Journal of Pharmacology and Pharmacotherapeutics

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


Jakob Wollborn1, Christian Wunder1, Jana Stix2, Winfried Neuhaus3, Rapahel R Bruno1, Wolfgang Baar4, Sven Flemming5, Norbert Roewer1, Nicolas Schlegel5, Martin A Schick1 
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

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.


How to cite this article:
Wollborn J, Wunder C, Stix J, Neuhaus W, Bruno RR, Baar W, Flemming S, Roewer N, Schlegel N, Schick MA. Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression.J Pharmacol Pharmacother 2015;6:13-23


How to cite this URL:
Wollborn J, Wunder C, Stix J, Neuhaus W, Bruno RR, Baar W, Flemming S, Roewer N, Schlegel N, Schick MA. Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression. J Pharmacol Pharmacother [serial online] 2015 [cited 2021 Jan 17 ];6:13-23
Available from: http://www.jpharmacol.com/article.asp?issn=0976-500X;year=2015;volume=6;issue=1;spage=13;epage=23;aulast=Wollborn;type=0