The clinically used PARP inhibitor olaparib improves organ function, suppresses inflammatory responses and accelerates wound healing in a murine model of third-degree burn injury

British Journal of Pharmacology

Volumn 175, Issue 2, 2018, Pages 232-245

  Ahmad, Akbar ^a   Olah, Gabor ^a   Herndon, David N ^a,b   Szabo, Csaba ^a,b  

^a University of Texas Medical Branch School of Medicine   (United States)

^b SHRINERS HOSPITALS FOR CHILDREN   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALANINE AMINOTRANSFERASE; AMYLASE; CREATININE; CXCL1 CHEMOKINE; EOTAXIN; GAMMA INTERFERON; GRANULOCYTE COLONY STIMULATING FACTOR; GRANULOCYTE MACROPHAGE COLONY STIMULATING FACTOR; INTERLEUKIN 10; INTERLEUKIN 12; INTERLEUKIN 13; INTERLEUKIN 1BETA; INTERLEUKIN 3; INTERLEUKIN 4; INTERLEUKIN 6; MACROPHAGE INFLAMMATORY PROTEIN 1ALPHA; MALONALDEHYDE; MYELOPEROXIDASE; NITROGEN; OLAPARIB; TUMOR NECROSIS FACTOR; UREA; AUTACOID; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE INHIBITOR; PEROXIDASE; PHTHALAZINE DERIVATIVE; PIPERAZINE DERIVATIVE; TROPONIN T;

ALANINE AMINOTRANSFERASE BLOOD LEVEL; AMYLASE BLOOD LEVEL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; BURN; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DRUG REPOSITIONING; FEASIBILITY STUDY; INFLAMMATION; KIDNEY DYSFUNCTION; LIVER DYSFUNCTION; LIVER PROTECTION; MALE; MOUSE; MURINE MODEL; MUSCLE INJURY; NONHUMAN; ORGAN INJURY; PANCREATIC INSUFFICIENCY; PRIORITY JOURNAL; PROTEIN BLOOD LEVEL; RENAL PROTECTION; TISSUE LEVEL; UREA NITROGEN BLOOD LEVEL; WOUND HEALING; ANIMAL; BLOOD; CARDIAC MUSCLE; DISEASE MODEL; DRUG EFFECT; LUNG; METABOLISM;

ANIMALS; BURNS; DISEASE MODELS, ANIMAL; INFLAMMATION; INFLAMMATION MEDIATORS; LUNG; MALE; MALONDIALDEHYDE; MICE; MYOCARDIUM; PEROXIDASE; PHTHALAZINES; PIPERAZINES; POLY(ADP-RIBOSE) POLYMERASE INHIBITORS; TROPONIN T; WOUND HEALING;

EID: 85014535974     PISSN: 00071188     EISSN: 14765381     Source Type: Journal    
DOI: 10.1111/bph.13735     Document Type: Article

References (107)

1. Ahmad A, Druzhyna N, Szabo C (2016). Delayed treatment with sodium hydrosulfide improves regional blood flow and alleviates cecal ligation and puncture (CLP)-induced septic shock. Shock 46: 183–193.
2. Ahmad SF, Zoheir KM, Ansari MA, Korashy HM, Bakheet SA, Ashour AE (2015). The role of poly(ADP-ribose) polymerase-1 inhibitor in carrageenan-induced lung inflammation in mice. Mol Immunol 63: 394–405.
3. 2S donor AP39 exert protective effects in a mouse model of burn injury. Pharmacol Res 113: 348–355.
4. Alano CC, Garnier P, Ying W, Higashi Y, Kauppinen TM, Swanson RA (2010). NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J Neurosci 30: 2967–2978.
5. Alexander SPH, Benson HE, Faccenda E, Pawson AJ, Sharman JL, McGrath JC et al. (2015). The Concise Guide to PHARMACOLOGY 2015/16: Overview. Brit J Pharmacol 172: 5729–5743.
