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Embryo-fetal development toxicity of honokiol microemulsion intravenously administered to pregnant rats |
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| Affiliation: | 2. Department of Experimental Medicine, Second University of Naples, Naples, Italy;3. Department of Clinical and Experimental Medicine, Second University of Naples, Naples, Italy |
| 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: | Honokiol microemulsion Cerebral ischemia protection Embryo-fetal development toxicity AAALAC"} {"#name":"keyword" "$":{"id":"kwrd0030"} "$$":[{"#name":"text" "_":"Association for Assessment and Accreditation of Laboratory Animal Care GD"} {"#name":"keyword" "$":{"id":"kwrd0040"} "$$":[{"#name":"text" "_":"gestation day GLP"} {"#name":"keyword" "$":{"id":"kwrd0050"} "$$":[{"#name":"text" "_":"Good Laboratory Practice ICH"} {"#name":"keyword" "$":{"id":"kwrd0060"} "$$":[{"#name":"text" "_":"International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use LOAEL"} {"#name":"keyword" "$":{"id":"kwrd0070"} "$$":[{"#name":"text" "_":"lowest-observed–adverse-effect level MPTP"} {"#name":"keyword" "$":{"id":"kwrd0080"} "$$":[{"#name":"text" "_":"mitochondria permeability transition pore NMDA"} {"#name":"keyword" "$":{"id":"kwrd0090"} "$$":[{"#name":"text" "$$":[{"#name":"__text__" "_":"N-methyl-"} {"#name":"small-caps" "_":"d"} {"#name":"__text__" "_":"-aspartic acid nNOS"} {"#name":"keyword" "$":{"id":"kwrd0100"} "$$":[{"#name":"text" "_":"neuronal nitric oxide synthase NOAEL"} {"#name":"keyword" "$":{"id":"kwrd0110"} "$$":[{"#name":"text" "_":"no-observed-adverse-effect level PARP"} {"#name":"keyword" "$":{"id":"kwrd0120"} "$$":[{"#name":"text" "_":"poly ADP-ribose polymerase PSD95"} {"#name":"keyword" "$":{"id":"kwrd0130"} "$$":[{"#name":"text" "_":"postsynaptic density protein 95 rt-PA"} {"#name":"keyword" "$":{"id":"kwrd0140"} "$$":[{"#name":"text" "_":"recombinant tissue plasminogen activator SD"} {"#name":"keyword" "$":{"id":"kwrd0150"} "$$":[{"#name":"text" "_":"Sprague Dawley SOD"} {"#name":"keyword" "$":{"id":"kwrd0160"} "$$":[{"#name":"text" "_":"reactive oxygen species |
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