Skip to main content

Advertisement

Log in

Poly(ADP-ribose) Polymerase inhibition improves wound healing in the colonic anastomoses of rats

  • Original Article
  • Published:
European Surgery Aims and scope Submit manuscript

Summary

Aims

Colonic anastomosis is a widely used surgical procedure and leads to morbidity and mortality with anastomotic leaks. It has been shown that PARP inhibition has beneficial effects against various pathological conditions. In this study, we aimed to evaluate the possible effects of 3-aminobenzamide (3-AB), a PARP-1 inhibitor, on experimental wound healing and tensile strength in the colonic anastomosis of rats.

Methods

A total of 14 Sprague-Dawley rats were divided into two random groups of equal number: Control and 3-AB groups. Control group was given standard left colon resection and end-to-end anastomosis; 3-AB group was given colonic resection + anastomosis + received 3-AB. 3-AB group received 20 mg/kg/day 3-AB intraperitoneally following surgical procedure and continued once a day for consecutive 4 days. A relaparatomy was given on the 5th day to evaluate malondialdehyde (MDA), myeloperoxidase (MPO), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), interleukin (IL)-10, IL-6, tumor necrosis factor-alpha (TNF-α), hydroxy (OH)-proline levels and anastomotic burst pressure.

Results

The burst pressure values and the tissue OH-proline levels increased in the treatment group significantly compared with controls. Additionally, when compared the control group, tissue MDA, MPO, TNF-α and IL-10 levels were markedly decreased while tissue SOD and GSH-Px activities were statistically increased in the treatment group (p < 0.05).

Conclusion

Our data showed that 3-AB medication after colonic surgery increased the mechanical tissue strength of anastomotic line in rats. Consequently, these findings suggest that it would be possible to improve the anastomotic wound healing by using PARP inhibitors, and decrease the anastomotic complication rates.

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
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Buchs NC, Gervaz P, Secic M, Bucher P, Mugnier-Konrad B, Morel P. Incidence, consequences, and risk factors for anastomotic dehiscence after colorectal surgery: a prospective monocentric study. Int J Colorectal Dis. 2008;23(3):265–70.

    Article  PubMed  Google Scholar 

  2. Vilz TO, Sommer N, Kahl P, Pantelis D, Kalff JC, Wehner S. Oral CPSI-2364 treatment prevents postoperative ileus in swine without impairment of anastomotic healing. Cell Physiol Biochem. 2013;32(5):1362–73.

    Article  CAS  PubMed  Google Scholar 

  3. Kabali B, Girgin S, Gedik E, Ozturk H, Kale E, Buyukbayram H N-acetylcysteine prevents deleterious effects of ischemia/reperfusion injury on healing of colonic anastomosis in rats. Eur Surg Res. 2009;43(1):8–12.

    Article  CAS  PubMed  Google Scholar 

  4. Thompson SK, Chang EY, Jobe BA. Clinical review: healing in gastrointestinal anastomoses, part I. Microsurgery. 2006;26(3):131–6.

    Article  PubMed  Google Scholar 

  5. Robson MC, Steed DL, Franz MG. Wound healing: biologic features and approaches to maximize healing trajectories. Curr Probl Surg. 2001;38(2):72–140.

    Article  CAS  PubMed  Google Scholar 

  6. Dubay DA, Franz MG. Acute wound healing: the biology of acute wound failure. Surg Clin North Am. 2003;83(3):463–81.

    Article  PubMed  Google Scholar 

  7. Witte MB, Barbul A General principles of wound healing. Surg Clin North Am. 1997;77(3):509–28.

    Article  CAS  PubMed  Google Scholar 

  8. Rijcken E, Sachs L, Fuchs T, Spiegel HU, Neumann PA. Growth factors and gastrointestinal anastomotic healing. J Surg Res. 2014;187(1):202–10.

    Article  CAS  PubMed  Google Scholar 

  9. Huls M, Russel FG, Masereeuw R. The role of ATP binding cassette transporters in tissue defense and organ regeneration. J Pharmacol Exp Ther. 2009;328(1):3–9.

    Article  CAS  PubMed  Google Scholar 

  10. Howard JD, Sarojini H, Wan R, Chien S. Rapid granulation tissue regeneration by intracellular ATP delivery–a comparison with Regranex. PLoS One. 2014;9(3):e91787.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Efron DT, Most D, Shi HP, Tantry US, Barbul A. Modulation of growth factor and cytokine expression by nitric oxide during rat colon anastomotic healing. J Gastrointest Surg. 2003;7(3):393–9.

    Article  PubMed  Google Scholar 

  12. Garcia JG, Criado FJ, Persona MA, Alonso AG. Healing of colonic ischemic anastomoses in the rat: role of superoxide radicals. Dis Colon Rectum. 1998;41(7):892–5.