6. Alloju SM, Herndon DN, McEntire SJ, Suman OE (2008). Assessment of muscle function in severely burned children. Burns 34: 452–459.
7. Andrabi SA, Kim NS, Yu SW, Wang H, Koh DW, Sasaki M et al. (2006). Poly(ADP-ribose) (PAR) polymer is a death signal. Proc Natl Acad Sci U S A 103: 18308–18313.
8. Asmussen S, Bartha E, Olah G, Sbrana E, Rehberg SW, Yamamoto Y et al. (2011). The angiotensin-converting enzyme inhibitor captopril inhibits poly(adp-ribose) polymerase activation and exerts beneficial effects in an ovine model of burn and smoke injury. Shock 36: 402–409.
9. Avlan D, Taşkinlar H, Unlü A, Oztürk C, Cinel L, Nayci A et al. (2004). The role of poly(ADP-ribose) synthetase inhibition on the intestinal mucosal barrier after thermal injury. Burns 30: 785–792.
10. Avlan D, Unlü A, Ayaz L, Camdeviren H, Nayci A, Aksöyek S (2005). Poly (adp-ribose) synthetase inhibition reduces oxidative and nitrosative organ damage after thermal injury. Pediatr Surg Int 21: 449–455.
11. Ba X, Garg NJ (2011). Signaling mechanism of poly(ADP-ribose) polymerase-1 (PARP-1) in inflammatory diseases. Am J Pathol 178: 946–955.
12. Bai P, Virág L (2012). Role of poly(ADP-ribose) polymerases in the regulation of inflammatory processes. FEBS Lett 586: 3771–3777.
13. Bartha E, Asmussen S, Olah G, Rehberg SW, Yamamoto Y, Traber DL et al. (2011). Burn and smoke injury activates poly(ADP-ribose)polymerase in circulating leukocytes. Shock 36: 144–148.
14. Berger NA, Berger SJ, Gerson SL (1987). DNA repair, ADP-ribosylation and pyridine nucleotide metabolism as targets for cancer chemotherapy. Anticancer Drug Des 2: 203–209.
15. Binu S, Soumya SJ, Kumar VB, Sudhakaran PR (2012). Poly-ADP-ribosylation of vascular endothelial growth factor and its implications on angiogenesis. Adv Exp Med Biol 749: 269–278.
16. Bryant HE, Schultz N, Thomas HD, Parker KM, Flower D, Lopez E et al. (2005). Specific killing of BRCA2-deficient tumours with inhibitors of poly(ADP-ribose) polymerase. Nature 434: 913–917.
17. Burch PM, Greg Hall D, Walker EG, Bracken W, Giovanelli R, Goldstein R et al. (2016). Evaluation of the relative performance of drug-induced skeletal muscle injury biomarkers in rats. Toxicol Sci 150: 247–256.
18. Byun YS, Kang B, Yoo YS, Joo CK (2015). Poly(ADP-ribose) polymerase inhibition improves corneal epithelial innervation and wound healing in diabetic rats. Invest Ophthalmol Vis Sci 56: 1948–1955.
19. Caldini R, Fanti E, Magnelli L, Barletta E, Tanganelli E, Zampieri M et al. (2011). Low doses of 3-aminobenzamide, a poly(ADP-ribose) polymerase inhibitor, stimulate angiogenesis by regulating expression of urokinase type plasminogen activator and matrix metalloprotease 2. Vasc Cell 3: 12.
20. Chambon P, Weill JD, Mandel P (1963). Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. Biochem Biophys Res Commun 11: 39–43.
21. Coletta C, Módis K, Oláh G, Brunyánszki A, Herzig DS, Sherwood ER et al. (2014). Endothelial dysfunction is a potential contributor to multiple organ failure and mortality in aged mice subjected to septic shock: preclinical studies in a murine model of cecal ligation and puncture. Crit Care 18: 511.
22. 2S pathway: functional impairment by hyperglycemia and restoration by DL-α-lipoic acid. Mol Med 21: 1–14.
