Urinary Excretion Of D-glucaric Acid Research Articles

The effect of repeated administration of diftalone on enzyme induction.

Plasma concentrations of diftalone have been examined in normal volunteers after a single dose (500 mg) and after 500 mg doses given twice daily for one week. An increase in post dosing urinary excretion of D-glucaric acid showed a correlation with the ratio of calculated to observed areas under the plasma concentration, time curve following the final dose in the multiple dosing studies, indicating that hepatic microsomal enzymes are induced after repeated administration of the drug. Single dose studies in the presence of aluminium hydroxide and sodium bicarbonate showed that the antacids had no significant effect on the absorption of diftalone.

Effect of Antiepileptic Drugs on the Urinary Excretion of Porphyrins in Non-porphyric Subjects

The action of some anticonvulsant drugs as the causal agents of attacks of acute porphyria has been widely documented in the literature. However, little attention has been paid to the effect of these drugs on the urinary excretion of porphyrins in non-porphyric subjects. In a sample of 82 epileptic patients treated with phenobarbital (n = 54), phenytoin (n = 64), carbamazepine (n = 33), and valproate (n = 8), the daily doses were expressed according to a drug score that would reflect the capacity of these drugs as enzymatic inducers when administered in polytherapy. A significantly increased urinary excretion of D-glucaric acid (DGA) and porphyrins was found in this group of patients (P<0.001), with coproporphyrin being the major fraction in all cases (>60%). Urinary DGA had a highly significant correlation with the drug score (r = 0.783, P<0.001); however, no significant correlations were found between the urinary porphyrins and DGA (r = 0.005) or the drug score (r = 0.053). Neither was any significant relationship found between the urinary porphyrins and the serum activity of 5′-nucleotidase (r = 0.066) or the presence of a cholestasis objectivized through the presence of the isoform of γ-glutamyltransferase with β-globulins electrophoretic mobility. However, in a group of 10 patients a significant correlation was found between the urinary excretion of porphyrins and β-N-acetylhexosaminidase (r = 0.790, P<0.01). Therefore, it does not appear that the liver enzyme induction, or even a subclinical cholestasis, produced by the antiepileptic drugs administered to these patients may serve to explain the increase in the urinary excretion of porphyrins. A possible renal origin is proposed for the increase of urinary porphyrins in these cases.

Carbamazepine regulates intestinal P-glycoprotein and multidrug resistance protein MRP2 and influences disposition of talinolol in humans.

The antiepileptic drug carbamazepine is known to be an inducer of cytochrome P450 (CYP) 3A4 after binding to the nuclear pregnane X receptor. To evaluate whether it also regulates the multidrug transporter proteins P-glycoprotein (P-gp) and multidrug resistance protein MRP2 in humans, duodenal expression of multidrug resistance gene MDR1 messenger ribonucleic acid (mRNA) and MRP2 mRNA, content of P-gp and MRP2, and disposition of the nonmetabolized P-gp substrate talinolol after intravenous (30 mg) and long-term oral administration (100 mg for 19 days) were assessed in 7 healthy subjects (age, 23-35 years; body weight, 64-93 kg) before and after comedication of carbamazepine (600 mg for 14-18 days). Carbamazepine medication was associated with increased urinary excretion of D-glucaric acid and induction of carbamazepine elimination. Creatinine clearance was not affected. Duodenal expression of both MDR1 mRNA and MRP2 mRNA and the MPR2 protein was significantly induced, whereas the P-gp content was not affected. MDR1 mRNA expression and MPR2 mRNA expression were correlated ( r = 0.873, P <.001). After carbamazepine, metabolic clearance of intravenous talinolol was significantly increased. Residual clearance was significantly decreased in dependence on MDR1 mRNA expression ( r = -0.647, P =.012) and MRP2 mRNA expression ( r = -0.613, P =.020). Oral absorption of talinolol was significantly lower after carbamazepine comedication (53.2% +/- 15.5% versus 62.1% +/- 13.0%, P =.018), and renal clearance and metabolic clearance were significantly increased, correlated in each case with MDR1 mRNA ( r = 0.612, P =.020, and r = 0.554, P =.040, respectively) and MRP2 mRNA ( r = 0.596, P =.025, and r = 0.565, P =.035, respectively). Aside from induction of CYP3A4, carbamazepine acts as an inducer of intestinal MDR1 mRNA, MRP2 mRNA, and MRP2 protein content.

