RESEARCH PAPER
Year : 2015  |  Volume : 6  |  Issue : 1  |  Page : 13-23

Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression


1 Department of Anaesthesia and Critical Care, University Hospital Würzburg, Germany
2 Department of Pathology, Klinikum Nürnberg, Nürnberg, Germany
3 Department of Anaesthesia and Critical Care, University Hospital Würzburg, Germany; Department of Medicinal Chemistry, University of Vienna, Vienna, Austria
4 Department of Anaesthesia and Critical Care, University Hospital Würzburg; Department of Anesthesiology and Critical Care Medicine, University Medical Center, Freiburg, Germany
5 Department of General, Visceral, Vascular, and Paediatric Surgery (Department of Surgery I), University of Würzburg, Würzburg, Germany

Correspondence Address:
Martin A Schick
Department of Anaesthesia and Critical Care, University Hospital Würzburg
Germany
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0976-500X.149138

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Objective: To investigate the impact of the phophodiesterase-4 inhibition (PD-4-I) with rolipram on hepatic integrity in lipopolysaccharide (LPS) induced hyperinflammation. Materials and Methods: Liver microcirculation in rats was obtained using intravital microscopy. Macrohemodynamic parameters, blood assays, and organs were harvested to determine organ function and injury. Hyperinflammation was induced by LPS and PD-4-I rolipram was administered intravenously one hour after LPS application. Cell viability of HepG2 cells was measured by EZ4U-kit based on the dye XTT. Experiments were carried out assessing the influence of different concentrations of tumor necrosis factor alpha (TNF-α) and LPS with or without PD-4-I. Results: Untreated LPS-induced rats showed significantly decreased liver microcirculation and increased hepatic cell death, whereas LPS + PD-4-I treatment could improve hepatic volumetric flow and cell death to control level whithout influencing the inflammatory impact. In HepG2 cells TNF-α and LPS significantly reduced cell viability. Coincubation with PD-4-I increased HepG2 viability to control levels. The heme oxygenase 1 (HO-1) pathway did not induce the protective effect of PD-4-I. Conclusion: Intravenous PD-4-I treatment was effective in improving hepatic microcirculation and hepatic integrity, while it had a direct protective effect on HepG2 viability during inflammation.


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