Skip to main content
Log in

Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model

  • Original Article
  • Published:
Inflammopharmacology Aims and scope Submit manuscript

Abstract

Objectives

Paraquat (PQ) is a widely used herbicide. Exposure to PQ at toxic doses can result in fatal acute lung injury. Inhibition of the poly-(ADP-ribose) polymerase (PARP) enzyme alleviates inflammation and necrosis in various pathologies. Here we aimed to evaluate the effects of PARP inhibition on PQ-induced lung damage in a rat experimental model.

Methods

Female Sprague-Dawley rats (n = 24) were allocated into three groups: sham, PQ and PQ + 3-aminobenzamide (3-AB) that is a PARP inhibitor, groups. Experimental lung injury was induced by administration of 15 mg/kg PQ intraperitoneally in PQ and PQ + 3-AB groups. 3-AB (10 mg/kg twice per day) was administered to the PQ + 3-AB group for four consecutive days. The animals were killed on the fifth day following PQ administration. Lung tissue and blood samples were collected and stored until analysis.

Results

Serum lactate dehydrogenase (LDH) and neopterin levels, tissue oxidative stress parameters, transforming growth factor-beta1 (TGF-β) levels and histological injury scores in the PQ + 3-AB group were significantly lower than in the PQ group (P < 0.05, PQ vs. PQ + 3-AB). Total antioxidant capacity in the PQ + 3-AB group was significantly higher than in the PQ group (P < 0.05, PQ + 3-AB vs. PQ).

Conclusion

Our results suggested that the use of PARP inhibitors following PQ toxicity might be useful for minimizing lung injury due to paraquat toxicity.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  • Alrashed M, Abougoush M, Akgul EO et al (2002) Detection method of serum and urine neopterin levels by high performance liquid chromatography and clinical applications. Gulhane MJ 44:273–277

    Google Scholar 

  • Bühling F, Thölert G, Kaiser D et al (1999) Increased release of transforming growth factor (TGF)-beta1, TGF-beta2, and chemoattractant mediators in pneumonia. J Interferon Cytokine Res 19(3):271–278

    Article  PubMed  Google Scholar 

  • Cuzzocrea S, McDonald MC, Mazzon E et al (2002) Effects of 5-aminoisoquinolinone, a water-soluble, potent inhibitor of the activity of poly(ADP-ribose) polymerase, in a rodent model of lung injury. Biochem Pharmacol 63:293–304

    Article  CAS  PubMed  Google Scholar 

  • Cuzzocrea S (2005) Shock, inflammation and PARP. Pharmacol Res 52(1):72–82

    Article  CAS  PubMed  Google Scholar 

  • Celik SE, Ozyurek M, Guclu K et al (2012) Differences in responsivity of original cupric reducing antioxidant capacity and cupric-bathocuproine sulfonate assays to antioxidant compounds. Anal Biochem 423(1):36–38

    Article  PubMed  Google Scholar 

  • Drent M, Cobben NA, Henderson RF et al (1996) Usefulness of lactate dehydrogenase and its isoenzymes as indicators of lung damage or inflammation. Eur Respir J 9(8):1736–1742

    Article  CAS  PubMed  Google Scholar 

  • Durak I, Yurtarslanl Z, Canbolat O et al (1993) A methodological approach to superoxide dismutase (SOD) activity assay based on inhibition of nitroblue tetrazolium (NBT) reduction. Clin Chim Acta 214(1):103–104

    Article  CAS  PubMed  Google Scholar 

  • Gebhard C, Stähli BE, Shi Y et al (2011) Poly(ADP-ribose) polymerase-1 protects from oxidative stress induced endothelial dysfunction. Biochem Biophys Res Commun 414(4):641–646

    Article  CAS  PubMed  Google Scholar 

  • Gocgeldi E, Uysal B, Korkmaz A et al (2008) Establishing the use of melatonin as an adjuvant therapeutic against paraquat-induced lung toxicity in rats. Exp Biol Med (Maywood) 233(9):1133–1141

