Remote ischemic preconditioning differentially affects NADPH oxidase isoforms during hepatic ischemia-reperfusion

Dénes Garab, Ngwi Fet, Andrea Szabó, René H. Tolba, M. Borós, Petra Hartmann

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Aims We investigated the function of major superoxide-generating enzymes after remote ischemic preconditioning (IPC) and hepatic ischemia-reperfusion (IR), with the specific aim of assessing the importance of the most relevant NADPH oxidase (NOX) isoforms, NOX2 and NOX4, in the mechanism of action. Main methods 60-min partial liver ischemia was induced in Sprague-Dawley rats in the presence or absence of remote IPC (2 × 10-min limb IR), and hepatic microcirculatory variables were determined through intravital video microscopy and lightguide spectrophotometry during reperfusion. Inflammatory enzyme activities (myeloperoxidase (MPO) and xanthine oxidoreductase (XOR)), cytokine production (TNF-α and HMGB-1), liver necroenzyme levels (AST, ALT and LDH) and NOX2 and NOX4 protein expression changes (Western blot analysis) were assayed biochemically. Key findings In this setting, remote IPC significantly decreased the IR-induced hepatic NOX2 expression, but the NOX4 expression remained unchanged. The remote IPC provided significant, but incomplete protection against the leukocyte-endothelial cell interactions and flow deterioration. Hepatocellular damage (AST, ALT and LDH release), cytokine levels, and XOR and MPO activities also diminished. Significance Remote IPC limited the IR-induced microcirculatory dysfunction, but the protective effect did not affect all NOX homologs (at least not NOX4). The residual damage and inflammatory activation could well be linked to the unchanging NOX4 activity.

Original languageEnglish
Pages (from-to)14-21
Number of pages8
JournalLife Sciences
Volume105
Issue number1-2
DOIs
Publication statusPublished - Jun 6 2014

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Xanthine Dehydrogenase
Ischemic Preconditioning
NADPH Oxidase
Liver
Peroxidase
Reperfusion
Protein Isoforms
HMGB Proteins
Ischemia
Cytokines
Endothelial cells
Spectrophotometry
Enzyme activity
Superoxides
Deterioration
Rats
Microscopic examination
Chemical activation
Enzymes
Video Microscopy

Keywords

  • Inflammation
  • Intravital video microscopy
  • Microcirculation
  • Modified spectrophotometry
  • NOX2
  • NOX4
  • Polymorphonuclear leukocytes

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Remote ischemic preconditioning differentially affects NADPH oxidase isoforms during hepatic ischemia-reperfusion. / Garab, Dénes; Fet, Ngwi; Szabó, Andrea; Tolba, René H.; Borós, M.; Hartmann, Petra.

In: Life Sciences, Vol. 105, No. 1-2, 06.06.2014, p. 14-21.

Research output: Contribution to journalArticle

Garab, Dénes ; Fet, Ngwi ; Szabó, Andrea ; Tolba, René H. ; Borós, M. ; Hartmann, Petra. / Remote ischemic preconditioning differentially affects NADPH oxidase isoforms during hepatic ischemia-reperfusion. In: Life Sciences. 2014 ; Vol. 105, No. 1-2. pp. 14-21.
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