title: Importance of detoxifying enzymes in differentiating fibrotic development between SHRSP5/Dmcr and SHRSP rats.
abstract: OBJECTIVE
  High-fat and -cholesterol diet (HFC) induced fibrotic steatohepatitis in stroke-prone spontaneously hypertensive rat (SHRSP) 5/Dmcr, the fifth substrain from SHRSP, by dysregulating bile acid (BA) kinetics. This study aimed to clarify the histopathological and BA kinetic differences in HFC-induced fibrosis between SHRSP5/Dmcr and SHRSP.
  
  
  METHODS
  Ten-week-old male SHRSP5/Dmcr and SHRSP were randomly allocated to groups and fed with either control diet or HFC for 2 and 8 weeks. The liver histopathology, biochemical features, and molecular signaling involved in BA kinetics were measured.
  
  
  RESULTS
  HFC caused more severe hepatocyte ballooning, macrovesicular steatosis and fibrosis in SHRSP5/Dmcr than in SHRSP. It was noted that fibrosis was disproportionately formed in retroperitoneal side of both strains. As for BA kinetics, HFC greatly increased the level of Cyp7a1 and Cyp7b1 to the same degree in both strains at 8 weeks, while multidrug resistance-associated protein 3 was greater in SHRSP5/Dmcr than SHRSP. The diet decreased the level of bile salt export pump by the same degree in both strains, while constitutive androstane receptor, pregnane X receptor, and UDP-glucuronosyltransferase activity more prominent in SHRSP5/Dmcr than SHRSP at 8 weeks. In the fibrosis-related genes, only expression of collagen, type I, alpha 1 mRNA was greater in SHRSP5/Dmcr than SHRSP.
  
  
  CONCLUSIONS
  The greater progression of fibrosis in SHRSP5/Dmcr induced by HFC may be due to greater suppression of UDP-glucuronosyltransferase activity detoxifying toxicants, such as hydrophobic BAs.
authors.affiliation: Department of Public Health, Fujita Health University School of Medicine, Dengakugakubo 1-98, Kutsukake-cho, Toyoake, 470-1192, Japan. naitoh@med.nagoya-u.ac.jp.|Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan. naitoh@med.nagoya-u.ac.jp.
authors.forename: Hisao
authors.initials: H
authors.lastname: Naito
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Jia
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Husna
authors.initials: H
authors.lastname: Yetti
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yukie
authors.initials: Y
authors.lastname: Yanagiba
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.|College of Human Life and Environment, Kinjo Gakuin University, Nagoya, Japan.
authors.forename: Hazuki
authors.initials: H
authors.lastname: Tamada
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.|College of Human Life and Environment, Kinjo Gakuin University, Nagoya, Japan.
authors.forename: Kazuya
authors.initials: K
authors.lastname: Kitamori
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yumi
authors.initials: Y
authors.lastname: Hayashi
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Kato
authors.affiliation: Department of Legal Medicine and Bioethics, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Department of Occupational and Environmental Health, Nagoya University Graduate School of Medicine, Nagoya, Japan.|College of Life and Health Sciences, Chubu University, Kasugai, Japan.
authors.forename: Tamie
authors.initials: T
authors.lastname: Nakajima
mesh_terms: D000818:Animals; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects*; D018450:Disease Progression; D005234:Fatty Liver / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D005355:Fibrosis; D008658:Inactivation, Metabolic; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008297:Male; D011897:Random Allocation; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D002791:Cholesterol, Dietary
keywords: Bile acid; Constitutive androstane receptor; Pregnane X receptor; Resistance-associated protein 3; UDP-glucuronosyltransferase activity