongoing exposure of thousands of workers in industrial plants and recent research has indicated that toluene/exposure can result in chronic toxicity. The monitoring and control of toluene exposure among at-risk workers is necessary. Urine hippuric acid determination is a helpful test monitoring groups of at-risk workers. In this study, urine samples were obtained from 20 control subjects and 48 press workers from a factory in Bangkok. Each subject gave a specimen of urine; each specimen was analyzed for hippuric acid level by the Ohmori method. The average urine hippuric acid level in the control group was 0.23 +/- 0.15 mg/gCr (range = 0.05 - 0.58 mg/gCr) while that of the experimental group was 0.37 +/- 0.37 mg/gCr (range = 0.06 - 0.18 mg/gCr). A significant higher urine hippuric acid level among the press workers was found (p = 0.03). Based on this study, the prevention of exposure to toluene among high-risk workers is recommended.

Case-Control Studies↗
PubMed1992

Benzoyl-CoA ligase activity in the liver and kidney cortex of weanling guinea pigs treated with various inducers: relationship with hippurate synthesis and carnitine levels.

Recent reports have indicated that guinea pig may be a better model for the study of benzoate conjugation in humans because of the presence of a salicylate-activating ligase. We gave intraperitoneal injections of sodium benzoate, sodium salicylate, sodium methylprednisolone and sodium phenobarbital for 4 consecutive days to groups of weanling guinea pigs before sacrifice. A measurement of benzoyl-CoA ligase activity and in vitro hippurate synthesis was done in liver and kidney cortex homogenates from each treated group at 21 days of age, as compared to an untreated (saline) 21-day control group. The results indicate that benzoyl-CoA ligase in guinea pigs is affected by phenobarbital (liver and kidney; p < 0.05-0.01) and methylprednisolone (liver; p < 0.01). Liver hippurate synthesis was also significantly induced by phenobarbital (p < 0.01). Both these treated groups also had reduced levels of free carnitine in plasma taken from 21-day-old guinea pigs as compared to the untreated control. Sodium benzoate did not have any effect on benzoyl-CoA ligase activity or on in vitro hippurate synthesis. However, sodium salicylate did show some effect on the induction of liver and kidney benzoyl-CoA ligase (not significant) and liver (p < 0.05) and kidney hippurate synthesis. It is important that studies on the guinea pig model be extended for application to children receiving therapy of benzoate and other aromatic acids like p-aminobenzoate or salicylate.

Animals↗
PubMed1991

Serum hippurate and its excretion in conservatively treated and dialysed patients with chronic renal failure.

54 healthy volunteers or patients with normal kidney and liver function, 17 patients with decreased kidney function and 12 dialysed patients were evaluated for their serum hippurate accumulation and kidney excretion. It was found that there was an inverse relationship between serum hippurate and the clearance of endogenous creatinine (CCr) and a free relationship between fractional excretion of hippurate and CCr. The excretory capacity in residual nephrons was increased. This was caused by the greater glomerular filtration load which increased up to 25 times and tubular secretion which increased 7 times in dialysed patients. The relative contribution of glomerular filtration to hippurate excretion rose from about 20% in controls to almost 50% in dialysed patients. True kidney adaptation was localized in the organic anion transport system of proximal tubules.

Hippurates↗
PubMed1990

Effect of hippurate on tissue fatty acid metabolism.

The authors studied 1-14C-palmitate metabolism in rat muscle, renal cortex and liver incubated with synthetic hippurate in vitro (1 mmol/l). a) Hippurate did not affect 1-14C-palmitate uptake and utilization in the muscle (hemidiaphragm). b) In the renal cortex it stimulated only the incorporation into total lipids and from the individual lipid fractions into mono- and diglycerides and free fatty acids (FFA). c) In the liver it stimulated the uptake, oxidation to 14CO2 and incorporation into total lipids and, out of the individual lipid fractions, into phospholipids, triacylglycerols and free fatty acids. d) Hippurate already had a significant effect in the concentration of 0.5 mmol/l, i.e. during the development of the disturbance and not just as a supplementary factor in advanced renal insufficiency. It is concluded that, by interfering with fatty acid metabolism, the hippurate present in the serum of patients with renal insufficiency plays an active role in the development of dyslipoproteinaemia in such patients.

