Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH(3)-PPD in beagle dogs

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–induced 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.