Assessment of copper status in epileptic patients treated with anticonvulsant drugs by measuring the specific oxidase activity of ceruloplasmin

Significant increases in serum levels and decreases in hair copper levels have been previously described in epileptic patients treated with anticonvulsant drugs. A condition not directly related to copper nutriture, such as chronic treatment with these drugs, could increase the serum concentrations of copper and ceruloplasmin and would mask a possible copper deficiency produced by drug-increased biliary copper excretion. Serum immunoreactive ceruloplasmin concentration and its oxidase activity were determined in 90 adult epileptic patients treated with phenobarbital ( n=60), phenytoin ( n=70), carbamazepine ( n=33) and valproic acid ( n=8). The levels of ceruloplasmin and oxidase activity were significantly higher ( P<0.001) than in an age and gender-matched control group ( n=49). The significant correlations ( P<0.01) between ceruloplasmin and the urinary excretion of d-glucaric acid, serum gamma-glutamyltransferase (GGT) and drug score in the patients group, would suggest that phenobarbital-type enzyme-inducing agents may increase the hepatic synthesis of ceruloplasmin. In 11 patients with a β-globulin migrating GGT isoform (GGT3), a sensitive marker of cholestasis, the levels of ceruloplasmin, oxidase activity and total GGT activity were significantly higher ( P<0.05) than in the group of 79 patients without the GGT3 isoform; consequently, in some cases a drug-induced cholestasis may also contribute to the increase of serum copper and ceruloplasmin. The values obtained for the specific oxidase activity of ceruloplasmin (activity per unit mass of enzyme protein) suggest that in the most of the cases, chronic administration of phenobarbital, phenytoin, carbamazepine or valproic acid, does not produce marginal or moderate copper deficiency.

Relationship between PCBs in blood and d-glucaric acid in urine

The polychlorinated biphenyls (PCBs) have been demonstrated to be inducers of hepatic microsomal enzymes and some of their effects such as hormonal imbalance, and alteration of lipid and porphyrin metabolism could be ascribed to this mechanism. For this reason, the urinary excretion of d-glucaric acid (DGA), an indirect indicator of enzymatic induction, was suggested as a biological marker of effect following exposure to PCBs. The aim of the present study was to investigate whether any inductive effects resulting from exposure to these compounds through ingestion of contaminated food could be detected early by measuring urinary DGA (U-DGA). U-DGA was measured in 73 subjects exposed to PCBs due to ingestion of PCB-contaminated food and levels ranged from 1.7 to 12.4 mmol/mol creatinine, with a mean value of 5.96 mmol/mol creatinine. These values were higher than those usually found in the general population. Sex and smoking habits did not affect U-DGA excretion, while age and alcohol intake were significantly correlated with U-DGA excretion, a finding in agreement with the results of other investigations. Neither total PCB blood concentration nor PCB chlorine content was significantly correlated with U-DGA excretion, and only the PCB 138 congener was weakly correlated with U-DGA levels. The results indicate that, for exposure to PCB resulting in blood concentrations up to 394 μg/l, no statistically significant effect of these persistent organochlorine compounds on human enzyme induction could be demonstrated, as measured by DGA urinary excretion.

