Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5856084 | Regulatory Toxicology and Pharmacology | 2016 | 6 Pages |
Abstract
The aim of this study was to evaluate the embryo-fetal development toxicity of honokiol microemulsion. The drug was intravenously injected to pregnant SD rats at dose levels of 0, 200, 600 and 2000 μg/kg/day from day 6-15 of gestation. All the pregnant animals were observed for body weights and any abnormal changes and subjected to caesarean-section on gestation day (GD) 20; all fetuses obtained from caesarean-section were assessed by external inspection, visceral and skeletal examinations. No treatment-related external alterations as well as visceral and skeletal malformations were observed in honokiol microemulsion groups. There was no significant difference in the body weight gain of the pregnant rats, average number of corpora lutea, and the gravid uterus weight in the honokiol microemulsion groups compared with the vehicle control group. However, at a dose level of 2000 μg/kg/day, there was embryo-fetal developmental toxicity observed, including a decrease in the body length and tail length of fetuses. In conclusion, the no-observed-adverse-effect level (NOAEL) of honokiol microemulsion is 600 μg/kg/day, 75 times above the therapeutic dosage and it has embryo-fetal toxicity at a dose level of 2000 μg/kg/day, which is approximately 250 times above the therapeutic dosage.
Keywords
GLPMPTPNOAELNMDAnNOSAAALACLOAELPARPN-methyl-d-aspartic acidPSD95rt-PASprague Dawleymitochondria permeability transition poreAssociation for Assessment and Accreditation of Laboratory Animal CareGood Laboratory Practicegestation daySODneuronal nitric oxide synthaseRecombinant tissue plasminogen activatorICHno-observed-adverse-effect levelpostsynaptic density protein 95poly ADP-ribose polymeraseinternational conference on harmonization of technical requirements for registration of pharmaceuticals for human useReactive oxygen species
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Authors
Qianqian Zhang, Xiangfeng Ye, Lingzhi Wang, Bangjie Peng, Yingxue Zhang, Jie Bao, Wanfang Li, Jinfeng Wei, Aiping Wang, Hongtao Jin, Shizhong Chen,