Effect of 3-aminobenzamide, an inhibitor of poly (ADP-ribose) synthetase, on the expression of P-selecitn and intercellular adhesion molecule-1 in myocardialischemia-reperfusion

Basilia Zingarelli, Salvatore Cuzzocrea, Andrew L. Salzman, Csabe Szabó

    Research output: Contribution to journalArticlepeer-review


    Introduction: In vitro studies have demonstrated dm the oxidative injury in various cell types is, in part, related to DNA single strand breakage, and consequent activation of the nuclear enzyme poly (ADP-nbose) syntheuse (PARS). Recent data also demonstrate that pharmacological inhibition of PARS activity reduces inrarct size and prevents neutrophil accumulation into the reperrused myocanSal tissue. Here we evaluated the effect of the PARS inhibitor 3-aminobenzamide on P-selectin and ICAM-1 expression in a rat model of myocardial injury. Methods: Myocardial ischemia and reperfusion was induced in male anaesthertized Wistar rats. Myocardial ischemia and reperfusion was pel fumed by opening die chest and occluding the left main coronary artery by a 4.0 silk ligature. The occlusion was released after 1 h, and the ischemic period was followed by 1 h reperfusion. Hearts were removed for immuno-histochemical analysis. One group of animals received 3-anunobenzamide as a intravenous bolus 10 minutes before reperfnsion (10 mg/kg) followed by infusion of 10 mg/kg/h during reperfusion. P-selectin and ICAM-1 localization was evaluated in myocardial sections by immimohistochemistry. Five μm thick frozen sections were fixed in paraformaldehyde and incubated in 2% normal horse or goat serum for 1 h in order to minimise non specific adsorption. Sections were dien incubated overnight at 4° C with monoclonal antibodies directed at ICAM-1 (CDS4) or polyclonal antibodies directed at P-selectin. Antibodies binding sites were visualized using an avidin-biotin peroxidase complex immunoperoxidase technique. Results: Reperfused myocardial tissue sections showed positive staining for Pselectin, which was mainly localized in die vascular endothelial cells. Little specific staining was observed in sham-controls. Staining of myocardial tissue sections obtained from sham operated rats with anti-ICAM-1 antibody showed a weak but diffuse staining demonstrating that ICAM-1 is constitutively expressed in endothelial cells. However, after myocardial ischemia and reperfusion, die staining intensity imitated substantially in the area of early necrosis. Immunohistocbemical staining was mainly lorahml in endothelial vascular wall, but a weak staining was also localized in myocytes within die necrotic lesion. The intensity and degree of P-selectin and ICAM-1 were markedly reduced in tissue sections obtained from rats treated with 3-aminobenzamide prior to reperfusion. Conclusions: Based on the data presented here, we propose that die protective effects of 3-aminobenzamide in inflammation, shock and ischentia-repertusion injury may be, in part, due to inhibition of the expression of adhesion molecules, and subsequent reduction of neutrophil-mediated cellular injury.

    Original languageEnglish (US)
    Pages (from-to)A35
    JournalCritical care medicine
    Issue number1 SUPPL.
    StatePublished - Dec 1 1998

    ASJC Scopus subject areas

    • Critical Care and Intensive Care Medicine


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