title: Thirty-day rat toxicity study reveals reversible liver toxicity of mifepristone (RU486) and metapristone.
abstract: OBJECTIVE
  Mifepristone (RU486) is an oral first-line contraceptive used by hundreds of millions of women, and recently it was tested for anticancer activity in both genders worldwide. We are developing metapristone (the N-monodemethyl RU486) as a potential metastasis chemopreventive. The present acute and 30-d subacute toxicity study aimed at examining and compared in parallel the potential toxicity of the two drugs.
  
  
  METHODS
  The single-dose acute toxicity and 30-d subacute toxicity studies were conducted in mice and rats, respectively, by gavaging metapristone or mifepristone at various doses. Blood samples and organs were collected for blood chemistry, hematology and histology analyses.
  
  
  RESULTS
  Oral mifepristone (3000 mg/kg) caused 30% and 40% death in female and male mice, respectively, within 15 h post-dosing. In comparison, the same dose of metapristone produced 30% acute death in males only. Thirty-day oral administration of the two drugs to rats (12.5, 50 and 200 mg/kg/day) caused reversible hepatotoxicity that only occurred at 200 mg/kg/day group, evidenced by the elevated liver enzyme activity and liver organ weight.
  
  
  CONCLUSIONS
  The present study, for the first time, reveals reversible hepatotoxicity in rats caused by the 30-d consecutive administration at the high dose, and warns the potential hepatotoxicity caused by long-term administrations of high doses of mifepristone or metapristone in clinical trials but not by the acute single abortion doses.
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Yingying
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Yewei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Suhong
authors.initials: S
authors.lastname: Yu
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Cuicui
authors.initials: C
authors.lastname: Yan
authors.affiliation: b Department of Pharmaceutics , University of Washington , Seattle , WA , USA , and.
authors.forename: Rodney J  Y
authors.initials: RJ
authors.lastname: Ho
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Liyuan
authors.initials: L
authors.lastname: Wan
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Xingtian
authors.initials: X
authors.lastname: Yang
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Huo
authors.initials: H
authors.lastname: Xu
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Jichuang
authors.initials: J
authors.lastname: Wang
authors.affiliation: c Surgery Department, Fuzhou General Hospital , Fuzhou , China.
authors.forename: Xiaohuang
authors.initials: X
authors.lastname: Tu
authors.affiliation: a Cancer Metastasis Alert and Prevention Center, and Pharmaceutical Photocatalysis of State Key Laboratory of Photocatalysis on Energy and Environment, College of Chemistry, Fuzhou University , Fuzhou , China .
authors.forename: Lee
authors.initials: L
authors.lastname: Jia
mesh_terms: D000021:Abortifacient Agents, Steroidal / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000473:pathology*; D005260:Female; D008297:Male; D015735:Mifepristone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000633:toxicity*; D051381:Rats
chemical_list: D000021:Abortifacient Agents, Steroidal; D015735:Mifepristone; C000592521:metapristone
keywords: Acute toxicity; liver toxicity; metapristone; mifepristone; subacute toxicity