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Erschienen in: European Surgery 2/2016

01.04.2016 | Original Article

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

verfasst von: N. Ersoz, Y. Poyrazoglu, Dr. R. Yuksel, B. Uysal, T. Topal, S. K. Tuncer, E. Gocgeldi, A. Korkmaz

Erschienen in: European Surgery | Ausgabe 2/2016

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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.
Literatur
1.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
2.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
3.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
4.
Zurück zum Zitat Thompson SK, Chang EY, Jobe BA. Clinical review: healing in gastrointestinal anastomoses, part I. Microsurgery. 2006;26(3):131–6.CrossRefPubMed Thompson SK, Chang EY, Jobe BA. Clinical review: healing in gastrointestinal anastomoses, part I. Microsurgery. 2006;26(3):131–6.CrossRefPubMed
5.
Zurück zum Zitat Robson MC, Steed DL, Franz MG. Wound healing: biologic features and approaches to maximize healing trajectories. Curr Probl Surg. 2001;38(2):72–140.CrossRefPubMed Robson MC, Steed DL, Franz MG. Wound healing: biologic features and approaches to maximize healing trajectories. Curr Probl Surg. 2001;38(2):72–140.CrossRefPubMed
6.
Zurück zum Zitat Dubay DA, Franz MG. Acute wound healing: the biology of acute wound failure. Surg Clin North Am. 2003;83(3):463–81.CrossRefPubMed Dubay DA, Franz MG. Acute wound healing: the biology of acute wound failure. Surg Clin North Am. 2003;83(3):463–81.CrossRefPubMed
7.
Zurück zum Zitat Witte MB, Barbul A General principles of wound healing. Surg Clin North Am. 1997;77(3):509–28.CrossRefPubMed Witte MB, Barbul A General principles of wound healing. Surg Clin North Am. 1997;77(3):509–28.CrossRefPubMed
8.
Zurück zum Zitat Rijcken E, Sachs L, Fuchs T, Spiegel HU, Neumann PA. Growth factors and gastrointestinal anastomotic healing. J Surg Res. 2014;187(1):202–10.CrossRefPubMed Rijcken E, Sachs L, Fuchs T, Spiegel HU, Neumann PA. Growth factors and gastrointestinal anastomotic healing. J Surg Res. 2014;187(1):202–10.CrossRefPubMed
9.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
10.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
11.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
12.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
13.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
14.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
15.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Naziroglu M. New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res. 2007;32(11):1990–2001.CrossRefPubMed Naziroglu M. New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res. 2007;32(11):1990–2001.CrossRefPubMed
17.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
18.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
19.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
20.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
21.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
22.
Zurück zum Zitat Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.PubMed Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951;193(1):265–75.PubMed
23.
Zurück zum Zitat Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.CrossRefPubMed Ohkawa H, Ohishi N, Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem. 1979;95(2):351–8.CrossRefPubMed
24.
Zurück zum Zitat Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497–500.PubMed Sun Y, Oberley LW, Li Y. A simple method for clinical assay of superoxide dismutase. Clin Chem. 1988;34(3):497–500.PubMed
25.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
26.
Zurück zum Zitat Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158–69.PubMed Paglia DE, Valentine WN. Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med. 1967;70(1):158–69.PubMed
27.
Zurück zum Zitat Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29(3):225–9.CrossRefPubMed Reddy GK, Enwemeka CS. A simplified method for the analysis of hydroxyproline in biological tissues. Clin Biochem. 1996;29(3):225–9.CrossRefPubMed
30.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
31.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
32.
Zurück zum Zitat Szabo C. Poly(ADP-ribose) polymerase activation by reactive nitrogen species—relevance for the pathogenesis of inflammation. Nitric Oxide. 2006;14(2):169–79.CrossRefPubMed Szabo C. Poly(ADP-ribose) polymerase activation by reactive nitrogen species—relevance for the pathogenesis of inflammation. Nitric Oxide. 2006;14(2):169–79.CrossRefPubMed
33.
Zurück zum Zitat 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.CrossRefPubMedPubMedCentral 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.CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat 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.CrossRefPubMed 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.CrossRefPubMed
Metadaten
Titel
Poly(ADP-ribose) Polymerase inhibition improves wound healing in the colonic anastomoses of rats
verfasst von
N. Ersoz
Y. Poyrazoglu
Dr. R. Yuksel
B. Uysal
T. Topal
S. K. Tuncer
E. Gocgeldi
A. Korkmaz
Publikationsdatum
01.04.2016
Verlag
Springer Vienna
Erschienen in
European Surgery / Ausgabe 2/2016
Print ISSN: 1682-8631
Elektronische ISSN: 1682-4016
DOI
https://doi.org/10.1007/s10353-015-0365-1

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