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01 October 2011

Rosiglitazone protects against severe hemorrhagic shock-induced organ damage in rats

Fwu-Lin YangAE, Yi-Maun SubeqB, Chung-Jen LeeB, Ru-Ping LeeC, Tai-Chu PengB, Horng-Jyh HarnC, Bang-Gee HsuAEF

DOI: 10.12659/MSM.881975

Med Sci Monit 2011; 17(10): BR282-289

Abstract

Background: Hemorrhagic shock (HS) followed by resuscitation can induce the production of several inflammatory mediators and lead to multiple organ dysfunction. The molecular mechanism of biologic responses to rosiglitazone has an anti-inflammatory effect. The present study was designed to investigate the effects of rosiglitazone on physiopathology and inflammatory mediators after HS in rats.
Material/Methods: HS was induced in rats by withdrawing 60% of the total blood volume from a femoral artery catheter, immediately followed by intravenous injection of 0.3 mg/kg rosiglitazone. Mean arterial pressure (MAP) and heart rate (HR) were monitored continuously for 12 h. Levels of biochemical parameters, including GOT, GPT, BUN, Cre, LDH, CPK, and lactate were measured at 30 min before induction of HS and 0, 1, 3, 6, 9, and 12 h after HS, while an equal volume of normal saline was replaced as fluid resuscitation. Inflammatory mediators, including tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), were measured in serum at 1 and 12 h after HS. The kidneys, liver, lungs, and small intestine were removed for histological assessment by hematoxylin and eosin stained at 48 h after HS.
Results: HS significantly increased blood GOT, GPT, BUN, Cre, LDH, CPK, lactate, glucose, TNF-alpha, IL-6 and MCP-1 levels, induced tachycardia, and decreased mean arterial pressure (MAP) in rats. Treatment with rosiglitazone improved survival rate, decreased the markers of organ injury, and suppressed the release of TNF-alpha, IL-6, and MCP-1 after HS in rats.
Conclusions: Treatment with rosiglitazone suppresses the release of serum TNF-alpha, IL-6 and MCP-1, and ameliorates HS-induced organ damage in rats.

Keywords: Rats, Wistar, Shock, Hemorrhagic - complications, Multiple Organ Failure - prevention & control, Interleukin-6 - blood, Heart Rate, Enzyme-Linked Immunosorbent Assay, Chemokine CCL2 - blood, Blood Pressure, Blood Chemical Analysis, Anti-Inflammatory Agents - pharmacology, Survival Analysis, Thiazolidinediones - pharmacology, Tumor Necrosis Factor-alpha - blood

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750