• Arch Med Sci · Mar 2017

    The vitamin D analogue paricalcitol attenuates hepatic ischemia/reperfusion injury through down-regulation of Toll-like receptor 4 signaling in rats.

    • Min Sung Kim, Soyoung Lee, Namhee Jung, Kiho Lee, Jinwoo Choi, Sang-Hoon Kim, Jinhyun Jun, Won-Mee Lee, Yeonsoo Chang, and Donghee Kim.
    • Department of Surgery, Eulji General Hospital, Eulji University School of Medicine, Seoul, Korea.
    • Arch Med Sci. 2017 Mar 1; 13 (2): 459-469.

    IntroductionRecent 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.Material And MethodsTwenty-four male Wistar rats were randomized into four groups: Saline + Sham, Saline + I/R, Paricalcitol + Sham, and Paricalcitol + I/R. A synthetic vitamin D2 analogue, 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.ResultsLiver 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.ConclusionsThe 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.

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