PMID- 23760194
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20130614
LR  - 20211021
IS  - 1664-042X (Print)
IS  - 1664-042X (Electronic)
IS  - 1664-042X (Linking)
VI  - 4
DP  - 2013
TI  - Experimental data suggesting that inflammation mediated rat liver mitochondrial 
      dysfunction results from secondary hypoxia rather than from direct effects of 
      inflammatory mediators.
PG  - 138
LID - 10.3389/fphys.2013.00138 [doi]
LID - 138
AB  - Systemic inflammatory response (SIR) comprises both direct effects of 
      inflammatory mediators (IM) and indirect effects, such as secondary circulatory 
      failure which results in tissue hypoxia (HOX). These two key components, SIR and 
      HOX, cause multiple organ failure (MOF). Since HOX and IM occur and interact 
      simultaneously in vivo, it is difficult to clarify their individual pathological 
      impact. To eliminate this interaction, precision cut liver slices (PCLS) were 
      used in this study aiming to dissect the effects of HOX and IM on mitochondrial 
      function, integrity of cellular membrane, and the expression of genes associated 
      with inflammation. HOX was induced by incubating PCLS or rat liver mitochondria 
      at pO2 < 1% followed by reoxygenation (HOX/ROX model). Inflammatory injury was 
      stimulated by incubating PCLS with IM (IM model). We found upregulation of 
      inducible nitric oxide synthase (iNOS) expression only in the IM model, while 
      heme oxygenase 1 (HO-1) expression was upregulated only in the HOX/ROX model. 
      Elevated expression of interleukin 6 (IL-6) was found in both models reflecting 
      converging pathways regulating the expression of this gene. Both models caused 
      damage to hepatocytes resulting in the release of alanine aminotransferase (ALT). 
      The leakage of aspartate aminotransferase (AST) was observed only during the 
      hypoxic phase in the HOX/ROX model. The ROX phase of HOX, but not IM, drastically 
      impaired mitochondrial electron supply via complex I and II. Additional 
      experiments performed with isolated mitochondria showed that free iron, released 
      during HOX, is likely a key prerequisite of mitochondrial dysfunction induced 
      during the ROX phase. Our data suggests that mitochondrial dysfunction, 
      previously observed in in vivo SIR-models, is the result of secondary circulatory 
      failure inducing HOX rather than the result of a direct interaction of IM with 
      liver cells.
FAU - Weidinger, Adelheid
AU  - Weidinger A
AD  - Ludwig Boltzmann Institute for Experimental and Clinical Traumatology Vienna, 
      Austria.
FAU - Dungel, Peter
AU  - Dungel P
FAU - Perlinger, Martin
AU  - Perlinger M
FAU - Singer, Katharina
AU  - Singer K
FAU - Ghebes, Corina
AU  - Ghebes C
FAU - Duvigneau, J Catharina
AU  - Duvigneau JC
FAU - Mullebner, Andrea
AU  - Mullebner A
FAU - Schafer, Ute
AU  - Schafer U
FAU - Redl, Heinz
AU  - Redl H
FAU - Kozlov, Andrey V
AU  - Kozlov AV
LA  - eng
PT  - Journal Article
DEP - 20130607
PL  - Switzerland
TA  - Front Physiol
JT  - Frontiers in physiology
JID - 101549006
PMC - PMC3675332
OTO - NOTNLM
OT  - HO-1
OT  - IL-6
OT  - cytokine
OT  - free iron
OT  - iNOS
OT  - lipopolysaccharide
OT  - liver
OT  - reoxygenation
EDAT- 2013/06/14 06:00
MHDA- 2013/06/14 06:01
PMCR- 2013/06/07
CRDT- 2013/06/14 06:00
PHST- 2013/02/22 00:00 [received]
PHST- 2013/05/22 00:00 [accepted]
PHST- 2013/06/14 06:00 [entrez]
PHST- 2013/06/14 06:00 [pubmed]
PHST- 2013/06/14 06:01 [medline]
PHST- 2013/06/07 00:00 [pmc-release]
AID - 10.3389/fphys.2013.00138 [doi]
PST - epublish
SO  - Front Physiol. 2013 Jun 7;4:138. doi: 10.3389/fphys.2013.00138. eCollection 2013.