Toxicokinetics of toluene and urinary excretion of hippuric acid after human exposure to 2H8-toluene.

Nine male volunteers were exposed to 2H8-toluene (200 mg/m3 for two hours during a workload of 50 W) via inspiratory air with the aid of a breathing valve and mouthpiece. Labelled toluene was used to differentiate between hippuric acid originating from exposure to toluene and hippuric acid normally excreted in urine. The total uptake of toluene was 2.2 (standard deviation (SD) 0.2) mmol, or 50% of the amount inhaled. Four hours after the end of exposure 1.4 (SD 0.3) mmol or 65% of the total uptake had been excreted in urine as 2H-hippuric acid and 20 hours after the end of exposure the cumulative excretion of 2H-hippuric acid was 1.8 (SD 0.3) mmol, or 78% of the total uptake. By contrast the cumulative excretion of labelled plus unlabelled hippuric acid exceeded the total uptake of toluene already after four hours. The excretion rate of 2H-hippuric acid was highest, about 5 mumol/min, during exposure and the SD between the subjects was low. The background concentrations of unlabelled hippuric acid in urine were high, however, and there were large differences between subjects. These findings confirm earlier indications that for low exposure, urinary hippuric acid concentration cannot be used for biological monitoring of exposure to toluene.     

Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats.

Rats were exposed to toluene at a wide range of concentrations from 50 to 4000 ppm for six hours, and the effects of ethanol and phenobarbital (PB) treatments on the pharmacokinetics of toluene metabolism were investigated. Ethanol treatment influenced toluene metabolism mainly at low exposure concentrations. Thus ethanol accelerated the clearance of toluene from blood only when the blood concentration of toluene was not high (less than 360 microM), and ethanol increased hippuric acid (HA) excretion in urine more significantly at low (less than 250 ppm) than at high atmospheric toluene concentrations. Ethanol also expressed a similar effect on p-cresol excretion as on HA, but had little effect on o-cresol. Phenobarbital treatment promoted the urinary excretion of all of the metabolites of toluene, especially after exposure to high toluene concentration. As well as HA, benzoylglucuronide (BG) and free benzoic acid were found in urine. These are the products of the side chain metabolism of toluene. Amounts of BG could be detected when the urinary excretion of free benzoic acid exceeded 5 mumol/kg/6 h, indicating that a great deal of benzoic acid is required for the formation of BG. The Michaelis constant (Km) and the maximum rate of metabolic excretion in urine during six hours exposure (Vmax) of isozymes involved in the excretion of toluene metabolites were calculated, and correlated with the subtypes of cytochrome P-450. The significance of the result was suggested in the biological monitoring of exposure to toluene.     

Effect of ethanol,cimetidine and propranolol on toluene metabolism in man

Summary In a climatic exposure chamber four healthy volunteers were exposed to 100ppm toluene, 100ppm toluene + ethanol, 100ppm toluene + cimetidine, and 100ppm toluene + propranolol for 7h each at random over four consecutive days. A control experiment and 3.5 h of exposure to 200 ppm toluene were also performed. Ethanol inhibited toluene metabolism by 0.5 as expressed by the urinary excretion of two of the metabolites of toluene, namely o-cresol and hippuric acid. In agreement with this, the mean alveolar concentration of toluene was greater by 1.7 during ethanol exposure; 45 min after discontinuation of exposure the increase was by 3.3. Neither cimetidine nor propranolol changed toluene metabolism significantly. The results indicate that ethanol may prolong the time interval in which toluene is retained in the human body in persons simultaneously exposed to ethanol and toluene. When using o-cresol or hippuric acid in biological monitoring of persons occupationally exposed to toluene, the consumption of ethanol should be considered.Supported by grants from the Working Environment Fund, Denmark     

Three fatal cases of thinner-sniffing,and experimental exposure to toluene in human and animals

Summary Three fatal cases of organic solvent abuse revealed high levels of toluene in blood and alveolar air and a high level of hippuric acid, metabolite of toluene, in urine. The lethal concentration of toluene was estimated to be 2,000 ppm.Furthermore, 10 male and female volunteer students were exposed to 107 ±12 ppm toluene for 4 hours. Hippuric acid in urine increased with the exposure time and reached maximum 2 hours after initiation of toluene exposure and remained at the same level thereafter. Following cessation of exposure to toluene, hippuric acid in urine showed a rapid decrease and recovered almost to the normal level 4 hours after cessation of exposure.Urinary excretion of hippuric acid in 7 rabbits exposed to 350 ppm for 100 minutes or to 4,500 ppm toluene for 10 minutes, reached its maximum 1.5–2 hours after initiation of exposure and decreased rapidly after cessation of exposure to toluene to recover to the normal level 4 hours later.Read before the 43rd Annual Meeting of Japanese Association of Industrial Health at Tokushima on April 2, 1970, and the 18th Annual Meeting of North Kanto Medical Association at Maebashi on November 14, 1971.     

