• Toxicological Research
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• 제31권1호
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• pp.25-32
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• 2015

The objectives of this study were to investigate the individual characteristics, lifestyle habits, exposure levels, and genetic diversity of xenobiotic-metabolizing enzymes involved in toluene metabolism in Korean and foreign workers exposed to toluene at a manufacturing plant. This study was conducted to determine the effects of culture or ethnicity on toluene metabolism. The results showed that blood and urinary toluene concentrations were dependent on the level of exposure to toluene. We analyzed the correlation between toluene metabolism and genetic diversity in glutathione S-transferase (GST) (M1), GSTT1, and cytochrome p-450 (CYP) $2E1^*5$ as well as lifestyle habits (smoking, drinking, and exercise habits). The results revealed significant correlations between toluene metabolism and GSTM1 and GSTT1 genetic diversity, as well as smoking and exercise.

• 대한의생명과학회지
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• 제7권3호
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• pp.99-102
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• 2001

Toluene is mainly metabolized in liver by oxidative pathway. Oxigen free radicals occur through the process of toluene metabolism Therefore it causes tissue and cell min by the oxygen free radicals from the metabolism of toluene. Melatonin acts as a highly efficient free radical scavenger that protects cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if the melatonin protects the rat's liver, melatonin was administrated orally, at the time of each toluene injection. Aspartate aminotransferase(AST), alanin aminotransferase(ALT), latic dehydrogenase(LDH) and alkaline phosphatase(ALP) levels in serum were measured to estimate hepatic function. Malondialdehyde(MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid is the last metabolic Production of toluene was measured by HPLC. There were significantly higher in AST, ALT, LDH, MDA and hippuric acid in toluene group, but there were no significant difference in melatonin group except ALT and hippuric acid. There was significantly lower in ALP level in toluene group, but there was no significant difference melatonin group, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism Melatonin treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that melatonin is helpful in protecting liver injury by acute toluene intoxication.

• Toxicological Research
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• 제12권2호
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• pp.243-250
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• 1996

To evaluate an effect of ethanol pretreatment on the toluene metabolism, toluene (50% in olive oil) was given three times at 0.2 ml/100g body weight at the interval of one day to the rats fed with 5% ethanol during two months. The ethanol pretreated rats were not identified particular liver injury by the histopathologic findings. In case of toluene treatment, the ethanol pretreatment to the rats led to more increased concentration of urinary hippuric acid than those treated with only toluene. The ethanol pretreatment to the rats led to the increased activities of hepatic aniline hydroxylase and these enzyme activities were higher both in toluene treated and those pretreated with ethanol, but no differences were found in two groups. Ethanol pretreated rats showed the more increased activities of benzylalcohol dehydrogenase than control group. Moreover, the ethanol pretreatment to the toluene treated rats led to significantly more increased activities of benzylalcohol dehydrogenase compared with those treated with toluene only. Furthermore, the alcohol pretreatment to the toluene treated rats also led to somewhat higher activities of benzaldehyde dehydrogenase than those treated with toluene. In conclusion, these results indicate that the chronic pretreatment of ethanol at not so much liver damage as normal may rather activate the toluene metabolism.

• Preventive Nutrition and Food Science
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• 제5권2호
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• pp.105-108
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• 2000

To evaluate an effect of oxygen free radical on the toluence metabolism, the rats were fed on a tungstate sup-plemented diet(0.75g of tungstate included in 1kg of standard diet) or a standard diet. To the present xanthine oxidase deficient animal model, toluene(0.15ml/100g of body weight) was injected and then the animals were sacrificed after 24 hrs to determine the toluene metabolizing enzyme activities and toluene metabolite, hippuric acid concentration. The increasing rate of urinary hippuric acid concentration was significantly(p<0.01) higher in tungstate fed animals than in standard diet fed ones. Hepatic cytochrome P_450 contents were significantly higher(p<0.01) in tungstate fed animals than in standard diet fed ones. And tungstate fed animals showed a ten-dency of higher activities of benzylalcohol dehydrogenase while a significantly higher activites of benzaldehyde dehydrogenase (p<0.01) than standard diet fed animals. In conclusion, the more possibly reduced oxygen free radical in toluene-treated rats fed with a tungstate supplemented diet than in those fed with a standard diet would be responsible for the enhancement of toluene metabolism.