    Article  CAS  PubMed  Google Scholar 

  13. Virag L, Szabo E, Bakondi E, Bai P, Gergely P, Hunyadi J, et al. Nitric oxide-peroxynitrite-poly(ADP-ribose) polymerase pathway in the skin. Exp Dermatol. 2002;11(3):189–202.

    Article  CAS  PubMed  Google Scholar 

  14. Lindahl T, Satoh MS, Poirier GG, Klungland A. Post-translational modification of poly(ADP-ribose) polymerase induced by DNA strand breaks. Trends Biochem Sci. 1995;20(10):405–11.

    Article  CAS  PubMed  Google Scholar 

  15. Szabo C, Zingarelli B, O’Connor M, Salzman AL. 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. 1996;93(5):1753–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Naziroglu M. New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res. 2007;32(11):1990–2001.

    Article  CAS  PubMed  Google Scholar 

  17. El-Hamoly T, El-Denshary ES, Saad SM, El-Ghazaly MA. 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model. Wound Repair Regen. 2015;23:672–84.

    Article  PubMed  Google Scholar 

  18. El-Hamoly T, Hegedus C, Lakatos P, Kovacs K, Bai P, El-Ghazaly MA, et al. Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. Mol Med. 2014;20:363–71.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Byun YS, Kang B, Yoo YS, Joo CK. Poly(ADP-ribose) polymerase inhibition improves corneal epithelial innervation and wound healing in diabetic rats. Invest Ophthalmol Vis Sci. 2015;56(3):1948–55.

    Article  PubMed  Google Scholar 

  20. Guven A, Demirbag S, Uysal B, Topal T, Erdogan E, Korkmaz A, et al. Effect of 3-amino benzamide, a poly(adenosine diphosphate-ribose) polymerase inhibitor, in experimental caustic esophageal burn. J Pediatr Surg. 2008;43(8):1474–9.

    Article  PubMed  Google Scholar 

  21. Sarras MP Jr., Mason S, McAllister G, Intine RV. Inhibition of poly-ADP ribose polymerase enzyme activity prevents hyperglycemia-induced impairment of angiogenesis during wound healing. Wound Repair Regen. 2014;22(5):666–70.

    Article  PubMed  Google Scholar 

  22. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.

    CAS  PubMed  Google Scholar 

  23. Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.

    Article  CAS  PubMed  Google Scholar 

  24. Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497–500.

    CAS  PubMed  Google Scholar 

  25. Schierwagen C, Bylund-Fellenius AC, Lundberg C. Improved method for quantification of tissue PMN accumulation measured by myeloperoxidase activity. J Pharmacol Methods. 1990;23(3):179–86.

    Article  CAS  PubMed  Google Scholar 

  26. Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158–69.

    CAS  PubMed  Google Scholar 

  27. Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29(3):225–9.

    Article  CAS  PubMed  Google Scholar 

  28. Rieder F, Brenmoehl J, Leeb S, Scholmerich J, Rogler G. Wound healing and fibrosis in intestinal disease. Gut. 2007;56(1):130–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Guo S, Dipietro LA. Factors affecting wound healing. J Dent Res. 2010;89(3):219–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Schraufstatter IU, Hinshaw DB, Hyslop PA, Spragg RG, Cochrane CG. Oxidant injury of cells. DNA strand-breaks activate polyadenosine diphosphate-ribose polymerase and lead to depletion of nicotinamide adenine dinucleotide. J Clin Invest. 1986;77(4):1312–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kim JH, Suk MH, Yoon DW, Kim HY, Jung KH, Kang EH, et al. Inflammatory and transcriptional roles of poly (ADP-ribose) polymerase in ventilator-induced lung injury. Crit Care. 2008;12(4):R108.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Szabo C. Poly(ADP-ribose) polymerase activation by reactive nitrogen species—relevance for the pathogenesis of inflammation. Nitric Oxide. 2006;14(2):169–79.

    Article  CAS  PubMed  Google Scholar 

  33. Wang J, Wan R, Mo Y, Li M, Zhang Q, Chien S. Intracellular delivery of adenosine triphosphate enhanced healing process in full-thickness skin wounds in diabetic rabbits. Am J Surg. 2010;199(6):823–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Poyrazoglu Y, Topal T, Yuksel R, Bircan FS, Simsek K, Gocgeldi E, et al. Effects of hyperbaric oxygen and preconditioning on wound healing in colonic anastomoses. J Invest Surg. 2015;28(4):188–95.

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to R. Yuksel.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ersoz, N., Poyrazoglu, Y., Yuksel, R. et al. Poly(ADP-ribose) Polymerase inhibition improves wound healing in the colonic anastomoses of rats. Eur Surg 48, 115–121 (2016). https://doi.org/10.1007/s10353-015-0365-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10353-015-0365-1

Keywords

Navigation