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

Autor: Wei Li, Yu-Qing Zhao, Yaoxian Xuan, Yanfei Xin, Xiangrong Zhang, Meng Ding
Rok vydání: 2019
Předmět:
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
Zdroj: Journal of Ginseng Research, Vol 43, Iss 4, Pp 562-571 (2019)
Journal of Ginseng Research
ISSN: 1226-8453
DOI: 10.1016/j.jgr.2018.05.005
Popis: 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
Databáze: OpenAIRE
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