• Toxicological Research
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• 제12권2호
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• pp.237-241
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• 1996

To study an effect of toluene administration on the toluene metabolism in rats liver previously fed a low (casein 7%, LP) or standard (casein 20%, SP) protein diet, toluene (50% in olive oil) was given at 0.2 ml per 100 g body weights once daily during 4 days to the male rats. The content of hepatic cytochrome P-450 was higher in rats fed SP than those fed LP. The hepatic benzylalcohol dehydrogenase activity was higher both in toluene-treated rats and its control group fed SP than those fed LP. The hepatic benzaldehyde dehydrogenase activity was somewhat higher in rats fed SP than those fed LP. In the case of toluene treatment, the increasing rate of hippuric acid contents to the control group were higher in rats SP than those fed LP. In conclusion, it is likely that the metabolic rate of toluene would be higher in rats fed SP than those fed LP.

• 한국산업보건학회지
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• 제7권1호
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• pp.61-69
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• 1997

흰쥐에 있어서 사염화탄소에 의한 간손상이 toluene 대사에 어떠한 영향을 미치는지를 알아보기 위하여 흰쥐에 $CCl_4$를 투여한 후 간기능 검사와 병리 조직 검사를 통하여 간손상이 확인되었다. 이같은 간손상 모델 실험동물에 toluene을 투여한 뒤 24시간 후 처치한 다음 요 중 hippuric acid 함량을 측정한 결과, 간손상이 유도된 후 흰쥐에 toluene을 투여한 실험군에 있어서 요 중 hippuric acid 함량이 toluene만 투여한 군 보다 현저히 감소되었다. 이때 toluene 대사에 관여하는 간조직의 cytochrome P-450에 상응하는 aniline hydroxylase 및 aminopyrine demethylase 활성과 benzylalcoh이 및 benzaldehyde dehydrogenase 활성 역시 간손상이 유도된 흰쥐에 있어서 유의하게 감소되었다. 또한 benzaldehyde dehydrogenase 활성의 kinetics를 관찰한 결과, 간손상이 유도된 실험동물 및 대조군 모두 유사한 $K_m$치를 보였으나 $V_{max}$치는 간손상이 유도된 실험동물에서 낮게 나타났다. 이상 실험결과를 종합하여 볼 때 $CCl_4$에 의한 간손상시 toluene 대사가 억제되며 이는 toluene 대사에 관여하는 효소단백합성 억제에 기인된 결과로 사료된다.

• 한국산업보건학회지
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• 제8권2호
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• pp.296-305
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• 1998

흰쥐에 있어서 toluene 또는 ethanol 전처치가 toluene 대사에 어떠한 영향을 미치는지를 검토하는 일환으로 흰쥐에 toluene 또는 ethanol을 경시별로 4주간 투여한 다음, 톨루엔을 1회 재투여한 후 처치하여 다음과 같은 결과를 얻었다. 즉, 간조직의 광학 및 전자현미경을 통한 병리조직학적 소견과 체중당 간무게, 혈청 alanine aminotransferase 활성 및 간조직 중 glutathione 함량 변동을 관찰한 결과, toluene 및 ethanol 전처치군 모두 가역적 간손상 정도가 관찰되었으며 톨루엔 및 에탄올 전처치군 간에 간손상 정도 차이는 볼 수 없었다. 이러한 실험동물 모델에서 toluene 및 ethanol 전처치군 모두 요 중 마뇨산 농도가 대조군 보다 높게 나타났으며 toluene 대사에 관여하는 간조직의 cytochrome P-450 함량 및 benzylacohol(BAD) 또는 benzaldehyde dehydrogenase(BzAD) 활성치가 대조군 보다 높게 나타났다. 그리고 요 중 마뇨산 농도와 BAD 및 BzAD 의 활성치는 톨루엔 전처치군이 에탄올 전처치군 보다 전 실험기간 동안 대체로 다소 높게 나타났다. 또한 간조직의 benzylalcohol dehydrogenase의 반응속도를 관찰한 결과 $V_{max}$치는 toluene 및 alcohol 전처치군 모두 대조군 보다 높게 나타났다. 이상 실험결과를 종합해 볼 때 실험동물에 toluene 및 ethanol 전처치가 toluene 대사를 촉진시키며 이는 toluene 대사에 관여하는 효소활성에 영향을 미쳐 나타난 결과로 생각된다.