Animals↗
PubMed1989

Measurement of apolipoprotein B synthesis in perfused rat liver using stable isotopes: [15N]hippurate as a measure of the intracellular [15N]glycine precursor enrichment.

Rat livers were perfused by the nonrecirculating technique with medium containing [15N]glycine and sodium benzoate. At various times, the isotopic enrichment of hepatic free glycine, hepatic glycyl-tRNA, and perfusate hippurate was measured by GLC-MS. After 60 min, these parameters had reached approximately maximal values. At 90 min, the perfusate hippurate had a 30% greater enrichment of 15N than the intracellular glycine or glycyl-tRNA. Hippurate enrichment was half that of the medium glycine. The rat livers secreted apolipoprotein B (B-100 plus B-48) at a rate of 22 micrograms/g per h. From the 15N enrichment and the secretion rate, an intrahepatic pool size of 86 micrograms/g of apoB was calculated. From the minimal intracellular transit time of 30 min, an apoB fractional synthetic rate (FSR) of 2 pools/h was indicated, whereas the FSR estimated from the 15N-enrichment was 0.26/h. A possible explanation for the discrepancy is that apoB may recycle within the hepatocyte. On the basis of the present experiments, when hippurate enrichment is used as a measure of the enrichment of intrahepatic glycine in in vivo studies with 15N-labeled glycine, a correction should be applied, under normal metabolic circumstances, of approximately 20-30%.

Animals↗
PubMed1979

[The excretion of hippuric acid and ascorbic acid in the urine of liver-damaged rats (author's transl].

The authors investigated the effects of the administration of thioacetamide, carbon tetrachloride and aminophenazone on the excretion of ascorbic acid and hippuric acid in adult male and female Wistar rats. After a single application of thioacetamide and aminophenazone, the ascorbic acid content in the urine showed a dose-dependent increase, whereas that in the liver had decreased. This increase in the urinary ascorbic acid might be due to a release of stored ascorbic acid from the liver cells. When thioacetamide was given for a prolonged period, the ascorbic acid content in the urine increased at the beginning; later one, at the end of three weeks, it was slightly inferior to the control value. Both single and repeated applications of thioacetamide led to a decrease in the excretion of hippuric acid in the urine, which is attributed to an impairment of the mitochondrial hippuric acid synthesis. Long-term treatment with aminophenazone resulted in an increase of ascorbic acid in the urine, which is indicative of an induction effect, whereas the ascorbic acid content in the liver remained unchanged. There was no effect on the excretion of hippuric acid. In regard to their use in the toxicological evaluation of drugs, these two metabolic effects offer no decisive advantage over current liver function tests.

Aminopyrine↗
PubMed1975

[Transport of 131J-iodo-o-hippurate and 22Na out of the retroretinal space in experimental non rhegmatogenous detachment of the retina (author's transl)].

A model of an experimental arhegmatogenous retinal detachment is presented, to allow the measurement of the transport of radioactive labeled substances out of the subretinal space. Experiments were performed on 19 male cats. 131I-iodo-o-hippurate and 22Na were used as test substances. There was no significant difference between the rate of disappearance of 131I-hippurate if injected retroretinally or intravitreally. The rate of disappearance of 131I-hippurate could be slowed down by intravenous infusion of penicillin-G. The rate of disappearance of 22Na following retroretinal injection is not only slower than the rate of disappearance of 22Na injected intravitreally, but significantly slower than the rate of disappearance of 131I-hippurate. For graphic analysis ("curve peeling") of the terms embodied in the curves, more densly situated points of measurements will be necessary. Then the experimental model will serve well to analyze the components influencing the transport of labeled sodium out of the subretinal space.

Animals↗
PubMed1990

[Mean elimination time of the impulse radiotracer (131I-hippurate) as a marker of renal function].

