Studies on the Relationship of Lipid Peroxidation and Drug Metabolizing Enzyme in Regenerating Rat Liver

재생중인 흰쥐간의 Lipid Peroxidation과 약물대사효소의 상관관계에 관한 연구

The activities of aminopyrine demethylase which is marker enzyme of the microsomal drug-metabolizing system, NADPH-cytochrome a reductase and glutathione peroxidase were measured during the course of liver regeneration after about seventy percent hepatectomy in Wistar rats. In addition, the extent of lipid peroxidation and contents of cytochrome P-450 were also measured. Partial hepatectomy produced a significant depression in aminopyrine demethylase, to reach a minium about 24 hours after operation, but this activity was increased to normal value during regeneration. On the other hand, in sham-operated animals, this showed no change. All the activities of NADPH-chrome P-450 contents of liver microsomes were rapidly decreased at the early stage of regeneration. These values returned to normal after 7 days. By contrast, the activity of glutathione peroxidase was nearly unchanged. According to these results, at the early stage of regeneration, the decrease of cytochrome P-450 and NADPH-cytochrome c reductase activity lead to decrease of lipid peroxidation and drug metabolizing enzyme activity. But these phenomena were not detected after 7 days of regeneration.

Wistar계 흰쥐 간의 약 70%를 절제한 후 재생중인 나머지 간의 microsome에서 lipid peroxidation과 약물 대사효소중 특징적인 aminopyrine demethylase의 활성도를 측정하고 NADPH-cytochrome c reductase, glutathione peroxidase의 활성도와 cytochrome P-450의 함량을 측정하였다. Aminopyrine demethylase의 활성도는 재생 제1일에 최저치를 나타냈으며 재생이 진행될수록 정상인 수준으로 증가하였고 lipid peroxidation, NADPH-cytochrome c reductase, cytochrome P-450의 함량 역시 재생초기에 급히 감소하여 재생2일에 가장 낮은 값을 나타내며 점차 정상인 수준으로 증가하여 7일 이후에는 정상치에 도달하였다. Glutathione peroxidase의 활성도는 재생중인 간이나 정상인 개체의 간에서 별다른 차이가 없었다. 이것은 재생중인 간에서 재생초기에 cytochrome P-450의 함량과 NADPH-cytochrome c reductase의 활성도 감소가 lipid peroxidation과 약물 대사효소의 활성도 감소를 일으키며 이러한 현상은 부분 간 절제 후 7일 이후에는 거의 나타나지 않았다.