23. Curtin NJ, Szabo C (2013). Therapeutic applications of PARP inhibitors: anticancer therapy and beyond. Mol Aspects Med 34: 1217–1256.
24. Curtis MJ, Bond RA, Spina D, Ahluwalia A, Alexander SP, Giembycz MA et al. (2015). Experimental design and analysis and their reporting: new guidance for publication in BJP. Br J Pharmacol 172: 3461–3471.
25. Dahiya P (2009). Burns as a model of SIRS. Front Biosci (Landmark Ed) 14: 4962–4967.
26. Deeks ED (2015). Olaparib: first global approval. Drugs 75: 231–240.
27. Drew Y (2015). The development of PARP inhibitors in ovarian cancer: from bench to bedside. Br J Cancer 113: S3–S9.
28. Ebid AA, Omar MT, Abd El Baky AM (2012). Effect of 12-week isokinetic training on muscle strength in adult with healed thermal burn. Burns 38: 61–68.
29. Elenkov IJ (2004). Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 1024: 138–146.
30. El-Hamoly T, El-Denshary ES, Saad SM, El-Ghazaly MA (2015). 3-aminobenzamide, a poly (ADP ribose) polymerase inhibitor, enhances wound healing in whole body gamma irradiated model. Wound Repair Regen 23: 672–684.
31. El-Hamoly T, Hegedűs C, Lakatos P, Kovács K, Bai P, El-Ghazaly MA et al. (2014). Activation of poly(ADP-ribose) polymerase-1 delays wound healing by regulating keratinocyte migration and production of inflammatory mediators. Mol Med 20: 363–371.
32. Farivar AS, Woolley SM, Fraga CH, Thomas R, Salzman AL, Szabo C et al. (2004). Intratracheal poly (ADP) ribose synthetase inhibition ameliorates lung ischemia reperfusion injury. Ann Thorac Surg 77: 1938–1943.
33. Farmer H, McCabe N, Lord CJ, Tutt AN, Johnson DA, Richardson TB et al. (2005). Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy. Nature 434: 917–921.
34. Fatokun AA, Dawson VL, Dawson TM (2014). Parthanatos: mitochondrial-linked mechanisms and therapeutic opportunities. Br J Pharmacol 171: 2000–2016.
35. Finnerty CC, Ali A, McLean J, Benjamin N, Clayton RP, Andersen CR et al. (2014). Impact of stress-induced diabetes on outcomes in severely burned children. J Am Coll Surg 218: 783–795.
36. Finnerty CC, Przkora R, Herndon DN, Jeschke MG (2009). Cytokine expression profile over time in burned mice. Cytokine 45: 20–25.
37. García S, Conde C (2015). The role of poly(ADP-ribose) polymerase-1 in rheumatoid arthritis. Mediators Inflamm 2015: 837250.
38. Gauglitz GG, Herndon DN, Jeschke MG (2008). Insulin resistance postburn: underlying mechanisms and current therapeutic strategies. J Burn Care Res 29: 683–694.
39. Ghonim MA, Pyakurel K, Ibba SV, Wang J, Rodriguez P, Al-Khami AA et al. (2015a). PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice. Clin Sci (Lond) 129: 951–962.
40. Ghonim MA, Pyakurel K, Ibba SV, Wang J, Rodriguez P, Al-Khami AA et al. (2015b). PARP is activated in human asthma and its inhibition by olaparib blocks house dust mite-induced disease in mice. Clin Sci (Lond) 129: 951–962.
41. Gilad E, Zingarelli B, Salzman AL, Szabo C (1997). Protection by inhibition of poly (ADP-ribose) synthetase against oxidant injury in cardiac myoblasts in vitro. J Mol Cell Cardiol 29: 2585–2597.
42. Gonzalez-Rey E, Martínez-Romero R, O'Valle F, Aguilar-Quesada R, Conde C, Delgado M et al. (2007). Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response. PLoS One 2: e1071.
