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    Journal of Pharmacology and PharmacotherapeuticsNOW IN
    Article

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

    Jakob Wollborn2★, Christian Wunder2, Jana Stix4, Winfried Neuhaus2,5, Rapahel R. Bruno2, Wolfgang Baar2,6, Sven Flemming3, Norbert Roewer2, Nicolas Schlegel3, Martin A.Schick2★ Corresponding author

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

    CORRESPONDENCE

    Jakob Wollborn

    Department of General, Visceral, Vascular, and Paediatric Surgery (Department of Surgery I), University of Würzburg, Würzburg.

    schick_m@ukw.de

    Received: 03-03-2014; Revised: 09-07-2014; Accepted: 17-11-2014.

    Volume 6, Issue 1 · pp. · PUBLISHED 2015 · DOI: 10.4103/0976-500X.149138

    View on J Pharmacol. Pharmacother. original site ↗

    ABSTRACT

    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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      Wollborn, J., Wunder, C., Stix, J., Neuhaus, W., Bruno, R. R., Baar, W., Flemming, S., Roewer, N., Schlegel, N., & A.Schick, M. (2015). Phosphodiesterase-4 inhibition with rolipram attenuates hepatocellular injury in hyperinflammation in vivo and in vitro without influencing inflammation and HO-1 expression. Journal of Pharmacology and Pharmacotherapeutics, 6(1). https://doi.org/10.4103/0976-500X.149138