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INFLAMMATION/IMMUNITY/MEDIATORS
1Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Research Center of Allgemeine Unfallversicherungsansalt, and 2Research Institute of Biochemical Pharmacology and Toxicology, University of Veterinary Medicine, Vienna, Austria
Submitted 18 July 2005 ; accepted in final form 31 October 2005
This study was designed to clarify whether mitochondrial function/dysfunction and reactive oxygen species (ROS) production have a temporal relationship with organ failure during endotoxic shock. Adult male Sprague-Dawley rats were divided into three groups receiving 1) isotonic saline (control group, n = 16); 2) 8 mg/kg lipopolysaccharide (LPS; n = 8); or 3) 20 mg/kg LPS (n = 8) intraperitoneally under short anesthesia with 3.5% of isoflurane. After 16 h, animals were killed to analyze plasma, rat liver mitochondria (RLM), and rat heart mitochondria (RHM). In accordance with plasma analysis, LPS-treated rats were divided into "responders" and "nonresponders" with high and low levels of alanine aminotransferase and creatine, respectively. RHM from responders had significantly lower respiratory activity in state 3, suggesting a decreased rate of ATP synthesis. In contrast, RLM from responders had significantly higher respiratory activity in state 3 than both nonresponders and the control group. This increase was accompanied by a decrease in phosphate-to-oxygen ratio values, which was not observed in RHM. ROS generation determined with a spin probe, 1-hydroxy-3-carboxypyrrolidine, neither revealed a difference in RHM between LPS and control groups nor between responders and nonresponders. In contrast, RLM isolated from responders showed a marked increase in ROS production compared with both the control group and nonresponders. Our data demonstrate that 1) RHM and RLM respond to endotoxic shock in a different manner, decreasing and increasing respiratory activity, respectively, and 2) there is a temporal relationship between ROS production in RLM (but not in RHM) and tissue damage in rats subjected to LPS shock.
lipopolysaccharide; reactive oxygen species; organ failure; electron paramagnetic resonance; spin trap
This article has been cited by other articles:
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A. Dyson, R. Stidwill, V. Taylor, and M. Singer Tissue oxygen monitoring in rodent models of shock Am J Physiol Heart Circ Physiol, July 1, 2007; 293(1): H526 - H533. [Abstract] [Full Text] [PDF] |
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