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http://dx.doi.org/10.1016/j.jgr.2018.05.005

Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs  

Li, Wei (Department of Functional Food and Wine, Shenyang pharmaceutical University)
Zhang, Xiangrong (Department of Functional Food and Wine, Shenyang pharmaceutical University)
Ding, Meng (Department of Functional Food and Wine, Shenyang pharmaceutical University)
Xin, Yanfei (Center of Safety Evaluation, Zhejiang Academy of Medical Sciences)
Xuan, Yaoxian (Center of Safety Evaluation, Zhejiang Academy of Medical Sciences)
Zhao, Yuqing (Department of Functional Food and Wine, Shenyang pharmaceutical University)
Publication Information
Journal of Ginseng Research / v.43, no.4, 2019 , pp. 562-571 More about this Journal
Abstract
Background: Ginsenosides have been widely used clinically for many years and were regarded as very safe. However, a few researches on the toxicities of these kinds of agents showed that some ginsenosides may have side-effect on the rats or dogs. So it is extremely necessary to further clarify the potential toxicity of ginsenosides. This study was carried out to investigate long-term toxicity and genotoxicity of 25-methoxydammarane-3, 12, 20-triol ($25-OCH_3-PPD$), a new derivative of ginsenoside, in beagle dogs. Methods: Twenty-four beagle dogs were divided randomly into four treatment groups and repeatedly orally administered with $25-OCH_3-PPD$ 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 genotoxicity of $25-OCH_3-PPD$. Results: There was no $25-OCH_3-PPD$einduced systemic toxicity in beagle dogs at any doses. The level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg/day. The result of Ames test showed that there was no significant increase in the number of revertant colonies of $25-OCH_3-PPD$ administrated groups compared to the vehicle control group. There were also no significant differences between $25-OCH_3-PPD$ administrated groups at all dose levels and negative group in the micronucleus test and chromosomal aberration assay. Conclusion: The highest dose level of $25-OCH_3-PPD$ at which no adverse effects were observed was found to be 240 mg/kg per day, and it is not a genotoxic agent either in somatic cells or germs cells. $25-OCH_3-PPD$ is an extremely safe candidate compound for antitumor treatment.
Keywords
Beagle dog; Subchronic toxicity; Ginsenoside;
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