Occupational exposure to anaesthetic gases and urinary excretion of D-glucaric acid

In order to ascertain whether the urinary excretion of D-glucaric acid (DGA) might be a suitable biomarker of effect in monitoring workers exposed to anaesthetic gases, we measured DGA before and after an operating session (and, in some workers, before and after a 2-week vacation) in 229 workers of surgical units and in 229 controls. In the former, we also measured urinary levels of nitrous oxide (N2O) and isofiurane after at least 4 h of exposure. For all subjects, information on age, smoking habits, daily intake of alcohol, coffee, and drugs, history of liver or kidney disease was collected. Study subjects were ranked according to: exposure (class 0: subjects not exposed; class 1: N2

Environmental and Biological Monitoring of Styrene Exposure: Urinary Excretion of D‐Glucaric Acid Compared with Exposure Indices

Environmental and Biological Monitoring of Styrene Exposure: Urinary Excretion of D‐Glucaric Acid Compared with Exposure Indices: M.L. Scapellato, et al. Istituto di Medicina del Lavoro, University degli Studi di Padova—Styrene, oxidized by liver microsomal enzymes, can determine a liver enzyme induction. Urinary excretion of D‐glucaric acid (DGA), which is believed to estimate this effect, was measured in 27 workers exposed to styrene in a fiberglass plant and in 27 control subjects in order to make a comparison with environmental and biological exposure indices. In exposed workers, airborne concentrations (8‐h TWA) of styrene varied between 9 and 415 mg/m3, with styrene metabolites [sum of mandelic acid (MA) + phenylglyoxylic acid (PGA)] ranging from 93 to 2130 mg/g Cr in endshift urine samples collected on a Thursday, and from 45 to 792 mg/g Cr in samples taken before work the following morning. The correlation coefficient (r) between 8‐h TWAs and sum of urinary metabolites MA + PGA was 0.92 (y=4.06x‐36.05; p&lt;0.001) for Thursday endshift (ES) samples, and 0.84 (y=1.46x + 46.82; p&lt;0.001) for Friday morning samples (beginning of shift: BS). Urinary excretion of MA correlated better with exposure than that of PGA (MA: ES r=0.91; BS r=0.86. PGA: ES r=0.80; BS r=0.76). ES and BS levels of DGA in exposed subjects (equal to 4.41 ± 1.57 and 4.01 ±1.18 mmol/mol Cr respectively) were both significantly higher than the 2.93 ± 0.88 observed in 27 control subjects (Mann‐Whitney test; p&lt;0.001). No significant correlation was found between individual exposure to styrene evaluated by the environmental concentration or by urinary metabolites and urinary excretion of DGA. Furthermore, both ES and BS urinary DGA levels increased across three classes of styrene exposure (&lt;100, 101‐200, and &gt;200 mg/m3, respectively, including 10, 7 and 10 workers). The DGA difference between the most exposed and the not exposed subjects was significant (ES‐DGA: z=4.03 and p &lt;0.05; BS‐DGA: z=3.16 and p&lt;0.05; Kruskall‐Wallis test), but individual pairwise comparisons among all other groups were not. In spite of the above results, no significant correlation was found between individual exposure to styrene and urinary excretion of DGA, so that this biomarker cannot be used to monitor the exposure effects on an individual basis.

In vivo studies on genotoxicity of pure and commercial linuron

The ureic herbicide linuron [3-(3,4-dichlorophenyl)-1-methoxy-1-methylurea] (CAS 330-55-2) was investigated for genotoxicity in a series of in vivo experiments. Since human exposure to herbicides is not only to the active principles, but also to all the chemicals present in the commercial formulation, we tested both pure and commercial linuron. Groups of rats were treated with gavage containing different doses of the herbicide (pure compound or commercial formulation) for 14 days. The doses were 150, 300 and 450 mg/kg b.wt. for the pure compound and 315.8, 631.6 and 947.4 mg/kg b.wt. for the commercial formulation (47.5% of linuron). Faeces and urine were collected at regular intervals. Urine specimens were analysed for their mutagenic metabolites, thioethers and d-glucaric acid content. Faeces extracts were tested for mutagenicity. Linuron's ability to cause DNA damage and cytogenetic effects was also investigated after treating groups of rats once with different doses of pure or commercial linuron. DNA single-strand breaks were assessed in rat liver using the alkaline elution technique and the single-cell microgel electrophoresis assay (SCGE: `comet' assay), and in rat testes cells with the SCGE assay. Micronuclei induction was analysed in rat bone marrow erythrocytes. Results obtained were mainly negative when the excretion of mutagenic metabolites in urine and faeces of animals treated with the pure compound or with the linuron-based commercial formulation were monitored, whereas an increase in the urinary excretion of thioethers and d-glucaric acid was observed in rats treated with the commercial formulation. No increase in the frequency of micronucleated polychromatic erythrocytes was observed in the treated animals. However, linuron affected the viability of hepatocytes isolated from animals treated with higher doses. This cytotoxicity was accompanied by the induction of DNA single-strand breaks in the liver, as seen by the alkaline elution assay. The potential of pure linuron to induce in vivo DNA damage was confirmed with the microgel electrophoresis technique (`comet' assay). Cytotoxicity was also seen in rat testes cells. However, no indication of DNA damage was visible.

