title: Peritoneal inflammation in pigs is associated with early mitochondrial dysfunction in liver and kidney.
abstract: The objective of this study was to investigate early effects of peritoneal inflammation on the mitochondrial function in the vital organs, liver and kidney, and their relation to inflammatory and oxidative stress mediators. The study was performed on 14 domestic pigs. Peritoneal inflammation was induced in anesthetized pigs after a midline laparotomy by autologous feces. Fluid resuscitation maintained a MAP above 60 mmHg. Animals were sacrificed 12 h later, and tissue samples were obtained to determine mitochondrial function, mRNA levels of relevant genes [inducible NO synthase (iNOS), inducible HO (HO-1), tumor necrosis factor-alpha (TNF-alpha)], generation of reactive oxygen species (ROS), and HO-1 activity. We found impaired mitochondrial function in both liver and kidney, based on decreased state 3 respiration in the liver and increased states 2 and 4 respiration in the kidney at 12 h. This was accompanied by increased TNF-alpha protein in the blood and up-regulation of TNF-alpha mRNA in the liver. Free iron was elevated in the liver but not in the kidney. In the kidney, mitochondrial ROS production was increased. Nitric oxide levels in blood remained unchanged, corresponding to unchanged levels of iNOS mRNA expression in liver and kidney. Similarly, HO-1 mRNA and heme oxygenase (HO)-activity were unchanged. The inflammatory response in the absence of characteristic septic symptoms was not associated with morphological organ damage at this early time point. Peritoneal inflammation in pigs caused mitochondrial dysfunction in liver and kidney, preceding signs of organ damage. We did not find proof that mitochondrial dysfunction was due to increased levels of either nitric oxide (NO) or products of HO, but it was accompanied by increased levels of oxidative stress markers.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, AUVA Research Center, 1200, Vienna, Austria. Andrey.Kozlov@trauma.lbg.ac.at
authors.forename: Andrey V
authors.initials: AV
authors.lastname: Kozlov
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.forename: Susanne
authors.initials: S
authors.lastname: Haindl
authors.forename: Ingeborg
authors.initials: I
authors.lastname: Kehrer
authors.forename: J Catharina
authors.initials: JC
authors.lastname: Duvigneau
authors.forename: Romana T
authors.initials: RT
authors.lastname: Hartl
authors.forename: Thomas
authors.initials: T
authors.lastname: Ebel
authors.forename: Mohammad
authors.initials: M
authors.lastname: Jafarmadar
authors.forename: Enrico
authors.initials: E
authors.lastname: Calzia
authors.forename: Erich
authors.initials: E
authors.lastname: Gnaiger
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Soheyl
authors.initials: S
authors.lastname: Bahrami
mesh_terms: D000818:Animals; D019069:Cell Respiration; D004195:Disease Models, Animal; D005260:Female; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006439:Hemodynamics; D018836:Inflammation Mediators / Q000378:metabolism*; D007501:Iron / Q000378:metabolism; D007668:Kidney / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000276:immunology / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics; D018384:Oxidative Stress / Q000235:genetics; D010538:Peritonitis / Q000235:genetics / Q000276:immunology / Q000378:metabolism* / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D034421:Sus scrofa; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D018836:Inflammation Mediators; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D009569:Nitric Oxide; D007501:Iron; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1