43. Griffin RJ, Curtin NJ, Newell DR, Golding BT, Durkacz BW, Calvert AH (1995). The role of inhibitors of poly(ADP-ribose) polymerase as resistance-modifying agents in cancer therapy. Biochimie 77: 408–422.
44. Guzyk MM, Tykhomyrov AA, Nedzvetsky VS, Prischepa IV, Grinenko TV, Yanitska LV et al. (2016). Poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors reduce reactive gliosis and improve angiostatin levels in retina of diabetic rats. Neurochem Res 41: 2526–2537.
45. Ha HC, Snyder SH (1999). Poly(ADP-ribose) polymerase is a mediator of necrotic cell death by ATP depletion. Proc Natl Acad Sci U S A 96: 13978–13982.
46. Hamahata A, Enkhbaatar P, Lange M, Yamaki T, Sakurai H, Shimoda K et al. (2012). Administration of poly(ADP-ribose) polymerase inhibitor into bronchial artery attenuates pulmonary pathophysiology after smoke inhalation and burn in an ovine model. Burns 38: 1210–1215.
47. Haskó G, Szabo C, Németh ZH, Kvetan V, Pastores SM, Vizi ES (1996). Adenosine receptor agonists differentially regulate IL-10, TNF-alpha, and nitric oxide production in RAW 264.7 macrophages and in endotoxemic mice. J Immunol 157: 4634–4640.
48. Haskó G, Deitch EA, Szabo C, Németh ZH, Vizi ES (2002). Adenosine: a potential mediator of immunosuppression in multiple organ failure. Curr Opin Pharmacol 2: 440–444.
49. Heller B, Bürkle A, Radons J, Fengler E, Jalowy A, Müller M et al. (1994). Analysis of oxygen radical toxicity in pancreatic islets at the single cell level. Biol Chem Hoppe Seyler 375: 597–602.
50. Herndon D (ed) (2012). Total burn care, 4th edn. Elsevier Health Sciences: Amsterdam, The Netherlands.
51. Ito S, Murphy CG, Doubrovina E, Jasin M, Moynahan ME (2016). PARP inhibitors in clinical use induce genomic instability in normal human cells. PLoS One 11: e0159341.
52. Jagtap P, Soriano FG, Virág L, Liaudet L, Mabley J, Szabó E et al. (2002). Novel phenanthridinone inhibitors of poly (adenosine 5'-diphosphate-ribose) synthetase: potent cytoprotective and antishock agents. Crit Care Med 30: 1071–1082.
53. Jagtap P, Szabo C (2005). Poly(ADP-ribose) polymerase and the therapeutic effects of its inhibitors. Nat Rev Drug Discov 4: 421–440.
54. Jeschke MG, Abdullahi A, Burnett M, Rehou S, Stanojcic M (2016). Glucose control in severely burned patients using metformin: an interim safety and efficacy analysis of a phase II randomized controlled trial. Ann Surg 264: 518–527.
55. Kapoor K, Singla E, Sahu B, Naura AS (2015). PARP inhibitor, olaparib ameliorates acute lung and kidney injury upon intratracheal administration of LPS in mice. Mol Cell Biochem 400: 153–162.
56. Kilkenny C, Browne W, Cuthill IC, Emerson M, Altman DG (2010). Animal research: Reporting in vivo experiments: the ARRIVE guidelines. Br J Pharmacol 160: 1577–1579.
57. Lange M, Szabo C, Enkhbaatar P, Connelly R, Horvath E, Hamahata A et al. (2011). Beneficial pulmonary effects of a metalloporphyrinic peroxynitrite decomposition catalyst in burn and smoke inhalation injury. Am J Physiol Lung Cell Mol Physiol 300: L167–L175.
58. Lee HS, Lee NC, Kouprina N, Kim JH, Kagansky A, Bates S et al. (2016). Effects of anticancer drugs on chromosome instability and new clinical implications for tumor-suppressing therapies. Cancer Res 76: 902–911.
