흰쥐의 Toluene 간독성에 있어서 Taurine과 Ginseng의 효과

배시우 ( Si Woo Bae ),윤인숙 ( In Sook Yoon ) 대한임상검사과학회 2003 대한임상검사과학회지(KJCLS) Vol.35 No.2

Toluene is mainly metabolized in liver by oxidative pathway. Oxygen free radicals occur through the process of toluene metabolism. Therefore it causes tissue and cell injury by the oxygen free radicals from the metabolism of toluene. Taurine is a nonessential amino acid that is of medical interest for the nutrition of infants. Taurine is known as an antioxidant that prevents organ damage by scavenging reactive oxygen species. Ginseng is one of the most popular herbal remedies and ginseng has been used as a traditional medicine with various therapeutic effects. And there are interesting report that ginseng has antioxidant reaction. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if taurine and ginseng protect the rat`s liver, taurine and ginseng was administrated orally, at the time of each toluene injection. Aspartate aminotransferase (AST), alanine 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. AST, ALT, LDH and MDA levels were significantly higher in toluene group than in control group, but there were no significant differences between taurine and ginseng groups and control group. However LDH and MDA levels were significantly higher in taurine and ginseng groups than in control group. ALP levels were significantly lower in toluene and taurine groups than in control group. Hippuric acid levels were significantly higher in toluene, taurine and ginseng groups than in control group. But there were significantly lower in taurine and ginseng groups than in toluene group. Accordingly, the results suggest a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism. Taurine and red ginseng extract treatment significantly protected hepatic function and free radical-mediated injury in the rat`s liver against toluene-induced changes. Therefore, the results in this experiment suggest that taurine and red ginseng extract are effective in preventing the toluene-induced hepatotoxicity in a rat model.

The Beneficial Effect of Melatonin for Toluene Hepatotoxicity in Rats

Bae, Si-Woo,Yoon, In-Sook The Korean Society for Biomedical Laboratory Scien 2001 Journal of biomedical laboratory sciences Vol.7 No.3

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.

The Beneficial Effect of Melatonin for Toluene Hepatotoxicity in Rats

Bae, Si-Woo,Yoon, In-Sook 대한의생명과학회 2001 Biomedical Science Letters Vol.7 No.3

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 injury 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.

흰쥐의 톨루엔 간독성에 었어서 Vitamin C 와 E의 효과

배시우 ( Si Woo Bae ),윤인숙 ( In Sook Yoon ) 대한임상검사과학회 2002 대한임상검사과학회지(KJCLS) Vol.34 No.2

