Journal
FITOTERAPIA
Volume 136, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.fitote.2019.04.016
Keywords
Ailanthone; Acute toxicity; Subacute toxicity; Toxicokinetics; Prostate cancer
Categories
Funding
- National Natural Science Foundation of China [81773808, 81830083]
- Science and Technology Commission of Shanghai Municipality [17140901000, 17140901001, 18430760400]
- Innovation Program of Shanghai Municipal Education Commission [2017-01-07-00-05-E00011]
- ECNU Public Platform for Innovation [011]
Ask authors/readers for more resources
Ailanthone (AIL) has many biological activities including antimalarial, antiviral and anticancer. Our previous study also found that AIL targets p23 against castration-resistant prostate cancer. In this report, the preclinical safety of AIL was evaluated by acute toxicity, subacute toxicity and toxicokinetics in mice. In the acute toxicity study, the LD50 of AIL was 27.3 mg/kg, and severe pathological damages were mainly found in the liver and gastrointestinal tract. In the subacute toxicity study, mice were orally administered at doses of 2.5, 5 and 10 mg/kg for 28 days. The results showed the body weight of male mice in the 10 mg/kg dose group decreased, but that of female mice increased. Biochemical and histopathological analysis showed that AIL could cause steatohepatitis, splenomegaly, gastrointestinal mucosal damage and reproductive system abnormalities. In addition, AIL presented the reversible hematotoxicity. To determine the relationship between AIL toxicity and dose/exposure in vivo, toxicokinetics of AIL were carried out after a single oral dose of 15 mg/kg. The stomach was identified as the main target organ, followed by the intestine and kidney. On the basis of this study, the dose of 2.5 mg/kg had no adverse effect on mice. To sum up, this study is the first time to evaluate the systemic toxicity of AIL, which is useful for the further development of AIL.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available