    Article  CAS  Google Scholar 

  • Kao SJ, Liu DD, Su CF et al (2007) Niacinamide abrogates the organ dysfunction and acute lung injury caused by endotoxin. J Cardiovasc Pharmacol 50(3):333–342

    Article  CAS  PubMed  Google Scholar 

  • Kaufmann P, Tilz GP, Demel U et al (1998) Neopterin plasma concentrations predict the course of severe acute pancreatitis. Clin Chem Lab Med 36:29–34

    Article  CAS  PubMed  Google Scholar 

  • Kiefmann R, Heckel K, Doerger M et al (2004) Role of PARP on iNOS pathway during endotoxin-induced acute lung injury. Intensive Care Med 30(7):1421–1431

    Article  PubMed  Google Scholar 

  • Koksel O, Yildirim C, Cinel L et al (2005) Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats. Pharmacol Res 51(5):453–462

    Article  CAS  PubMed  Google Scholar 

  • Liaudet L, Pacher P, Mabley JG et al (2002) Activation of poly(ADP-Ribose) polymerase-1 is a central mechanism of lipopolysaccharide-induced acute lung inflammation. Am J Respir Crit Care Med 165(3):372–377

    Article  PubMed  Google Scholar 

  • Lindahl T, Satoh MS, Poirier GG, Klungland (1995) Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem Sci 20(10):405–411

    Article  CAS  PubMed  Google Scholar 

  • Lowry OH, Rosebrough NJ, Farr AL et al (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275

    CAS  PubMed  Google Scholar 

  • Morán JM, Ortiz-Ortiz MA, Ruiz-Mesa LM et al (2010) Nitric oxide in paraquat mediated toxicity: a review. J Biochem Mol Toxicol 24(6):402–409

    Article  PubMed  Google Scholar 

  • Murakami K, Enkhbaatar P, Shimoda K et al (2004) Inhibition of poly(ADP-ribose) polymerase attenuates acute lung injury in an ovine model of sepsis. Shock 21:126–133

    Article  CAS  PubMed  Google Scholar 

  • Naziroglu M (2007) New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res 32:1990–2001

    Article  CAS  PubMed  Google Scholar 

  • Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358

    Article  CAS  PubMed  Google Scholar 

  • Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70:158–169

    CAS  PubMed  Google Scholar 

  • Suntres ZA (2000) Role of antioxidants in paraquat toxicity. Toxicology 180:65–77

    Article  Google Scholar 

  • Szabo C, Zingarelli B, O’Connor M et al (1996) DNA strand breakage, activation of poly (ADP-ribose) synthetase, and cellular energy depletion are involved in the cytotoxicity of macrophages and smooth muscle cells exposed to peroxynitrite. Proc Natl Acad Sci USA 93:1753–1758

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tylman M, Bengtson JP, Hyllner M et al (2006) Release of PMN elastase, TGF-beta1 and neopterin during blood storage; unfiltered versus filtered blood. Transfus Apher Sci 35(2):97–102

    Article  PubMed  Google Scholar 

  • Virag L, Szabo E, Bakondi E et al (2002) Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. Exp Dermatol 11:189–202

    Article  CAS  PubMed  Google Scholar 

  • Yamanel L, Kaldirim U, Oztas Y et al (2011) Ozone therapy and hyperbaric oxygen treatment in lung injury in septic rats. Int J Med Sci. 3 8(1):48–55

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bulent Uysal.

Ethics declarations

Conflict of interest

The authors report no declarations of interest. We have not been funded by any individual or organization.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Tuncer, S.K., Altinel, S., Toygar, M. et al. Poly-ADP-ribose polymerase inhibition provides protection against lung injury in a rat paraquat toxicity model. Inflammopharmacol 24, 155–161 (2016). https://doi.org/10.1007/s10787-016-0268-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10787-016-0268-1

Keywords

Navigation