Effects of ethanol and phenobarbital treatments on the pharmacokinetics of toluene in rats.

Rats were exposed to toluene at a wide range of concentrations from 50 to 4000 ppm for six hours, and the effects of ethanol and phenobarbital (PB) treatments on the pharmacokinetics of toluene metabolism were investigated. Ethanol treatment influenced toluene metabolism mainly at low exposure concentrations. Thus ethanol accelerated the clearance of toluene from blood only when the blood concentration of toluene was not high (less than 360 microM), and ethanol increased hippuric acid (HA) excretion in urine more significantly at low (less than 250 ppm) than at high atmospheric toluene concentrations. Ethanol also expressed a similar effect on p-cresol excretion as on HA, but had little effect on o-cresol. Phenobarbital treatment promoted the urinary excretion of all of the metabolites of toluene, especially after exposure to high toluene concentration. As well as HA, benzoylglucuronide (BG) and free benzoic acid were found in urine. These are the products of the side chain metabolism of toluene. Amounts of BG could be detected when the urinary excretion of free benzoic acid exceeded 5 mumol/kg/6 h, indicating that a great deal of benzoic acid is required for the formation of BG. The Michaelis constant (Km) and the maximum rate of metabolic excretion in urine during six hours exposure (Vmax) of isozymes involved in the excretion of toluene metabolites were calculated, and correlated with the subtypes of cytochrome P-450. The significance of the result was suggested in the biological monitoring of exposure to toluene.     

Ethanol induced modification of m-xylene toxicokinetics in humans.

This study was undertaken to determine whether previous subacute treatment with ethanol could modify the kinetics of m-xylene in humans. A group of six volunteers was exposed twice to either 100 or 400 ppm of m-xylene during two hours (between 0800 and 1000). Ethanol was given orally in the early evening on each of two consecutive days before exposures (total ethanol intake of 137 g). Such ethanol pretreatment affected the kinetics of m-xylene but only at the high exposure (400 ppm). The modifications were: (1) decreased concentration of m-xylene in blood and alveolar air during and after exposure; (2) increased urinary excretion of m-methylhippuric acid at the end of exposure. Ethanol treatment also enhanced the elimination of antipyrine in saliva. Overall, this study showed that the effect of enzyme induction on the metabolism of m-xylene, after ethanol ingestion, depends on the exposure concentration and is not likely to occur as long as the exposure concentrations remain under the current maximum allowable concentration (100 ppm) in the workplace.     

Urinary excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure

Ogata, M., Tomokuni, K., and Takatsuka, Y. (1970).Brit. J. industr. Med.,27, 43-50. Urinary excretion of hippuric acid and m- or p-methylhippuric acid in the urine of persons exposed to vapours of toluene and m- or p-xylene as a test of exposure. Twenty-three male volunteers were exposed in groups of four or five to toluene and m- and p-xylene vapour for periods of 3 hours or of 7 hours with one break of an hour. Urine was collected at hourly intervals for several hours, and thereafter all urine was collected until 18 hours after the end of the exposure period, and was analysed for hippuric and methylhippuric acids. It was shown that hippuric acid was excreted equivalent to 68% of the toluene absorbed, and m-methylhippuric acid equivalent to 72% of the m-xylene absorbed. Up to hydrocarbon concentrations of 200 ppm the total quantity of hippuric acids excerted was proportional to the total exposure (ppm × hours). In descending order of precision the following were also related to exposure: rate of excretion during the exposure period; concentrations of hippuric acid in urine corrected to constant urine density; and concentrations in urine uncorrected for density. The last could not be used to calculate exposure, but the others could be to give screening tests to show whether workmen could have been exposed to concentrations greater than the maximum allowable.

The effects of exposure on blood pressure, pulse rate, flicker value, and reaction time were measured. There were some variations which suggested that the MAC of toluene should be set higher than 200 ppm.