Urinary glucaric acid excretion in rheumatoid arthritis: influence of disease activity and disease modifying drugs.

To examine if a correlation exists between cytochrome P-450 enzyme induction and disease activity in patients with rheumatoid arthritis (RA), measuring urinary excretion of D-glucaric acid (GA) as an index of phase II drug metabolism. Patients with RA were treated with sulphasalazine, sodium aurothiomalate, or D-penicillamine in standard dose regimens, for 24 weeks. Patients with ankylosing spondylitis (AS) or non-inflammatory arthritis (NIA) acted as controls. The urinary GA:creatinine ratio was measured at 0, 12, and 24 weeks of treatment. Patients with RA had a slightly greater urinary GA:creatinine ratio than patients with AS or NIA at baseline; this increased during treatment with disease modifying antirheumatic drugs (DMARDs). Sulphasalazine treatment had a greater effect on GA excretion than sodium aurothiomalate or D-penicillamine; this difference was statistically significant between weeks 0 and 12 (p = 0.01). Gamma glutamyltranspeptidase concentration showed a weak correlation with GA excretion between weeks 0 and 12 (p = 0.03), but all other measurements of changes in disease activity (plasma viscosity, C reactive protein, platelets, and articular index) were found not to correlate with GA excretion between weeks 0-12 or 0-24. The increased excretion of GA in patients with RA receiving DMARD treatment is probably the result of an indirect effect on hepatic metabolism bearing no relationship to disease activity.

Biological Monitoring of Workers Exposed to N-Nitrosodiethanolamine in the Metal Industry

Biological monitoring of occupational hazards was performed in workers using cutting fluids containing N-nitrosodiethanolamine (NDELA). The study involved a group of 25 male subjects from some metal factories in central Italy who used cutting fluids with an NDELA content of &gt; or = 5 mg/l (high-exposure group) and a group of 37 males exposed to cutting fluids with an NDELA content &lt; 5 mg/l (low-exposure group). For comparison, we recruited a control group consisting of 37 subjects living in the same area. For all subjects, internal dose (urinary excretion of NDELA, mutagens, and thioethers), early biological effects (sister chromatid exchanges in blood peripheral lymphocytes), and urinary excretion of D-glucaric acid (DGA) as an endpoint product in the glucuronidation pathway were assessed. The results showed that only the workers using cutting fluids with NDELA concentrations of &gt; or = 5 mg/l excreted trace amounts of NDELA in their urine. Urine excretion of mutagens was similar in the two exposure groups and in the controls. High-exposure subjects had a higher mean value of urinary thioethers than low-exposure and control subjects, but no differences were found in urinary DGA or lymphocyte sister chromatid exchange among the three groups. Smoking status increased the mean values of all the biomarkers, and coffee drinking was associated with urinary DGA excretion.

