Effect of PJ-34 PARP-Inhibitor on Rat Liver Microcirculation and Antioxidant Status

Attila Szijártó, Enkhjargal Batmunkh, Oszkár Hahn, Zoltán Mihály, Adám Kreiss, András Kiss, Gábor Lotz, Zsuzsa Schaff, László Váli, Anna Blázovics, Domokos Geró, Csaba Szabó, Péter Kupcsulik

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    10 Scopus citations

    Abstract

    Background: Ischemia-reperfusion (I-R) injury during liver resection leads to the production of toxic free radicals and oxidants that influence the microcirculation. DNA single-strand breaks can be induced by these reactive species. In response to excessive DNA damage, PARP [poly(ADP-ribose) polymerase] becomes overactivated, which can lead to cellular ATP depletion and cell death. The aim of our study was to evaluate whether PARP is expressed in post-ischemic liver, and to examine the effect of the administration of PJ-34 PARP inhibitor on liver function, histopathology, terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) reaction, and the oxidative state of the liver after injury. Methods: Male Wistar rats (weighing 250 g) underwent 60 min of normothermic, segmental liver ischemia followed by 30 min of reperfusion. The animals (n = 45) were divided into three groups: sham operated; I-R (control) treated with saline; and PJ-34 pre-treated (10 mg/kg i.v.). Hepatic microcirculation was monitored by a laser Doppler flowmeter. The reperfusion was characterized as the integral of the reperfusion area (RA) and the maximal plateau (PM). Histological alterations, TUNEL-reaction, serum, and liver tissue antioxidant levels, as well as serum ALT and AST levels were measured. Results: Upon reperfusion, the PJ-34 group had significantly (P < 0.05) higher flow rates than control groups (PMPJ-34: 58%, PMcontrol: 37%; RAPJ-34.: 48%, RAcontrol: 25%). At the end of the 30 min reperfusion, PJ-34 resulted in significantly (P < 0.05) lower serum ALT and AST levels and chemiluminescent intensity (free radicals) of the liver. The liver's free SH-group concentration and H-donor ability of the plasma was elevated in the PARP-inhibitor treated group. Positive staining for TUNEL, after PJ-34 pre-treatment was significantly increased (P < 0.05); in contrast, the control tissues were less positively stained for TUNEL but necrotic tissue was abundant. Conclusion: PARP plays a pathogenetic role in the deterioration of the hepatic microcirculation and promotes hepatocellular necrosis in liver reperfusion injury.

    Original languageEnglish (US)
    Pages (from-to)72-80
    Number of pages9
    JournalJournal of Surgical Research
    Volume142
    Issue number1
    DOIs
    StatePublished - Sep 1 2007

    Keywords

    • PARP
    • PJ-34
    • apoptosis
    • ischemia
    • laser Doppler flowmeter
    • liver
    • reperfusion

    ASJC Scopus subject areas

    • Surgery

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  • Cite this

    Szijártó, A., Batmunkh, E., Hahn, O., Mihály, Z., Kreiss, A., Kiss, A., Lotz, G., Schaff, Z., Váli, L., Blázovics, A., Geró, D., Szabó, C., & Kupcsulik, P. (2007). Effect of PJ-34 PARP-Inhibitor on Rat Liver Microcirculation and Antioxidant Status. Journal of Surgical Research, 142(1), 72-80. https://doi.org/10.1016/j.jss.2006.08.003