     

Effect of ethanol on the urinary excretion of cyclohexanol and cyclohexanediols, biomarkers of the exposure to cyclohexanone, cyclohexane and cyclohexanol in humans.

OBJECTIVES: This study explored the acute effect of ethanol (EtOH) on the urinary excretion of cyclohexanol (CH-ol), 1,2- and 1,4-cyclohexanediol (CH-diol), biomarkers of exposure to important solvents, and chemical intermediates cyclohexanone (CH-one), cyclohexane (CH) and cyclohexanol. METHODS: Volunteers (5-8 in each group) were exposed for 8 hours either to CH-one, CH or CH-ol vapor at concentrations of about 200, 1000, and 200 mg/m3, respectively, with concomitant ingestion of EtOH (4 14-g doses taken during the exposure). Urine was collected for 72 hours and analyzed for CH-ol and CH-diols using a procedure involving acidic hydrolysis and gas chromatographic determination. RESULTS: The metabolic yields of CH-ol, 1,2-, and 1,4-CH-diol, respectively, in the exposures with EtOH were as follows: 11.3%, 36%, 23% after the exposure to CH-one, 3.1%, 15%, 8% after the exposure to CH, and 6.6%, 24%, 18% after the exposure to CH-ol. [The corresponding values obtained previously in matching experiments without EtOH were as follows: 1.0%, 39%, 18% (CH-one); 0.5%, 23%, 11% (CH); and 1.1%, 19%, 8% (CH-ol).] The excretion curves of the metabolites in the exposures with EtOH were not delayed when compared with the corresponding curves of a comparison group. CONCLUSIONS: The urinary excretion of CH-diols is much less sensitive to EtOH than that of CH-ol. It is recommended to employ CH-diols as useful and more reliable biomarkers of exposure to CH-one, CH and CH-ol in field examinations.     

Assessment of colour vision impairment in male workers exposed to toluene generally above occupational exposure limits

We investigated colour vision impairment in 45 male workersoccupationally exposed to toluene (mean value of toluene concentrationin ambient air=119.96 ppm) and in 53 controls. Colour visionwas evaluated by Lanthony-D-15 desaturated test and expressedas Age and Alcohol Intake Adjusted Colour Confusion Score (AACDS)or types of dyschromatopsia. Exposure was evaluated by measurementof toluene concentration in ambient air and blood, and hippuricacid and orthocresol determined in urine after the workshift.A statistically significant higher AACDS value was establishedin the exposed subjects compared to the controls (p<0.0001).There was no significant difference between AACDS values onWednesday morning compared to Monday morning. In the exposedgroup AACDS significantly correlated with the concentrationof toluene in ambient air, concentration of toluene in bloodand the concentration of hippuric acid in urine after the workshift(all p<0.0001). Dyschromatopsias were detected in both groups,although no significant difference between groups was established.In the exposed group, concentration of toluene in ambient air,alcohol intake and age explained 35.1%, concentration of toluenein blood, age and alcohol intake explained 19.9%, and concentrationof hippuric acid in urine and age explained 19.2% of the variationin type III dyschromatopsia. Concentration of toluene in ambientair and age explained 28.3% of the variation in total dyschromatopsia,and concentration of hippuric acid and age explained 13.8%.In the control group, age and alcohol intake explained 19.6%of the variation in type III dyschromatopsia. In exposed workersa significant difference was found in the AACDS value comparedto controls. However, no significant difference was found inthe prevalence of colour vision loss in the yellow-blue and/orred-green axis. Based on the results of this study the authorsconclude that the effect of toluene on colour vision can bechronic and that the possible reparation period in colour visionimpairment is longer than 64 hours.     