Specific and dose-dependent enzyme induction by omeprazole in human beings

Omeprazole induces hepatic cytochrome P-4501A2. In a previous study this effect was shown to be significant in vivo in 6 poor metabolizers, including 1 intermediate metabolizer, but not in 12 extensive metabolizers of S-mephenytoin after 7 days of treatment with 40 mg/day omeprazole. In this study, the specificity of the inducing potential of omeprazole was investigated in these volunteers. Furthermore, in eight of the extensive metabolizers the dose-dependence of cytochrome P-450 1A2 induction was evaluated. Cytochrome P-450 1A2 activity was monitored by means of the 13C-[N3-methyl]caffeine breath test and by means of plasma caffeine clearance before omeprazole treatment with 120 mg/day, on the seventh day of dosage and after a 7-day washout. Omeprazole plasma concentration was measured. Results were compared with those after 40 mg. gamma-Glutamyltransferase activity in serum, as well as urinary excretion of D-glucaric acid and 6 beta-hydroxycortisol, were measured on the same study days in all study groups (n = 26). In the eight extensive metabolizers the breath test indicated a dose-dependent increase of cytochrome P-450 1A2 activity of 8.5% +/- 15.0% (40 mg, mean +/- SD, NS) and 27.2% +/- 16.5% (120 mg, p = 0.002). Caffeine clearance was increased by 31.6% +/- 20.7% (p < 0.001) with the higher dose. None of the study groups exhibited a significant increase of gamma-glutamyltransferase activity or urinary excretion of D-glucaric acid or 6 beta-hydroxycortisol. This was in contrast to the phenobarbital-type induction observed after treatment with antiepileptic drugs. Induction by omeprazole seems to be restricted to cytochrome P-450 1A enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Specific and dose-dependent enzyme induction by omeprazole in human beings

Omeprazole induces hepatic cytochrome P-4501A2. In a previous study this effect was shown to be significant in vivo in 6 poor metabolizers, including 1 intermediate metabolizer, but not in 12 extensive metabolizers of S-mephenytoin after 7 days of treatment with 40 mg/day omeprazole. In this study, the specificity of the inducing potential of omeprazole was investigated in these volunteers. Furthermore, in eight of the extensive metabolizers the dose-dependence of cytochrome P-450 1A2 induction was evaluated. Cytochrome P-450 1A2 activity was monitored by means of the 13C-[ N3-methyl]caffeine breath test and by means of plasma caffeine clearance before omeprazole treatment with 120 mg/day, on the seventh day of dosage and after a 7-day washout. Omeprazole plasma concentration was measured. Results were compared with those after 40 mg. γ-Glutamyltransferase activity in serum, as well as urinary excretion of d-glucaric acid and 6β-hydroxycortisol, were measured on the same study days in all study groups (n = 26). In the eight extensive metabolizers the breath test indicated a dose-dependent increase of cytochrome P-450 1A2 activity of 8.5% ± 15.0% (40 mg, mean ± SD, NS) and 27.2% ± 16.5% (120 mg, p = 0.002). Caffeine clearance was increased by 31.6% ± 20.7% (p < 0.001) with the higher dose. None of the study groups exhibited a significant increase of γ-glutamyltransferase activity or urinary excretion of d-glucaric acid or 6β-hydroxycortisol. This was in contrast to the phenobarbital-type induction observed after treatment with antiepileptic drugs. Induction by omeprazole seems to be restricted to cytochrome P-450 1A enzymes. Thus cytochrome P-450 1A2 induction is not clinically relevant with common therapeutic doses in EMs but might be of relevance after extraordinarily high doses or in poor metabolizers of S-mephenytoin.

Determinants of urinary thioethers, D-glucaric acid and mutagenicity after exposure to polycyclic aromatic hydrocarbons assessed by air monitoring and measurement of 1-hydroxypyrene in urine: a cross-sectional study in workers of coke and graphite-electrode-producing plants.

A cross-sectional epidemiological study was performed on 286 workers from two coke oven and one graphite electrode plants. The aim was to evaluate the usefulness of monitoring 1-hydroxypyrene (1-HOP) in urine for assessing exposure to polycyclic aromatic hydrocarbons (PAHs), and that of the urinary excretion of thioethers and D-glucaric acid, and the mutagenic activity of urine as indicators or biological effects of PAHs. The results confirm that 1-HOP determination in urine probably reflects exposure to PAHs by all routes and is not significantly influenced by the smoking habit. In comparison with the total PAHs in the air and 1-hydroxypyrene in urine, taken as reference exposure parameters, the results indicate that urinary D-glucaric acid excretion is not positively influenced by PAHs exposure; thioethers determination in urine is of poor value, since the smoking habit is a strong confounding factor. The determination of urinary mutagenicity might contribute to the detection of groups of workers exposed to potentially genotoxic PAHs.

