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  • Open Access

Effect of HO-3089 PARP inhibitor on inflammatory response

  • 1,
  • 1,
  • 1,
  • 1,
  • 2 and
  • 1
Critical Care201115 (Suppl 1) :P252

https://doi.org/10.1186/cc9672

  • Published:

Keywords

  • Systemic Inflammation
  • Sham Group
  • Rectal Temperature
  • PARP Inhibition
  • Cecal Ligation

Introduction

The activation of poly-ADP-ribose-polymerase enzyme (PARP) plays an important role in the pathophysiology of sepsis [1]. In previous animal models, lipopolysaccharide-induced systemic inflammatory response was significantly reduced by the inhibition of PARP [2]. The aim of our study was to investigate the effect of PARP inhibition on systemic inflammation in a septic animal model.

Methods

In a prospective, randomized study, anaesthetized CFY rats were divided into four groups (five/group): cecal ligation group (CL), cecal ligation and punction group (CLP), CLP with PARP inhibition (CLP+Pi) group and sham group. PARP inhibition was performed by HO-3089 (a novel PARP inhibitor) given intraperitoneally (10 mg/kg). Heart rate, invasive blood pressure and the rectal temperature were monitored. Data were recorded every 15 minutes. To identify the inflammatory response, IL-6 and TNFα were measured by quantitative sandwich enzyme immunoassay technique. Blood samples were taken before the CLP (t0), 2 hours (t1) and 6 hours (t2) after the CLP.

Results

IL-6 and TNFα were significantly higher in the CLP and CLP+Pi groups at t2 as compared with t0 (CLP: PIL-6 < 0.001, PTNFα < 0.001; CLP+Pi:PIL-6 = 0.002, PTNFα < 0.001), and also as compared with the CL and sham groups at t2 (CL vs. CLP: PIL-6 < 0.001, PTNFα = 0.002; CL vs. CLP+Pi: PIL-6 = 0.008, PTNFα = 0.002; sham vs. CLP: pIL-6 < 0.001, PTNFα = 0.002; sham vs. CLP+Pi: PIL-6 = 0.011, PTNFα = 0.002). Although in the CLP+Pi group theIL-6 level was lower than in the CLP group at t2, but the difference was not significant (P = 0.074). There was no significant difference in TNFα between the CLP and CLP+Pi groups either.

Conclusions

The initial results of this study could not show a significant effect of the HO-3089 PARP inhibitor in CLP caused systemic inflammatory response. However, the tendency of lower IL-6 in the treated group warrants the completion of the experiment.

Authors’ Affiliations

(1)
University of Pecs, Hungary
(2)
University of Szeged, Hungary

References

  1. Lobo SM, et al.: J Surg Res. 2005, 129: 292-297. 10.1016/j.jss.2005.05.018View ArticlePubMedGoogle Scholar
  2. Veres B, et al.: Biochem Pharmacol. 2003, 65: 1373-1382. 10.1016/S0006-2952(03)00077-7View ArticlePubMedGoogle Scholar

Copyright

© Nemeth et al. 2011

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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