title: Calcitriol decreases pro-inflammatory cytokines and protects against severe hemorrhagic shock induced-organ damage in rats.
abstract: Resuscitation after hemorrhagic shock (HS) could result in increased pro-inflammatory cytokines and then multiple organ dysfunctions. Calcitriol exerts pleiotropic effects in a wide variety of target tissues and has a role against anti-inflammation. The present study was aimed to investigate the modulatory effects of calcitriol on the pathophysiological and inflammatory markers following HS in rats.
  
  
  
  By withdrawing 60% of the total blood volume over 30min via a femoral artery catheter in rats, HS was induced. Afterwards, 10ng/kg calcitriol was injected intravenously in rats. After performing these procedures, hemodynamic status of mean arterial pressure (MAP) and heart rate (HR) were continuously monitored for 12h. Hemoglobin, lactic dehydrogenase (LDH), creatine phosphokinase (CPK), liver and renal function were measured at 30min before the induction of HS and 0, 1, 3, 6, 9, and 12h after HS, while an equal volume of normal saline as replacement fluid. At 1 and 12h after inducing HS, serum levels of tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) levels were measured, and the livers, kidneys and lungs were taken out and then examined histo-pathologically at 48h after inducing HS.
  
  
  
  Hemoglobin and MAP were significantly decreased, liver and renal function were significantly impaired, but HR and the levels of LDH, CPK, TNF-α and IL-6 were significantly increased after HS in rats. After being treated with calcitriol following HS resulted in better survival rate, lower serum levels of TNF-α and IL-6, and lesser hepatic, renal, and pulmonary histo-pathologic scores of injury in rats.
  
  
  
  Being treated with calcitriol after HS could ameliorate the pro-inflammatory reactions by modulating the effects of cytokines, which lead to prevention of subsequent major organ damages.
authors.affiliation: Division of Nephrology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan.
authors.forename: Jen-Pi
authors.initials: JP
authors.lastname: Tsai
authors.affiliation: Department of Nursing, Tzu Chi University of Science and Technology, Hualien, Taiwan.
authors.forename: Chung-Jen
authors.initials: CJ
authors.lastname: Lee
authors.affiliation: Department of Nursing, Tzu Chi University, Hualien, Taiwan.
authors.forename: Yi-Maun
authors.initials: YM
authors.lastname: Subeq
authors.affiliation: Institute of Medical Sciences, Tzu Chi University, Hualien, Taiwan.
authors.forename: Ru-Ping
authors.initials: RP
authors.lastname: Lee
authors.affiliation: School of Medicine, Tzu Chi University, Hualien, Taiwan; Division of Nephrology, Tzu Chi General Hospital, Hualien, Taiwan. Electronic address: gee.lily@msa.hinet.net.
authors.forename: Bang-Gee
authors.initials: BG
authors.lastname: Hsu
mesh_terms: D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D003402:Creatine Kinase / Q000097:blood; D015850:Interleukin-6 / Q000097:blood*; D007770:L-Lactate Dehydrogenase / Q000097:blood; D008297:Male; D009102:Multiple Organ Failure / Q000097:blood / Q000188:drug therapy; D051381:Rats; D011921:Rats, Inbred WKY; D012771:Shock, Hemorrhagic / Q000097:blood / Q000188:drug therapy; D014409:Tumor Necrosis Factor-alpha / Q000097:blood*
chemical_list: D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D007770:L-Lactate Dehydrogenase; D003402:Creatine Kinase; D002117:Calcitriol
keywords: Calcitriol; Cytokine; Hemorrhagic shock; Interleukin-6; Tumor necrosis factor-α