59. Liaudet L, Pacher P, Mabley JG, Virág L, Soriano FG, Haskó G 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: 372–377.
60. Liu SB, Liu J, Liu DW, Wang XT, Yang RL (2015). Inhibition of poly-(ADP-ribose) polymerase protects the kidney in a canine model of endotoxic shock. Nephron 130: 281–292.
61. Luo X, Kraus WL (2012). On PAR with PARP: cellular stress signaling through poly(ADP-ribose) and PARP-1. Genes Dev 26: 417–432.
62. Mabley JG, Horváth EM, Murthy KG, Zsengellér Z, Vaslin A, Benko R et al. (2005). Gender differences in the endotoxin-induced inflammatory and vascular responses: potential role of poly(ADP-ribose) polymerase activation. J Pharmacol Exp Ther 315: 812–820.
63. McCullough LD, Zeng Z, Blizzard KK, Debchoudhury I, Hurn PD (2005). Ischemic nitric oxide and poly (ADP-ribose) polymerase-1 in cerebral ischemia: male toxicity, female protection. J Cereb Blood Flow Metab 25: 502–512.
64. McGrath JC, Lilley E (2015). Implementing guidelines on reporting research using animals (ARRIVE etc.): new requirements for publication in BJP. Br J Pharmacol 172: 3189–3193.
65. Mecott GA, Al-Mousawi AM, Gauglitz GG, Herndon DN, Jeschke MG (2010). The role of hyperglycemia in burned patients: evidence-based studies. Shock 33: 5–13.
66. Ogunbileje JO, Porter C, Herndon DN, Chao T, Abdelrahman DR, Papadimitriou A et al. (2016). Hypermetabolism and hypercatabolism of skeletal muscle accompany mitochondrial stress following severe burn trauma. Am J Physiol Endocrinol Metab 311: E436–E448.
67. Oláh G, Finnerty CC, Sbrana E, Elijah I, Gerö D, Herndon DN et al. (2011). Increased poly(ADP-ribosyl)ation in skeletal muscle tissue of pediatric patients with severe burn injury: prevention by propranolol treatment. Shock 36: 18–23.
68. Oláh G, Szczesny B, Brunyánszki A, López-García IA, Gerö D, Radák Z et al. (2015). Differentiation-associated downregulation of poly(ADP-ribose) polymerase-1 expression in myoblasts serves to increase their resistance to oxidative stress. PLoS One 10: e0134227.
69. Oumouna M, Datta R, Oumouna-Benachour K, Suzuki Y, Hans C, Matthews K et al. (2006). Poly(ADP-ribose) polymerase-1 inhibition prevents eosinophil recruitment by modulating Th2 cytokines in a murine model of allergic airway inflammation: a potential specific effect on IL-5. J Immunol 177: 6489–6496.
70. Pacher P, Szabo C (2008). Role of the peroxynitrite-poly(ADP-ribose) polymerase pathway in human disease. Am J Pathol 173: 2–13.
71. Pang J, Cui J, Gong H, Xi C, Zhang TM (2015). Effect of NAD on PARP-mediated insulin sensitivity in oleic acid treated hepatocytes. J Cell Physiol 230: 1607–1613.
72. Porter C, Tompkins RG, Finnerty CC, Sidossis LS, Suman OE, Herndon DN (2016). The metabolic stress response to burn trauma: current understanding and therapies. Lancet 388: 1417–1426.
73. Pyriochou A, Olah G, Deitch EA, Szabó C, Papapetropoulos A (2008). Inhibition of angiogenesis by the poly(ADP-ribose) polymerase inhibitor PJ-34. Int J Mol Med 22: 113–118.
74. Rae L, Fidler P, Gibran N (2016). The physiologic basis of burn shock and the need for aggressive fluid resuscitation. Crit Care Clin 32: 491–505.
75. Rajesh M, Mukhopadhyay P, Godlewski G, Bátkai S, Haskó G, Liaudet L et al. (2006). Poly(ADP-ribose)polymerase inhibition decreases angiogenesis. Biochem Biophys Res Commun 350: 1056–1062.