툴루엔은 주로 간에서 산화적 경로에 의해서 대사 된다. 활성산소는 톨루엔 대사과정에서 발생된다. 그러므로 툴루엔 대사과정에서 발생되는 활성산소에 의해 조직 및 세포상해를 야기 시킬 수 있다. Vitamin C와 E는 항산화제로 활성산소에 의한 손상으로부터 세표플 보호하는 데 고효율로 활성산소를 제거하는 역할을 한다. 툴루엔의 간 독성에 대한 가섣판검정하기 위해 툴루엔을 쥐의 복강에 주사하였다. 그라고 vitamin C와 E가 쥐간을 보호하는지를 알아보기 위해 쥐에게 톨루엔 주사와 함께 vitamin C와 E룰 경구 투여하였다. 간기능검사로 혈청 AST, ALT, LDH, ALP를 측정하였다. 산화적 손상의 간접지표인 MDA도 측정하였다. 툴루엔의 최종대사산물인 마뇨산은 매LC로 정량하였다. AST, ALT, LDH, MDA와 마뇨산은 툴루엔군이 대조군에 비해서 현저하게 높았다. 그러나 vitamin C와 E군에서는 ALT와 마뇨산을 제외하고는 현저한 차이는 없었다. ALP는 툴루엔군에서 현저하게 낮았으나 vitaminC와 E군에서는 현저한 차이는 없었다. 이상의 결과로 보아 툴루엔이 대사 될 때 활성산소에 의해 간 독성이 야기되었음을 알 수 있다. 그리고 vitamin C와 E를 투여했을 때 툴루엔으로 인한 간의 손상을 방어해 줌을 알 수 있다. 따라서 이 연구는 vitamin C 와 E 가 툴루엔에 의한 급성 간 중독시 간 손상을 방어하는 데 도움이 된다고 사료된다. Toluene is mainly metabolized in the liver by the oxidative pathway. Oxygen free radicals occur through the process of toluene metabolism. Therefore, tissue and cell injury occurs by oxygen free radicals from the metabolism of toluene. Vitamin C is a water-soluble antioxidant that maintains many metal cofactors in the reduced state. Vitamin E( -tocopherol) acts as an antioxidant, breaking free-radical chain reactions as a result of their ability to transfer a phenolic hydrogen to a peroxyl free radical of a peroxidasised polyunsaturated fatty acid. Therefore vitamin C and E act as highly efficient free radical scavengers that protect cells from damage by oxygen free radicals. To test this hypothesis, toluene hepatotoxicity was induced by an abdominal injection of toluene. To see if vitamin C and E protects the rat``s liver, vitamin C and E was administrated orally, at the time of each toluene injection. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), latic dehydrogenase (LDH) and alkaline phosphatase (ALP) levels in serum were measured to estimate hepatic function. Melondialdehyde (MDA), which gives an indirect index of oxidative injury was also measured. Hippuric acid, the last metabolic production of toluene, was measured by HPLC. There were significantly higher values in AST, ALT, LDH, MDA and hippuric acid in the toluene group, but the values were mostly lower in vitamin C and E groups than in toluene group. There were significantly lower values in ALP in the toluene group, but there were no significant differences between the vitamin C and E groups, suggesting a significant hepatotoxicity due to oxygen free radicals through the process of toluene metabolism. Vitamin C and E treatment significantly protected hepatic function and free radical-mediated injury in the liver against toluene-induced changes. Accordingly, this study shows that vitamin C and E is helpful in protecting against liver injury by acute toluene intoxication.

혐기성 미생물에 의한 toluene과 xylene 분해 특성

조경숙,조원실,류희욱 한국냄새환경학회 2004 실내환경 및 냄새 학회지 Vol.3 No.2

Six kinds of the microbial consortia were obtained from the enrichment culture using the mixture gases of toluene and xylene as sole carbon sources and sulfate as a final electron acceptor. The degradation rates of the mixture gases by the consortia were determined, and the microbial structure in the consortia were characterized using 16S rDNA PCR and denaturing gradient gel electrophoresis (DGGE). The enriched consortia could simultaneously degrade toluene and xylene in the mixture gases. The toluene and xylene degradation rates in the mixture gases were 24.6∼49.1 and 2.8∼6.2 μmol L-1 d-1, respectively. Nine clones among 15 clones, isolated from the enriched consortia, were affiliated with the bacteria related to the degradation of hydrocarbons, chlorinated solvent, trichlorobenzene and TCE. These clones are expected to play important roles on the anaerobic degradation of toluene and xylene in the consortium. Toluene과 xylene의 혼합가스를 유일 탄소원으로 하고, sulfate를 최종전자수용체로 공급한 조건에서 농화 배양하여 얻은 6 종류의 미생물 농화배양액의 toluene과 xylene분해 특성을 조사하고 미생물 군집 특성을 분자생물학적 방법을 이용하여 분석하였다. 본 연구에서 얻은 농화배양액은 toluene과 xylene을 동시에 분해할 수 있었고, toluene과 xylene 분해속도는 각각 24.6∼49.1 및 2.8∼6.2 μmol L-1 d-1이었다. 농화배양액으로부터 분리한 15개의 clone 중에서 9개의 clone이 탄화수소화합물, 염소계 용매, trichlorobenzene 및 TCE 분해와 관련된 세균들과 유사성이 높은 것으로 동정되었는데, 이들 clone이 toluene 및 xylene 혼합가스의 혐기성 생분해에 관여하고 있을 것으로 사료되었다.

