1. Genotoxicity and subchronic toxicological study of a novel ginsenoside derivative 25-OCH3-PPD in beagle dogs
- Author
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Wei Li, Yu-Qing Zhao, Yaoxian Xuan, Yanfei Xin, Xiangrong Zhang, and Meng Ding
- Subjects
0301 basic medicine ,white blood cells count, WBC ,hemoglobin concentration distribution width, HDW ,glucose, GLU ,potassium, K ,hematocrit, HCT ,Pharmacology ,medicine.disease_cause ,Beagle ,total protein, T.P ,creatinine, Crea ,Ames test ,chemistry.chemical_compound ,25-OCH3-PPD, 25-methoxydammarane-3, 12, 20-triol ,0302 clinical medicine ,platelets, PLT ,creatine phosphokinase, CK ,lcsh:Botany ,Subchronic toxicity ,red cell distribution width, RDW% ,total bilirubin, T.BIL ,total triglyceride, TG ,Erythrocyte count, RBC ,prothrombin time, PT ,SPSS, statistical package for social sciences ,mean corpuscular hemoglobin, MCH ,polychromatic erythrocytes, PCE ,micronucleated polychromatic erythrocytes, MNPCE ,Beagle dog ,lcsh:QK1-989 ,urea nitrogen, BUN ,chloride, Cl ,Ginsenoside ,030220 oncology & carcinogenesis ,Micronucleus test ,Toxicity ,reticulocyte count, RETIC ,albumin, ALB ,hemoglobin concentration, HGB ,Research Article ,total calcium, TCa ,Biotechnology ,eosinophils, EOS ,neutrophil cell, NEUT ,alanine aminotransferase, ALT ,sodium, Na ,Biochemistry, Genetics and Molecular Biology (miscellaneous) ,basophils, BASO ,mean corpuscular hemoglobin concentration, MCHC ,03 medical and health sciences ,monocytes, MONO ,gamma-glutamyl transferase, γ-GT ,medicine ,Adverse effect ,aspartate aminotransferase, AST ,business.industry ,mean platelet volume, MPV ,lymphocytes, LYMPH ,alkaline phosphatase, ALP ,030104 developmental biology ,Complementary and alternative medicine ,chemistry ,normochromatic erythrocytes, NCE ,total cholesterol, T.CHO ,Micronucleus ,business ,Genotoxicity ,mean corpuscular volume, MCV - 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-OCH3-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-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 genotoxicity of 25-OCH3-PPD. Results: There was no 25-OCH3-PPD–induced systemic toxicity in beagle dogs at any doses. The level of 25-OCH3-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-OCH3-PPD administrated groups compared to the vehicle control group. There were also no significant differences between 25-OCH3-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-OCH3-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-OCH3-PPD is an extremely safe candidate compound for antitumor treatment. Keywords: Beagle dog, Subchronic toxicity, Ginsenoside
- Published
- 2019