title: The vitamin D analogue paricalcitol attenuates hepatic ischemia/reperfusion injury through down-regulation of Toll-like receptor 4 signaling in rats.
abstract: BACKGROUND
  Recent studies have revealed that vitamin D and its synthetic analogues have a protective effect on experimental ischemia/reperfusion (I/R) models in several organs, but little is known about its effect on the liver. The aim of this study was to evaluate the beneficial effects of vitamin D in a model of liver I/R in rats, focusing on Toll-like receptor (TLR) 4 signaling, which has been shown to be involved in I/R injury.
  
  
  METHODS
  Twenty-four male Wistar rats were randomized into four groups: Saline + Sham, Saline + I/R, Paricalcitol + Sham, and Paricalcitol + I/R. A synthetic vitamin D2analogue, paricalcitol, was intraperitoneally injected 24 h prior to surgery. The animals were subjected to 60 min of partial warm ischemia (70%), followed by reperfusion for 6 h on the same day. The ischemic lobe of the liver and blood were collected for molecular biochemical analyses.
  
  
  RESULTS
  Liver damage following I/R was diminished by pretreatment with paricalcitol. Pretreatment with paricalcitol decreased the levels of pro-inflammatory mediators, such as interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and macrophage migration inhibitory factor (MIF), in both plasma and liver tissue. In addition, pretreatment with paricalcitol markedly down-regulated the expression of TLR4, HMGB1, TNF-α and NF-κB.
  
  
  CONCLUSIONS
  The vitamin D analogue paricalcitol attenuates hepatic I/R injury through down-regulation of the TLR4 signaling pathway and might be considered to be a potential nutritional therapeutic agent against I/R injury in the liver.
authors.affiliation: Department of Surgery, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Min Sung
authors.initials: MS
authors.lastname: Kim
authors.affiliation: Department of Nephrology, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Soyoung
authors.initials: S
authors.lastname: Lee
authors.affiliation: Eulji Medi-Bio Research Institute, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Namhee
authors.initials: N
authors.lastname: Jung
authors.affiliation: Department of Molecular Biology, Eulji University School of Medicine, Daecheon, Korea.
authors.forename: Kiho
authors.initials: K
authors.lastname: Lee
authors.affiliation: Eulji Medi-Bio Research Institute, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Jinwoo
authors.initials: J
authors.lastname: Choi
authors.affiliation: Eulji Medi-Bio Research Institute, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Sang-Hoon
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Eulji Medi-Bio Research Institute, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Jinhyun
authors.initials: J
authors.lastname: Jun
authors.affiliation: Eulji Medi-Bio Research Institute, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Won-Mee
authors.initials: WM
authors.lastname: Lee
authors.affiliation: Department of Surgery, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Yeonsoo
authors.initials: Y
authors.lastname: Chang
authors.affiliation: Department of Surgery, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
authors.forename: Donghee
authors.initials: D
authors.lastname: Kim
keywords: Toll-like receptor 4; hepatic ischemia/reperfusion injury; vitamin D