초기 톨루엔 농도가 톨루엔-NOx-공기 혼합물의 광산화 반응에 미치는 영향 : I. 가스상 물질의 변화 I. Change of Gaseous Species

이영미,배귀남,이승복,김민철,문길주 한국대기환경학회 2005 한국대기환경학회지 Vol.21 No.1

An experimental investigation of the gas-phase photooxidation of toluene-NO_(x)-air mixtures at sub-ppm concentrations has been carried out in a 6.9 ㎥, indoor smog chamber irradiated by blacklights. Measured parameters in the toluene-NOx experiments included O₃, NO, NO₂, NO_(x), CO, SO₂, toluene, and air temperature. The initial toluene concentration ranged from 225 ppb to 991 ppb and the initial concentration ratio of toluene/NOx in ppbC/ppb was in the range of 5~20. It was found that the variation of gaseous species with irradiation time caused by the photooxidation of toluene-NOx-air mixtures depended on the initial toluene concentration for similar concentration ratio of toluene/NOx. The dependency of initial toluene concentration on the photooxidation of toluene-NO_(x)-air mixtures for toluene/NOx =5~6 seemed to be opposite to that for toluene/NOx=10~11. The arriving time at maximum ozone concentration depended on both initial toluene concentration and initial concentration ratio of toluene/NOx. However, the maximum concentration of ozone formed by photooxidation depended only on the initial toluene concentration.

흰쥐에 있어서 주정중독이 Toluene 대사에 미치는 영향

윤종국,윤선동,신중규 한국독성학회 1996 Toxicological Research Vol.12 No.2

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.

흰쥐에 있어서 Toluene대사에 미치는 주.야 시차의 영향

류종일,윤종국,신중규 THE KOREAN SOCIETY FOR BIOMEDICAL LABORATORY SCIEN 1999 Journal of biomedical laboratory sciences Vol.5 No.1

주·야 (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 toluene투여군 모두 높게 나타났으며, cytosol의 benzylalcohol dehydrogenase (BADH) 활성은 night phase군과 day phase군 간에 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 phase군에서는 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 phase군 간에는 별다른 차이를 볼 수가 없었다. 한편 toluene투여로 인한 체중 당간 무게 및 혈청 xanthine oxidase 활성 증가율은 night phase군이 day phase군 보다 높게 나타났다. 이상 실험결과를 종합해 볼 때 요 중 hippuric acid 함량이 주·야 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 사료되어진다. To investigate the effect of the circadian variations on the toluene metabolism, 50% toluene in olive oil (0.2ml/100 g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Each group of animals was sacrificed at 8 hr after last injection of toluene. Hepatic microsomal aniline hydroxylase activity was more increased in control rats of night phase than those of day phase. On the other hand, the activities of hepatic benzylalcohol dehydrogenase in control rats of night phase showed the similiar value with that in those of day phase and in case of toluene treatment, these enzyme activities in rats of night phase were rather more decreased than those of day phase. Furthermore, hepatic benzaldehyde dehydrogenase activities were more or less higher in the control rats of night phase than those of day phase and by toluene treatment, enzyme activities of rats of night phase were somewhat decreased than those of day phase. In vitro, benzylalcohol or benzaldehyde inhibited the activities of benzylalcohol or aldehyde dehydrogenase prepared from the rats liver supernatant. There were no differences in urinary hippuric acid contents between the night phase and day phase both in the control and toluene treated group. The increasing rate of liver weight per body weight (%), serum xanthine oxidase activities were higher in rats of night phase than in those of day phase by toluene treatment. In conclusion, these results indicate that the producing rate of benzylalcohol and benzaldehyde from toluene may be higher in rats of night phase than those of day phase.