76. Ray JJ, Meizoso JP, Allen CJ, Teisch LF, Yang EY, Foong HY et al. (2016). Admission hyperglycemia predicts infectious complications after burns. J Burn Care Res in press.
77. Rosenthal MD, Moore FA (2015). Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): A new phenotype of multiple organ failure. J Adv Nutr Hum Metab 1: e784.
78. Sarras MP Jr, Mason S, McAllister G, Intine RV (2014). Inhibition of poly-ADP ribose polymerase enzyme activity prevents hyperglycemia-induced impairment of angiogenesis during wound healing. Wound Repair Regen 22: 666–670.
79. Schraufstatter IU, Hyslop PA, Hinshaw DB, Spragg RG, Sklar LA, Cochrane CG (1986). Hydrogen peroxide-induced injury of cells and its prevention by inhibitors of poly(ADP-ribose) polymerase. Proc Natl Acad Sci U S A 83: 4908–4912.
80. Shall S (1983). ADP-ribosylation, DNA repair, cell differentiation and cancer. Princess Takamatsu Symp 13: 3–25.
81. Shimoda K, Murakami K, Enkhbaatar P, Traber LD, Cox RA, Hawkins HK et al. (2003). Effect of poly(ADP ribose) synthetase inhibition on burn and smoke inhalation injury in sheep. Am J Physiol Lung Cell Mol Physiol 285: L240–L249.
82. Sims JL, Berger SJ, Berger NA (1983). Poly(ADP-ribose) polymerase inhibitors preserve nicotinamide adenine dinucleotide and adenosine 5'-triphosphate pools in DNA-damaged cells: mechanism of stimulation of unscheduled DNA synthesis. Biochem 22: 5188–5194.
83. Soriano FG, Liaudet L, Szabó E, Virág L, Mabley JG, Pacher P et al. (2002). Resistance to acute septic peritonitis in poly(ADP-ribose) polymerase-1-deficient mice. Shock 17: 286–292.
84. Soriano FG, Nogueira AC, Caldini EG, Lins MH, Teixeira AC, Cappi SB et al. (2006). Potential role of poly(adenosine 5'-diphosphate-ribose) polymerase activation in the pathogenesis of myocardial contractile dysfunction associated with human septic shock. Crit Care Med 34: 1073–1079.
85. Soriano FG, Virág L, Jagtap P, Szabó E, Mabley JG, Liaudet L et al. (2001). Diabetic endothelial dysfunction: the role of poly(ADP-ribose) polymerase activation. Nat Med 7: 108–113.
86. Southan C, Sharman JL, Benson HE, Faccenda E, Pawson AJ, Alexander SP et al. (2016). The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. Nucl Acids Res 44: D1054–D1068.
87. Sui H, Shi C, Yan Z, Li H (2015). Combination of erlotinib and a PARP inhibitor inhibits growth of A2780 tumor xenografts due to increased autophagy. Drug Des Devel Ther 9: 3183–3190.
88. Szabo C, Zingarelli B, O'Connor M, Salzman 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 U S A 93: 1753–1758.
89. Szabo C, Haskó G, Zingarelli B, Németh ZH, Salzman AL, Kvetan V et al. (1997). Isoproterenol regulates tumour necrosis factor, interleukin-10, interleukin-6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia. Immunology 90: 95–100.
90. Szabo C (2007). Poly (ADP-ribose) polymerase activation and circulatory shock. Novartis Found Symp 280: 92–103.
91. Szczesny B, Brunyánszki A, Ahmad A, Oláh G, Porter C, Toliver-Kinsky T et al. (2015). Time-dependent and organ-specific changes in mitochondrial function, mitochondrial DNA integrity, oxidative stress and mononuclear cell infiltration in a mouse model of burn injury. PLoS One 10: e0143730.
