Ryu J C, Kim K R, Kim H J, Youn J Y, Myung S W, Kim G H, Lee M J, Chang I M
Toxicology Laboratory, Korea Institute of Science and Technology, Seoul, Korea.
Arch Pharm Res. 1998 Aug;21(4):391-7. doi: 10.1007/BF02974632.
The toxicity evaluation of oriental herbal drugs is of great concern at present. Bojungchisuptang (BCST, in Korean), a decocted medicine of oriental herbal mixture, is now well used in clinic at oriental hospitals for the treatment of edema of several diseases in practice. However, the toxicity of the oriental herbal decocted medicines such as genetic toxicity is not well defined until now. In this respect, to clarify the genetic toxicity of BCST, in vitro chromosome aberration assay with Chinese hamster lung (CHL) fibroblasts and in vivo supravital micronucleus assay with mouse peripheral reticulocytes were performed in this study. In the chromosome aberration assay, we used 5,000 micrograms/ml BCST as maximum concentration because no remarkable cytotoxicity in CHL cells was observed both in the presence and absence of S-9 metabolic activation system. No statistical significant differences of chromosome aberrations were observed in CHL cells treated with 5,000, 2,500 and 1,250 micrograms/ml BCST for 6 hour both in the presence and absence of S-9 metabolic activation. However, very weak positive result (6.5-8.0% aberration) of BCST was obtained in the absence of S-9 metabolic activation system at 5,000 micrograms/ml BCST when treated for 24 hour, i.e. 1.5 normal cell cycle time. And also, in vivo clastogenicity of BCST was studied by acridine orange-supravital staining micronucleus assay using mouse peripheral reticulocytes. We used 2,000 mg/kg as the highest oral dose in this micronucleus assay because no acute oral toxicity of BCST was observed in mice. The optimum induction time of micronucleated reticulocytes (MNRETs) was determined as 36 hours after oral administration of 2,000 mg/kg BCST. No significant differences of MNRETs between control and BCST treatment groups were observed in vivo micronucleus assay. From these results, BCST revealed very weak positive result in chromosome aberration assay in vitro with CHL cells and no clastogenicity in micronucleus assay in vivo.
目前,东方草药的毒性评估备受关注。补中益气汤(韩语:Bojungchisuptang,简称BCST)是一种东方草药混合煎剂,目前在东方医院临床中广泛用于治疗多种疾病引起的水肿。然而,直到现在,像遗传毒性这样的东方草药煎剂的毒性仍未明确界定。在这方面,为了阐明BCST的遗传毒性,本研究采用中国仓鼠肺(CHL)成纤维细胞进行体外染色体畸变试验,并采用小鼠外周网织红细胞进行体内活体微核试验。在染色体畸变试验中,我们将5000微克/毫升的BCST作为最大浓度,因为在有和没有S-9代谢激活系统的情况下,CHL细胞中均未观察到明显的细胞毒性。在有和没有S-9代谢激活的情况下,用5000、2500和1250微克/毫升的BCST处理CHL细胞6小时,未观察到染色体畸变的统计学显著差异。然而,当在无S-9代谢激活系统的情况下,用5000微克/毫升的BCST处理24小时(即1.5个正常细胞周期时间)时,获得了BCST非常微弱的阳性结果(畸变率为6.5 - 8.0%)。此外,通过使用小鼠外周网织红细胞的吖啶橙活体染色微核试验研究了BCST的体内致断裂性。在该微核试验中,我们将2000毫克/千克作为最高口服剂量,因为在小鼠中未观察到BCST的急性口服毒性。微核网织红细胞(MNRETs)的最佳诱导时间确定为口服2000毫克/千克BCST后36小时。在体内微核试验中,未观察到对照组和BCST处理组之间MNRETs的显著差异。从这些结果来看,BCST在体外CHL细胞染色体畸变试验中显示出非常微弱的阳性结果,在体内微核试验中无致断裂性。