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

• Main Authors: Min Sung Kim, Soyoung Lee, Namhee Jung, Kiho Lee, Jinwoo Choi, Sang-Hoon Kim, Jinhyun Jun, Won-Mee Lee, Yeonsoo Chang, Donghee Kim
• Format: Article
• Language: English
• Published: Termedia Publishing House 2016-06-01
• Series: Archives of Medical Science
• Subjects: hepatic ischemia/reperfusion injury; Toll-like receptor 4; vitamin D
• Online Access: https://www.termedia.pl/The-vitamin-D-analogue-paricalcitol-attenuates-hepatic-ischemia-reperfusion-injury-through-down-regulation-of-Toll-like-receptor-4-signaling-in-rats,19,27790,1,1.html

Introduction : 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. Material and 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 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. 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)-1, tumor necrosis factor (TNF)-, 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- and NF-B. 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.