The Effect of Gingko Biloba Extract on Energy Metabolic Status in C3H Mouse Fibrosarcoma : Evaluated by in vivo $^{31}P$ Magnetic Resonance Spectroscopy

Gingko biloba extract가 C3H 마우스 섬유육종의 에너지 대사 상태에 미치는 영향 : 생체내 $^{31}P$ 자기공명 분광법을 이용한 분석

  • Ha Sung Whan (Department of Therapeutic Radiology, Laboratory of Radiation Biology, Cancer Research Center, Seoul National University, College of Medicine) ;
  • Kim Won Dong (Department of Therapeutic Radiology, Laboratory of Radiation Biology, Cancer Research Center, Seoul National University, College of Medicine) ;
  • Ahn Yong Chan (Department of Therapeutic Radiology, Laboratory of Radiation Biology, Cancer Research Center, Seoul National University, College of Medicine) ;
  • Park Chan Il (Department of Therapeutic Radiology, Laboratory of Radiation Biology, Cancer Research Center, Seoul National University, College of Medicine) ;
  • Lim Tae Hwan (NMR Division, Asan Institute for Life Sciences, Ulsan University) ;
  • Lee Tae Kuen (NMR Division, Asan Institute for Life Sciences, Ulsan University)
  • 하성환 (서울대학교 의과대학 치료방사선과학교실, 암연구소 방사선생물학연구실) ;
  • 김원동 (서울대학교 의과대학 치료방사선과학교실, 암연구소 방사선생물학연구실) ;
  • 안용찬 (서울대학교 의과대학 치료방사선과학교실, 암연구소 방사선생물학연구실) ;
  • 박찬일 (서울대학교 의과대학 치료방사선과학교실, 암연구소 방사선생물학연구실) ;
  • 임태환 (울산대학교 아산생명과학연구소, 자기공명분광연구실) ;
  • 이대근 (울산대학교 아산생명과학연구소, 자기공명분광연구실)
  • Published : 2002.06.01

Abstract

Purpose : Gingko biloba extract (GBE), a natural product extracted from Gingko leaves, is known to increase the radiosensitivity of tumors. This radiosensitization probably arises from the increase in the peripheral blood flow by decreasing the blood viscosity and relaxing the vasospasm. The influence of a GBE on the metabolic status in fibrosarcoma II (FSall) of a C3H mouse was investigated using $^{31}P$ magnetic resonance spectroscopy (MRS). Materials and Methods : Eighteen C3H mice with fibrosarcoma II $(from\;100\;mm^3\;to\;130\;mm^3)$ were prepared for this experiment. The mice were divided into 2 groups; one (9 mice) without a priming dose, and the other (9 mice) with a priming dose of GBE. The GBE priming dose (100 mg/kg) was administered by an intraperitoneal (i.p.) injection 24 hours prior to the measurement. First $^{31}P$ MRS spectra were measured in the mice from each group as a baseline and test dose of GBE (100 mg/kg) was then administered to each group. One hour later, the $^{31}P$ MRS spectra were measured again to evaluate the change in the energy metabolic status. Results : In the group without the priming dose, the mean pH, PCr/Pi, PME/ATP, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose were not changed significantly compared to the values at the baseline. However, in the group with the priming dose, the mean PCr/Pi, Pi/ATP, PCr/(Pi+PME) values 1 hour after the test dose changed from the baseline values of 0.49, 0.77, 0.17 to 0.74, 0.57, 0.28 respectively. According to the paired t-test, the differences were statistically significant. Conclusion : The above findings suggest that the metabolic status is significantly improved after administering GBE if the priming dose is given 24 hours earlier. This shows that the radiosensitizing effect of GBE is based on the increase of tumor blood flow and the improvement in the metabolic status.

목적 : 현재까지 방사선에 대한 저산소세포의 감수성을 높이기 위한 많은 실험적 및 임상적 연구가 진행되어 왔으나, 아직 적절한 방법이 개발되지 못한 상태이다. 본 연구에서는 혈관수축 이완 및 혈액점도 저하를 통하여 말초혈류 증가작용을 갖고 있는 Ginkgo biloba extract (GBE)가 종양내 대사상태에 어떠한 변화를 가져오는지를 $^{31}P$ 핵자기 공명 분광법을 통하여 알아보고자 하였다. 방법 : $100\;mm^3$에서 $130\;mm^3$의 섬유육종을 갖는 18마리의 C3H 마우스를 각각 9 마리씩 두 군으로 분리하였다. 한 군은 GBE로 전처치를 하지 않았으며 나머지 다른 한 군은 $^{31}P$ 자기공명분광법을 시행하기 24시간 전에 100 mg/kg의 GBE를 복강내로 투여하여 전처치를 하였다. 우선 각 군에서 $^{31}P$ 자기공명분광법을 실시하여 대조 spectrum을 얻었으며 그 후 100 mg/kg의 GBE를 재투여 하고 약 1시간 후에 $^{31}P$ 자기공명분광법을 다시 실시하였다. 결과 : 전처치를 하지 않은 군에서는 GBE 투여 전의 평균 pH, PCr/Pi, PME/ATP, Pi/ATP, PCr/(Pi+PME) 수치를 GBE 투여 후 1시간에 측정한 값과 비교하였을 때 통계학적인 차이가 없었다. 그러나 전처치를 한 군에서는 GBE 투여 전의 평균 PCr/Pi, Pi/ATP, PCr/(Pi+PME)수치가 0.49, 0.77, 0.17에서 GBE 투여 후에는 0.74, 0.57, 0.28로 변화하였으며 이는 paired-t test상 통계학적으로 의미있는 차이였다. 결론 : 전처치를 한 군에서 GBE의 재투여로 대사상태가 현저히 호전되었으며 이는 간접적으로 GBE 에 의한 방사선감수성의 증가가 혈류 증가 및 이에 따른 대사상태 호전에 기인함을 나타낸다.

Keywords

References

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