Subclinical abnormalities in workers with continuous low-level toluene exposure

Short-term exposure to a high concentration (TWA > 100 ppm) of toluene can cause hepatotocixity and neurotoxicity in humans. Data on the effects of exposure to low levels of toluene, however, are controversial. In addition, few studies on the effects of toluene exposure on the autonomic nervous system have been conducted. Urine samples from 34 male factory workers in Taiwan who were exposed to low levels of toluene either intermittently (n = 13) or continuously (n = 21) were taken on a Monday morning after a 2-day hiatus and at the end of the workweek on Friday evening. Urinary hippuric acid levels were measured using high-performance liquid chromatography (HPLC). A complete blood work-up was also performed for each subject. The prevalence and severity of neurotoxic symptoms were investigated by a self-reported questionnaire, a neuropsychiatric battery, and sympathetic and peripheral nerve function tests. The mean value of urinary hippuric acid corrected for creatinine (Cr) was 0.34 ± 0.18 g/g Cr on Monday morning and 0.43 ± 0.26 g/g Cr on Friday evening. The difference in the mean value of urinary hippuric acid between the two periods (p < 0.01) and the odds ratio of impairment of sympathetic (OR = 4.13, p = 0.11) and peripheral nerves (OR = 6.94, p = 0.074) were higher in workers continuously exposed to toluene. In addition, workers who were continuously exposed to toluene had a lower mean platelet count (216 ± 41 × 10(6) /μL) than workers who were intermittently exposed (252 ± 40 × 10(6)/μL), (p = 0.018). Furthermore, there was a positive relationship between neurological abnormalities and a self-reported neuropsychiatric measurement (r = 0.35-0.66, p < 0.05) in all workers. These data suggest that continuous exposure to low levels of toluene may be associated with sympathetic and peripheral nerve dysfunction and sub-clinical hematological damage. Further research needs to be carried out regarding how chronic exposure to low-levels of toluene affects workers.     

TLC separation of hippuric, mandelic, and phenylglyoxylic acids from urine after mixed exposure to toluene and styrene.

A method using thin-layer chromatography is described to determine the concentration of hippuric acid, mandelic acid, and phenylglyoxylic acid present in the urine after occupational mixed exposure to toluene and styrene. These substances are known metabolites of toluene and styrene, and therefore the evaluation to mixed exposure to toluene and styrene may be carried out separating these metabolites beforehand. Procedures are proposed to separate the metabolites as follows: (1) separation of hippuric acid from mandelic acid, (2) separation of mandelic acid from phenylglyoxylic acid, and (3) separation of hippuric acid and mandelic acid from phenylglyoxylic acid. The developing reagent p-dimethylaminobenzaldehyde in acetic acid anhydride was used after separation on Kieselgel and Silicagel. The sensitivity of the method was 6 microgram of hippuric acid, 10 microgram of mandelic acid, and 7 microgram of phenylglyoxylic acid with an average recovery of 94%.     

Influence of coffee intake on urinary hippuric acid concentration

Intake of foods and drinks containing benzoic acid influences the urinary hippuric acid (HA) concentration, which is used to monitor toluene exposure in Japan. Therefore, it is necessary to control the intake of benzoic acid before urine collection. Recently, some reports have suggested that components of coffee, such as chlorogenic, caffeic, and quinic acids are metabolized to HA. In this study, we evaluated the influence of coffee intake on the urinary HA concentration in toluene-nonexposed workers who had controlled their benzoic acid intake, and investigated which components of coffee influenced the urinary HA concentration. We collected urine from 15 healthy men who did not handle toluene during working hours, after they had consumed coffee, and we measured their urinary HA concentrations; the benzoic acid intake was controlled in these participants during the study period. The levels of chlorogenic, caffeic, and quinic acids in coffee were analyzed by LC-MS/MS. Urinary HA concentration increased significantly with increasing coffee consumption. Spectrophotometric LC-MS/MS analysis of coffee indicated that it contained chlorogenic and quinic acids at relatively high concentrations but did not contain benzoic acid. Our findings suggest that toluene exposure in coffee-consuming workers may be overestimated.     

Effects of the exposure to polycyclic aromatic hydrocarbons or toluene on thiobarbituric acid reactive substance level in elementary school children and the elderly in a rural area]

OBJECTIVES: Polycyclic aromatic hydrocarbons (PAH) and toluene have been reported to induce reactive oxygen species and oxidative stress. This study was performed to investigate the effects of low level exposure to PAHs or toluene on the lipid peroxidation level in elementary school children and the elderly in a rural area. METHODS: Forty seven elementary school children and 40 elderly people who were living in a rural area and not occupationally exposed to PAH or toluene were the subjects of this study. Information about active or passive smoking and diet was obtained using a self-administered questionnaire. The urinary 1-hydroxypyrene (1-OHP), 2-naphthol, hippuric acid and thiobarbituric acid reactive substance (TBARS) concentrations were measured, and these values were corrected with the urinary creatinine concentration. RESULTS: In school children, the geometric means of the urinary 1-OHP, 2-naphthol, hippuric acid and TBARS levels were 0.02 micromol/mol creatinine, 0.47 micromol/mol creatinine, 0.14 g/g creatinine and 0.95 micromol/g creatinine, respectively. Those values for the elderly were 0.07 micromol/mol creatinine, 1.87 micromol/mol creatinine, 0.11 g/g creatinine and 1.18 micro mol/g creatinine, respectively. The mean levels of urinary 1-OHP, 2-naphthol and TBARS were significantly higher in the elderly subjects than in the children. The urinary TBARS level was not correlated with the urinary 1-OHP, 2-naphthol and hippuric acid, but they were correlated with the age of the subjects. CONCLUSIONS: These results suggest that low level inhalation exposure to PAH or toluene does not markedly increase lipid peroxidation, and age is a significant determinant of lipid peroxidation.     