A possibility of assessment of renal excretory function using mean time of the impulse tracer (131I-hippurate) dose elimination has been shown on the basis of theoretical analysis of hippurate kinetics. Such an index was calculated during classic hippurate renography from time/activity curve over precordium. Other traces and different regions of monitoring might also be employed. The mean time of tracer elimination obtained in this manner only indirectly reflects the hippurate clearance, yet can be easily achieved. Moreover, this entity is not influenced by errors related to quantitative measurements of radioactivity and to hypothetical assumptions, which are common for more sophisticated isotope clearance methods. The enlisted characteristics seem to predispose the proposed method of renal function evaluation for application in screening isotope tests.

Humans↗
PubMed1994

Application of micellar electrokinetic capillary chromatography for monitoring of hippuric and methylhippuric acid in human urine.

The factors affecting micellar electrokinetic capillary chromatographic separation of hippuric and o-, m-, p-methylhippuric acid were investigated by changing the species of micelles, and adding urea to the micellar solution. The analysis of hippurates in human urine is demonstrated under optimum conditions using 20 mM phosphate buffer (pH 8.0) containing 100 mM dodecyltrimethylammonium bromide and 4 M urea at -22 kV applied voltage. This method proved suitable for the screening of hippurates in human urine following occupational exposure to toluene and xylene.

Buffers↗
PubMed1985

Intracellular localization and some properties of the system in guinea pig liver responsible for the aromatization of cyclohexanecarboxylic acid to hippuric acid.

The conversion of cyclohexanecarboxylic acid to hippuric acid in subcellular fractions from guinea pig liver was studied using a gas chromatographic-mass spectrometric method employing selected ion monitoring. Comparison of the activities of the cyclohexanecarboxylic acid to hippuric acid converting system (CHC-system) and marker enzymes in the various subcellular fractions showed that the CHC-system is localized exclusively in the mitochondria. No contribution to the total activity of the system was made by microsomal enzymes. The activity of the CHC-system in whole liver homogenate and in isolated mitochondria was similar when the latter were supplemented with ATP, alpha-ketoglutaric acid, glycine, ethylenediaminetetraacetate, PO4(3-) and Mg2+. The formation of hippuric acid in these mitochondrial preparations was linear with respect to time over a period of at least 60 min. Studies designed to optimize the incubation conditions showed that the activity of the CHC-system was reduced by PO4(3-) concentrations greater than approximately 70 mM. Conversely, both ATP and alpha-ketoglutaric acid stimulated the system. It is possible that two different types of acyl-CoA synthetases, one which is ATP-specific and one which is GTP-specific, may operate in the activation of cyclohexanecarboxylic acid.

Adenosine Triphosphate↗
PubMed1983

Urinary excretion of hippuric acid and o-cresol after laboratory exposure of humans to toluene.

The urinary excretion of hippuric acid and o-cresol was studied after respiratory exposure of human volunteers to approximately 80 ppm (306 mg/m3 +/- SD 13) of toluene for 2 h under different work loads (0, 50, 100, 150 W, respectively, during 30-min periods). The diet before and after exposure varied. An isotachophoresis method for the determination of hippuric acid is described. The correlation between the total urinary excretion, excretion rate and concentration of hippuric acid, and the respiratory uptake of toluene was poor or non-existing. The same was true for the excretion of o-cresol, which 4 h after exposure was concluded amounted to 0.03-0.26% of the toluene uptake. Thus, after a short-time exposure neither metabolite proved to be a reliable measure of individual toluene uptake at varying workloads or food intake in combination with low exposure levels.

Adult↗
PubMed1989

Excretion of hippuric acid during sodium benzoate therapy in patients with hyperglycinaemia or hyperammonaemia.

In patients with non-ketotic hyperglycinaemia and two patients with urea cycle disorders treated with varying doses of sodium benzoate there was linear correlation between intake of benzoate and excretion of hippurate. Patients with non-ketotic hyperglycinaemia excreted significantly more benzoate in the form of hippurate than patients with urea cycle disorders (74 +/- 7.0 vs 41 +/- 3.6%). The plasma concentration of glycine decreased following benzoate treatment only in the patients with non-ketotic hyperglycinaemia. The observed difference between the two groups in the excretion of hippurate seems to support the concept that glycine availability may be limiting in benzoate therapy for some patients.

Amino Acid Metabolism, Inborn Errors↗