title: Pitavastatin ameliorated the progression of steatohepatitis in ovariectomized mice fed a high fat and high cholesterol diet.
abstract: OBJECTIVE
  Many studies indicate an accelerated progression of non-alcoholic steatohepatitis (NASH) in postmenopausal women. Very recently, we reported that estrogen deficiency enhanced the progression of steatohepatitis in mice fed a high fat and high cholesterol (HFHC) diet. Hypercholesterolemia is often observed in postmenopausal women, and recent studies indicate it to be an important risk factor for the progression of NASH. Statins can slow NASH progression in the estrogen-deficient state but the precise mechanisms of their effects are still unclear.
  
  
  METHODS
  We investigated the effects of pitavastatin on steatohepatitis progression using ovariectomized (OVX) mice fed a HFHC diet or HFHC + pitava diet (containing 5 p.p.m. pitavastatin) for 6 weeks.
  
  
  RESULTS
  Serum alanine aminotransferase and cholesterol levels significantly decreased in mice fed the HFHC + pitava diet compared with mice fed the HFHC diet. Real-time reverse transcription polymerase chain reaction representing hepatic inflammatory gene expressions significantly decreased in mice fed the HFHC + pitava diet compared with the HFHC-fed mice. Pitavastatin treatment also decreased both hepatic macrophage infiltration and hepatocyte chemokine (C-C motif) ligand 2 expression and improved the liver fibrosis condition when compared with the mice fed the HFHC diet. In addition, the enhanced spleen monocyte chemokine (C-C motif) receptor 2 expression in ovariectomized mice fed the HFHC diet was also decreased by pitavastatin administration.
  
  
  CONCLUSIONS
  Our study demonstrated that the exacerbated steatohepatitis progression in OVX mice fed a HFHC diet could be attenuated by pitavastatin treatment at least through inhibition of hepatic macrophage infiltration. We concluded that statins should be useful for treating NASH in postmenopausal women.
authors.affiliation: Department of Gastroenterology and Hepatology; Molecular Biochemistry and Clinical Investigation, Osaka University, Graduate School of Medicine, Osaka.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kamada
authors.forename: Shinichi
authors.initials: S
authors.lastname: Kiso
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yoshida
authors.forename: Norihiro
authors.initials: N
authors.lastname: Chatani
authors.forename: Takashi
authors.initials: T
authors.lastname: Kizu
authors.forename: Mina
authors.initials: M
authors.lastname: Hamano
authors.forename: Mayumi
authors.initials: M
authors.lastname: Egawa
authors.forename: Takayo
authors.initials: T
authors.lastname: Takemura
authors.forename: Hisao
authors.initials: H
authors.lastname: Ezaki
authors.forename: Kunimaro
authors.initials: K
authors.lastname: Furuta
authors.forename: Norio
authors.initials: N
authors.lastname: Hayashi
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Takehara