Sister chromatid exchanges in lymphocytes of petroleum retailers.

Occupational exposure to petroleum vapour was assessed in workers employed in suburban petroleum retail outlets. Urinary output of thioethers provided a non-specific estimate of exposure to chemicals metabolised via a mercapturic acid pathway. Urinary d-glucaric acid (DGA) excretion was taken as an estimate of hepatic enzyme activity. Sister chromatid exchange frequency in lymphocytes was used as an indicator of genotoxic response to exposure. Workers were classified according to their employment at self service (where customers operate petrol pumps) or at driveway attended service stations (at which an employee operates the pumps), and according to exposure to cigarette smoke on the basis of urinary cotinine excretion. Prework and postwork urine samples of workers employed at driveway attended petrol stations contained more thioether than did those of self serve workers. When classified according to smoking behaviour there were no statistically significant differences, although thioether excretion tended to be higher in smokers than in nonsmokers. Urinary DGA excretion was similar in the two exposure groups. Cigarette smokers excreted more DGA, however, than nonsmokers. Sister chromatid exchange frequencies were higher in driveway attendants than in self serve personnel. When the influence of cigarette smoking was investigated there was a significant increase of sister chromatid exchange with combined exposure to petrol and cigarette smoking, but not with either factor alone. Correlation analysis showed that urinary cotinine concentrations were positively associated with urinary excretion of thioether and DGA, indicating that cigarette smoke induces the activity of hepatic enzymes and acts as a source of substrates metabolised through a thioether pathway. In conclusion it seems that exposure to petroleum vapour causes increased sister chromatid exchange in circulating lymphocytes of cigarette smokers, possibly as a result of enhanced hepatic conversion of vapour components to reactive metabolites. Urinary thioether output does not clearly discriminate between workers exposed to different amounts of petroleum vapour at retail outlets.

Urinary D-glucaric acid, a marker substance for microsomal enzyme induction. Methodological aspects, responses to alcohol and findings in workers exposed to toluene.

D-glucaric acid, an end product of glucuronic acid metabolism, has been used as a marker substance for microsomal enzyme induction. In this study a convenient microtitre-plate based method for the quantification of urinary D-glucaric acid has been developed and validated. Mean urinary D-glucaric acid excretion in 20 health humans as measured by this method was 3.2 mumol glucaric acid mmol-1 creatinine, 95% confidence interval 3.0-3.4. Moderate alcohol consumption in 18 healthy volunteers did not significantly augment the urinary D-glucaric acid excretion. Occupational exposition to toluene in a printing plant was investigated. In spite of considerable intra- and inter-individual variability, a significant difference between exposed (3.5, 3.1-3.9) and non-exposed (2.6, 2.2-3.0) workers was observed, p < 0.025. We conclude that the measurement of D-glucaric acid can be utilized for biological screening of enzyme induction on a group basis.

Occupational Exposure of Operating-Theater Personnel to Isoflurane and Nitrous Oxide

Abstract Liver-function abnormalities have been observed in humans exposed to inhalation anesthetics and experimental studies have revealed changes in microsomal enzyme-system activity caused by inhalation of a variety of anesthetics. This study assessed liver function by means of a simple noninvasive test: measuring urinary D-glucaric acid (UDGA) excretion in 24 subjects [selected from an anesthesia staff and exposed to a mixture of anesthetics of about 1 ppm (40 mmol/m3) of isoflurane (Forane®) and below 100 ppm (4090 mmol/m3) of nitrous oxide] matched with 24 controls. In the exposed group the postoperative UDGA mean level (3.68 mmol/mol creatinine) was significantly (p < 0.05) increased compared to the preoperative mean level (2.92 mmol/mol creatinine), which did not differ from the controls' mean level (2.83 mmol/mol creatinine). Concerning the difference between UDGA concentration in urine collected before and after exposure (ΔUDGA), the majority of the subjects (8 out of 9) included in the lowest e...

