Effect of Circadian Rhythms on the Toluene Metabolism in Rats

흰쥐에 있어서 Toluene 대사에 미치는 주.야 시차의 영향

To investigate the effect of the circadian variations on the toluene metabolism, 50％ toluene in olive oil (0.2 m1/100 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 dehydrngenase prepared from the rats liver supematant. 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.

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.