Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs
Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs
Wei Li(Shenyang pharmaceutical University); Xiangrong Zhang(Shenyang pharmaceutical University); Meng Ding(Shenyang pharmaceutical University); Yanfei Xin(Zhejiang Academy of Medical Sciences,); Yaoxian Xuan(Zhejiang Academy of Medical Sciences,); Yuqing Zhao(Shenyang pharmaceutical University)
43권 4호, 562~571쪽
초록
Background: Ginsenosides have been widely used clinically for many years and were regarded as verysafe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosidesmay have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potentialtoxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of25-methoxydammarane-3, 12, 20-triol (25-OCH3-PPD), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedlyorally administered with 25-OCH3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicityof 25-OCH3-PPD. Results: There was no 25-OCH3-PPDeinduced systemic toxicity in beagle dogs at any doses. The level of25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result ofAmes test showed that there was no significant increase in the number of revertant colonies of 25-OCH3-PPD administrated groups compared to the vehicle control group. There were also no significant differencesbetween 25-OCH3-PPD administrated groups at all dose levels and negative group in themicronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of 25-OCH3-PPD at which no adverse effects were observed was foundto be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH3-PPD is an extremely safe candidate compound for antitumor treatment
Abstract
Background: Ginsenosides have been widely used clinically for many years and were regarded as verysafe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosidesmay have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potentialtoxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of25-methoxydammarane-3, 12, 20-triol (25-OCH3-PPD), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedlyorally administered with 25-OCH3-PPD capsule at 60, 120, and 240 mg/kg/day for 91 consecutive days. Ames, micronucleus, and chromosomal aberration tests were established to analyze the possible genotoxicityof 25-OCH3-PPD. Results: There was no 25-OCH3-PPDeinduced systemic toxicity in beagle dogs at any doses. The level of25-OCH3-PPD at which no adverse effects were observed was found to be 240 mg/kg/day. The result ofAmes test showed that there was no significant increase in the number of revertant colonies of 25-OCH3-PPD administrated groups compared to the vehicle control group. There were also no significant differencesbetween 25-OCH3-PPD administrated groups at all dose levels and negative group in themicronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of 25-OCH3-PPD at which no adverse effects were observed was foundto be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. 25-OCH3-PPD is an extremely safe candidate compound for antitumor treatment
- 발행기관:
- 고려인삼학회
- 분류:
- 기타의약학