Comparative evaluation of biomarkers of occupational exposure to toluene

Objectives This study was initiated to make comparative evaluation of five proposed urinary markers of occupational exposure to toluene, i.e., benzyl alcohol, benzylmercapturic acid, o-cresol, hippuric acid and un-metabolized toluene. Methods In practice, six plants in Japan were surveyed, and 122 Japanese workers (mostly printers; all men) together with 12 occupationally nonexposed control subjects (to be called controls; all men) agreed to participate in the study. Surveys were conducted in the second half of working weeks. Time-weighted average exposure (about 8 h) to toluene and other solvents were monitored by diffusive sampling. End-of-shift urine samples were collected and analyzed for the five markers by the methods previously described; simultaneous determination of o-cresol was possible by the method originally developed for benzyl alcohol analysis. Results The toluene concentration in the six plants was such that the grand geometric mean (GM) for the 122 cases was 10.4 ppm with the maximum of 121 ppm. Other solvents coexposed included ethyl acetate (26 ppm as GM), methyl ethyl ketone (26 ppm), butyl acetate (1 ppm) and xylenes (1 ppm). By simple regression analysis, hippuric acid correlated most closely with toluene in air (r = 0.85 for non-corrected observed values) followed by un-metabolized toluene (r = 0.83) and o-cresol (r = 0.81). In a plant where toluene in air was low (i.e., 2 ppm as GM), however, un-metabolized toluene and benzylmercapturic acid in urine showed better correlation with air-borne toluene (r = 0.79 and 0.61, respectively) than hippuric acid (r = 0.12) or o-cresol (r = 0.17). Benzyl alcohol tended to increase only when toluene exposure was intense. Correction for creatinine concentration or specific gravity of urine did not improve the correlation in any case. Multiple regression analysis showed that solvents other than toluene did not affect the levels of o-cresol, hippuric acid or un-metabolized toluene. Levels of benzylmercapturic acid and un-metabolized toluene were below the limits of detection [limit of detections (LODs); 0.2 and 2 μg/l, respectively] in the urine from the control subjects. Conclusions In over-all evaluation, hippuric acid, followed by un-metabolized toluene and o-cresol, is the marker of choice for occupational toluene exposure. When toluene exposure level is low (e.g., 2 ppm), un-metabolized toluene and benzylmercapturic acid in urine may be better indicators. Detection of un-metabolized toluene or benzylmercapturic acid in urine at the levels in excess of the LODs may be taken as a positive evidence of toluene exposure, because their levels in urine from the controls are below the LODs. The value of benzyl alcohol as an exposure marker should be limited.     

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.     

Chronic occupational exposure to toluene

Summary Chronic occupational exposure to toluene was studied in a factory preparing tarpaulins. Seventy-eight workers were studied; 46 were exposed to various concentrations of toluene in air (20–200 ppm), 32 were unexposed workers in the same factory. In many cases the exposure had lasted for 10–20 years. The urinary hippuric acid excretion at the end of work shift showed good correlations to toluene concentrations in air, and it seems to be a good measure of exposure. The hippuric acid in urine samples collected overnight showed that elimination of toluene still occurs several hours after exposure. Most of the biological parameters measured showed no correlation to toluene exposure. The blood leukocyte count did show slight positive correlations to toluene exposure, but even this parameter stayed inside the range of normal values. The occurrence of chronic diseases, drug using habits, and drinking and smoking habits did not show any correlations to toluene exposure.This study has been supported by the grant of Y. Jahnsson Foundation in Finland     

Effect of repeated exposure to methanol and toluene vapor on the metabolism of rats

Wistar male rats were repeatedly exposed to methanol and toluene vapors individually and simultaneously by inhalation 6 hours a day, five days a week for 4 weeks. Blood was obtained from the tail of the rats up to 23 hours after the end of 4-week exposure and the methanol and toluene concentrations were measured. Major metabolites of methanol and toluene, that is, formic acid and hippuric acid in urine were measured up to 6 days after the end of 4-week exposure. The biological half time of toluene in blood in the simultaneous exposure group was shorter than that in the toluene exposure group. This tendency was almost the same as that for one-day exposure, although the biological half time of solvents in the rat blood was prolonged. The half times of methanol were also longer than those for one-day exposure.     