ビタミンC負荷尿中D-グルカリン酸排泄量によるチトクロームP-450活性値の測定

ビタミンC負荷尿中D-グルカリン酸排泄量によるチトクロームP-450活性値の測定

Exposure to toluene increases the urinary excretion of D-glucaric acid.

Workers at a printing plant exposed to low concentrations of toluene (43-401 mg/m3, median 155 mg/m3) had increased urinary D-glucaric acid (3.55-5.12 mmol/mol creatinine) excretion at the end of the shift compared with controls (2.45-3.35 mmol/mol creatinine). No increase was found after the summer holiday (1.92-2.89 mmol/mol creatinine) but excretion had increased two weeks later (4.05-5.55 mmol/mol creatinine). These changes in the excretion of D-glucaric acid were not correlated to levels of exposure, to changes of urinary hippuric acid and o-cresol half lives (three to eight hours), nor to o-cresol/hippuric acid concentration ratios when measured at the end of daily exposure. Since a significant intra and interindividual variability of urinary D-glucaric acid was found in all groups, urinary D-glucaric acid excretion is suitable to monitor group but not individual exposure.

Urinary excretion of mutagens, thioethers and D-glucaric acid in workers exposed to bitumen fumes.

The authors carried out biological monitoring of the mutagenic/carcinogenic hazards associated with exposure to bitumen fumes during paving operations, analysing some biological parameters in the urine of a group of exposed workers. The urine samples were studied for mutagenicity by the Ames test and for thioethers concentration. D-Glucaric acid urine excretion was also determined to investigate the enzymatic induction potential of bitumens. Even though, in a previous environmental monitoring phase, a low content of mutagenic/carcinogenic compounds was found in bitumen and air samples, urinary mutagenicity data of exposed workers were statistically higher than those of a group of unexposed subjects. The urinary mutagenicity increased further if exposure to bitumens was associated with cigarette smoking. Thioethers were higher only in subjects exposed simultaneously to bitumens and cigarettes. D-Glucaric acid excretion did not increase significantly. The authors think that this type of coupled environmental and biological monitoring is a valid tool for a better evaluation of the mutagenic/carcinogenic exposure to bitumens or similar complex mixtures.

Caffeine consumption and vegetarian diets affect D-glucaric acid excretion in man

The urinary excretion of D-glucaric acid (DGA) has been used as a nonspecific measure of the induction of hepatic enzymes associated with drug metabolism in man. A survey of 124 nonmedicated men (18–56 years of age), who kept a 5-day food, beverage, and drug intake record and collected their total urinary output for the last three days of the five, was conducted to assess the relationship between DGA excretion and various dietary factors. Eighteen nonmedicated healthy women collected the same data, but started on the eighth day from the commencement of menstruation. DGA was determined by an enzymatic assay and recorded as umoles D-glucaro-1,4-lactone/g creatinine. A positive association was found between total DGA excreted and the use of marijuana, caffeine, and tobacco products, the heaviest users excreting higher levels of urinary DGA than the moderate or low users of the same substance (P<0.05). Analysis of variance of mean DGA excretion also revealed differences (P<0.05) between females (17.0±3.7) and males (14.3±5.2); male vegetarians (17.4±5.5) and nonvegetarians (13.9±5.1); and female vegetarians (19.8±4.6) and nonvegetarians (16.2±3.1). Ethanol consumption did not relate to increased DGA excretion in either sex. Multiple regression analysis revealed that vegetarianism and caffeine consumption were the two strongest predictors of DGA excretion accounting for 32 percent of the total variance (P<0.005), while ethanol and marijuana consumption affected DGA the least. These results indicate that dietary and environmental factors may cause important changes in DGA excretion, and these changes may identify dietary inducers of hepatic enzymes associated with drug, xenobiotic and carcinogen biotransformations in humans.