92. Teng F, Zhu L, Su J, Zhang X, Li N, Nie Z et al. (2016). Neuroprotective effects of poly(ADP-ribose) polymerase inhibitor olaparib in transient cerebral ischemia. Neurochem Res 41: 1516–1526.
93. To C, Kim EH, Royce DB, Williams CR, Collins RM, Risingsong R et al. (2014). The PARP inhibitors, veliparib and olaparib, are effective chemopreventive agents for delaying mammary tumor development in BRCA1-deficient mice. Cancer Prev Res (Phila) 7: 698–707.
94. Yang Z, Zingarelli B, Szabo C (2000). Effect of genetic disruption of poly (ADP-ribose) synthetase on delayed production of inflammatory mediators and delayed necrosis during myocardial ischemia–reperfusion injury. Shock 13: 60–66.
95. Vassallo JD, Janovitz EB, Wescott DM, Chadwick C, Lowe-Krentz LJ, Lehman-McKeeman LD (2009). Biomarkers of drug-induced skeletal muscle injury in the rat: troponin I and myoglobin. Toxicol Sci 111: 402–412.
96. Virág L, Salzman AL, Szabo C (1998). Poly(ADP-ribose) synthetase activation mediates mitochondrial injury during oxidant-induced cell death. J Immunol 161: 3753–3759.
97. Virág L, Szabo C (2002). The therapeutic potential of poly(ADP-ribose) polymerase inhibitors. Pharmacol Rev 54: 375–429.
98. Walko TD 3rd, Di Caro V, Piganelli J, Billiar TR, Clark RS, Aneja RK (2015). Poly(ADP-ribose) polymerase 1-sirtuin 1 functional interplay regulates LPS-mediated high mobility group box 1 secretion. Mol Med 20: 612–624.
99. Wang G, Huang X, Li Y, Guo K, Ning P, Zhang Y (2013). PARP-1 inhibitor, DPQ, attenuates LPS-induced acute lung injury through inhibiting NF-κB-mediated inflammatory response. PLoS One 8: e79757.
100. Xu JC, Fan J, Wang X, Eacker SM, Kam TI, Chen L et al. (2016). Cultured networks of excitatory projection neurons and inhibitory interneurons for studying human cortical neurotoxicity. Sci Transl Med 8: 333ra48.
101. Yamashita S, Tanaka M, Sato T, Ida C, Ohta N, Hamada T et al. (2016). Effect of mild temperature shift on poly(ADP-ribose) and γH2AX levels in cultured cells. Biochem Biophys Res Commun 476: 594–599.
102. Zaalishvili G, Zaldastanishvili E, Karapetian M, Zaalishvili T (2012). Increased PARP-1 levels in nuclear matrix isolated from heat shock treated rat liver. Biochem (Mosc) 77: 105–110.
103. Zaremba T, Thomas HD, Cole M, Coulthard SA, Plummer ER, Curtin NJ (2011). Poly(ADP-ribose) polymerase-1 (PARP-1) pharmacogenetics, activity and expression analysis in cancer patients and healthy volunteers. Biochem J 436: 671–679.
104. Zhang J, Dawson VL, Dawson TM, Snyder SH (1994). Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. Science 263: 687–689.
105. Zhang L, Yao J, Wang X, Li H, Liu T, Zhao W (2015). Poly (ADP-ribose) synthetase inhibitor has a heart protective effect in a rat model of experimental sepsis. Int J Clin Exp Pathol 8: 9824–9835.
106. Zhou X, Patel D, Sen S, Shanmugam V, Sidawy A, Mishra L et al. (2016). Poly-ADP-ribose polymerase inhibition enhances ischemic and diabetic wound healing by promoting angiogenesis. J Vasc Surg in press.
107. Zingarelli B, O'Connor M, Wong H, Salzman AL, Szabó C (1996). Peroxynitrite-mediated DNA strand breakage activates poly-adenosine diphosphate ribosyl synthetase and causes cellular energy depletion in macrophages stimulated with bacterial lipopolysaccharide. J Immunol 156: 350–358.