Biological monitoring for occupational exposure to toluene

A study was undertaken to examine the relationship between exposure of workers to toluene in the work environment and biological indicators of toluene exposure. The biological indicators studied were toluene in expired air, toluene in blood obtained by the finger prick method, and urinary hippuric acid. The study was undertaken in a factory in Singapore that manufactures speakers for audio systems. A total of 86 female workers exposed to toluene at the workplace and a control group of workers not exposed to toluene were examined. All of them were teetotalers, were nonsmokers, and gave no history of chronic drug usage. The 8-hr time-weighted average exposure level of toluene ranged from 1.6 ppm to 263 ppm. The study showed the expected toluene levels in finger prick blood was 1.4 micrograms/mL after an 8-hr exposure to 100 ppm of toluene. Toluene concentration in expired air of 16 ppm after an 8-hr exposure to 100 ppm compared favorably with other studies. The toluene in blood/expired air ratio was observed to be lower than in other studies. In this study, the expected urinary hippuric acid level for a 100-ppm exposure to toluene was 2.7 g/g creatinine. This level is higher than that recorded in other studies. The results showed that at low levels of toluene, urinary hippuric acid is not a valuable indicator of exposure. Toluene in expired air is the most reliable biological indicator of exposure to toluene.     

A new derivatization procedure for the analysis of hippuric acid and m-methyl-hippuric acid by gas chromatography

Summary The industrial solvents, toluene and xylene, have physicochemical properties that can be hazardous to the workers exposed. Since hippuric acid and m-methyl-hippuric acid represent the products of toluene and xylene biotransformation in urine, they are used as biological markers in studies on occupational exposure to these solvents. Several methods have been used to determine hippuric acid and m-methyl-hippuric acid —either based on gas chromatography or on high-performance liquid chromatography. In this study we propose the derivatization of hippuric acid and methyl-hippuric acid using methanol in acid medium (HCl), a low-cost reagent with a low level of toxicity. The method has been routinely used in our laboratory for 1 year and has proven to be a reliable procedure for the biological control of occupational exposure to toluene and/or xylene.     

Effects of ethanol and low-carbohydrate diet on contents of noradrenaline, dopamine, serotonin and their metabolites in rat brain]

Effects of ethanol consumption and intake of low-carbohydrate (low-CHO) diet on noradrenaline (NA), dopamine (DA) and its metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), serotonin (5HT) and its metabolite, 5-hydroxyindoleacetic acid (5HIAA) contents in six brain regions of rats were investigated. 1) Change of DA neuron Ethanol-containing control diet (hypercaloric ethanol diet) did not affect DA content in any area of brain, but decreased HVA in cortex and hypothalamus and increased DOPAC and HVA in midbrain. Low-CHO diet increased DA content in striatum, DOPAC and HVA in midbrain, but decreased DOPAC in hippocampus and hypothalamus, and HVA in cortex, pons and medulla, hippocampus and hypothalamus. Ethanol-containing low-CHO diet (isocaloric ethanol diet) increased DA level in striatum, DOPAC and HVA in midbrain, but decreased HVA in cortex, hippocampus, striatum and hypothalamus. These results suggest that i) hypercaloric ethanol diet has an opposite effect to carbohydrate on DA metabolism: hypercaloric ethanol diet and lowered carbohydrate intake per se enhance DA metabolism in midbrain, whereas inhibit it in cortex and hypothalamus, ii) lowered carbohydrate intake also declines DA metabolism in pons and medulla and hippocampus, whereas enhances DA synthesis in striatum, iii) the combined effect of ethanol and carbohydrate intake on DA metabolism is inhibited each other in the rats of isocaloric ethanol diet feeding, and this diet decreased DA metabolism in striatum. 2) Change of 5HT neuron Hypercaloric ethanol diet did not affect the contents of 5HT and 5HIAA in any region of brain.(ABSTRACT TRUNCATED AT 250 WORDS)