Abstract：
: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.
journal_name
Fitoterapiajournal_title
Fitoterapiaauthors
Tang S,Ma X,Lu J,Zhang Y,Liu M,Wang Xdoi
10.1016/j.fitote.2019.04.016subject
Has Abstractpub_date
2019-07-01 00:00:00pages
104161eissn
0367-326Xissn
1873-6971pii
S0367-326X(19)30609-4journal_volume
136pub_type
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