흰쥐에 있어서 Toluene 대사에 미치는 주ㆍ야 시차의 영향

류종일(Jong-Ihl Ryu),윤종국(Chong-Guk Yoon),신중규(Joong-Kyu Shin) 대한의생명과학회 1999 Biomedical Science Letters Vol.5 No.1

주ㆍ야 (day, night phase) 시차에 따른 toluene 대사를 검토할 목적으로 흰쥐에 50% toluene (olive oil과 toluene의 동량혼합액)을 체중 100 g 당 0.2 ㎖씩 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 phase군 간에 별다른 차이를 볼 수 없었으나, toluene 투여시에는 night phase군이 day phas군 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 phase군 간에는 별다른 차이를 볼 수가 없었다. 한편 toluene 투여로 인한 체중 당 간 무게 및 혈청 xanthine oxidase 활성 증가율은 night phase군이 day phase군 보다 높게 나타났다. 이상 실험결과를 종합해 볼 때 요 중 hippuric acid 함량이 주ㆍ야 시차에 따라 별다른 차이가 없는데도 불구하고 toluene으로부터 benzylalcohl이 및 benzaldehyde 생성률이 day phase군 보다 night phase군이 높게 나타남으로서 toluene 대사산물에 의한 간 손상 정도가 day phase군 보다 night phase군이 높게 나타난 것으로 사료 되어진다. To investigate the effect of the circadian variations on the toluene metabolism, 50% toluene in olive oil (0.2 ㎖/100 g body weight) was intraperitoneally administered to the rats every other day for 6 days both in the night; 24:00 and the day; 12:00. Each group of animals was sacrificed at 8 hr after last injection of toluene. Hepatic microsomal aniline hydroxylase activity was more increased in control rats of night phase than those of day phase. On the other hand, the activities of hepatic benzylalcohol dehydrogenase in control rats of night phase showed the similiar value with that in those of day phase and in case of toluene treatment, these enzyme activities in rats of night phase were rather more decreased than those of day phase. Furthermore, hepatic benzaldehyde dehydrogenase activities were more or less higher in the control rats of night phase than those of day phase and by toluene treatment, enzyme activities of rats of night phase were somewhat decreased than those of day phase. In vitro, benzylalcohol or benzaldehyde inhibited the activities of benzylalcohol or aldehyde dehydrogenase prepared from the rats liver supernatant. There were no differences in urinary hippuric acid contents between the night phase and day phase both in the control and toluene treated group. The increasing rate of liver weight per body weight (%), serum xanthine oxidase activities were higher in rats of night phase than in those of day phase by toluene treatment. In conclusion, these results indicate that the producing rate of benzylalcohol and benzaldehyde from toluene may be higher in rats of night phase than those of day phase.

초기 톨루엔 농도가 톨루엔-NO_(x)-공기 혼합물의 광산화 반응에 미치는 영향 : II. 입자상 물질의 생성 및 성장 II. Aerosol Formation and Growth

이영미,배귀남,이승복,김민철,문길주 한국대기환경학회 2005 한국대기환경학회지 Vol.21 No.1

An experimental investigation of the gas-phase photooxidation of toluene-NOx-air mixtures at sub-ppm concentrations has been carried out in a 6.9 ㎡, indoor smog chamber irradiated by blacklights. Measured parameters in the toluene-NO_(x) experiments included aerosol, O₃, NO, NO₂, NO_(x), CO, SO₂, toluene, and air temperature. The initial toluene concentration ranged from 225 ppb to 991 ppb and the initial concentration ratio of toluene/NOx in ppbC/ppb was in the range of 5~20. It was found that the variation of aerosol number concentration with irradiation time caused by the photooxidation of toluene-NOx-air mixtures depended on the initial toluene concentration for similar concentration ratio of toluene/NO_(x). The dependency of initial toluene concentration on the photooxidation of toluene-NO_(x)-air mixtures for toluene/NOx=5~6 seemed to be opposite to that for toluene/NO_(x)= 10~11. The maximum number concentration of aerosols formed by photooxidation and the aerosol yield depended on both initial toluene concentration and initial concentration ratio of toluene/NO_(x). In this study, the aerosol yield, defined as aerosol formed per unit toluene consumed, was found to be 0.01~0.16.