• 대한의생명과학회지
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• 제5권1호
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• pp.67-74
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• 1999

주ㆍ야 (day, night phase) 시차에 따른 toluene 대사를 검토할 목적으로 흰쥐에 50% toluene (olive oil과 toluene의 동량혼합액)을 체중 100 g 당 0.2 ml씩 밤 12시, 낮 12시에 각각 투여한 다음 각각 8시간 후에 처치하여, 다음과 같은 결과를 얻었다. 간 microsomal aniline hydroxylase 활성은 night phase군이 day phase군 보다 대조군 및 toluene 투여군 모두 높게 나타났으며, cytosol의 benzylalcohol dehydrogenase (BADH) 활성은 night phase군과 day phase군간에 별다른 차이를 볼 수 없었으나, toluene 투여시에는 night phase군이 day phase군 보다 효소의 활성도가 오히려 억제되었다. 또한 간 조직의 benzaldehyde dehydrogenase (BALDH) 활성은 night phase군이 day phase군 보다 다소 높게 나타나는 경향을 보였으며, toluene 투여시에는 night phase군에서는 대조군 보다 오히려 감소되었으나 day phase 군에서는 높게 나타나는 경향을 보였다. 그리고 in vitro 시험에서 benzylalcohol 및 benzaldehyde가 BADH 및 BALDH 활성을 억제시킴이 관찰되었다. 요 중 hippuric acid 함량은 대조군 및 toluene 투여군 모두 night phase군과 day phase군간에는 별다른 차이를 볼 수가 없었다. 한편 toluene 투여로 인한 체중 당간 무게 및 혈청 xanthine oxidase활성 증가율은 night phase군이 day phase군 보다 높게 나타났다. 이상 실험결과를 종합해 볼 때 요 중 hippuric acid함량이 주ㆍ야 시차에 따라 별다른 차이가 없는데도 불구하고 toluene으로부터 benzylalcohol 및 benzaldehyde 생성률이 day phase군 보다 night phase군이 높게 나타남으로서 toluene 대사산물에 의한 간 손상 정도가 day phase군 보다 night phase군이 높게 나타난 것으로 사료되어 진다.

• Toxicological Research
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• 제14권3호
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• pp.321-328
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• 1998

This study was performed to evaluate the effect of liver damage on toluene metabolism in rats pretreated with carbon tetachloride. Liver damage in rats was induced by administration of 0.1ml of carbon tetrachloride per 100g of body wight intraperitoneally every day for four weeks except the last day before sacrifice. One day before sacrifice, toluene was administered to the animals instead of carbon tetrachloride. Rats were sacrificed at the 1st, the 2nd, the 3rd and the 4th week after the first administration of carbon tetachloride. Based on the histopathological findings, liver weight and serum alanine aminotransferase, the $CCl_4$-preteated group was found to have gradual severe liver damage. Especially the degree of liver injury became increasingly severe throughout the whole course of the experiment. The contnts of hippuric acid in urine lower in the all groups pretreated with $CCl_4$than that of the control. The contents of hepatic cytochrome P450(CYP), benzylalcohol dehydrogenase and benzaldehyde dehydrogenase activities were decreased in $CCl_4$-pretreated rats than those of the control. The $CCl_4$treated animals showed the gradual decreased activities of these enzyme as injection times elapsed. Km values of the benzylalcohol dehydrogenase in pooled liver samples from $CCl_4$-pretreated or control groups were similar. On the other hand, Vmax values of the $CCl_4$-pretreated group was lower than of the control. Therefore, it can be concluded that reduction of the toluene metabolism in damaged rat liver induced with $CCl_4$was due to the inhibition of CYP content, bezylalcohol and benzaldehyde dehydrogenase activities which related with toluene metabolic enzyme system.

• Journal of Preventive Medicine and Public Health
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• 제21권1호
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• pp.152-162
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• 1988

Benzene and toluene, which are widely used aromatic hydrocarbons in workplace, are recently proved to cause health hazards due to their toxic effects. This study investigated the influence of toluene on the urinary excretion of benzene metabolite by administering short term exposure limit(STEL) of these compounds(i.e., 13.8mg/kg of benzene and 108.8 mg/kg of toluene) intraperitoneally into Sprague-Dawley rats. After administration, urinary phenol concentration of rat was measured by gas chromatography for every three hours. Data were analyzed by non-parametric statistical methods using Kruskal-Wallis multi-sample test and Mann-Whitney U test. The following results were obtained : 1. Administration of STEL-benzene increased urinary phenol concentration in lats. 2. Urinary phenol concentration was increased logarithmically according to the dosage of benzene. 3. Excretion of phenol in urine was decreased when benzene and toluene were administered simultaneously compared with administering benzene alone. In summary, these results reveal that administration of STEL of toluene has antagonistic effect of urinary excretion of benzene metabolite in rats.