Українська Русский English

ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)
DOI: https://doi.org/10.15407/fz

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2017; 63(1): 43-50


THE EFFECT OF OF POLY(ADP-RIBOSE) POLYMERASE INHIBITOR 4-HYDROXYQUINAZOLINE ON DEATH OF IMMUNE CELLS UNDER IMMUNE COMPLEX-MEDIATED INJURY IN MICE

N.G. Grushka

    О.О. Bogomoletz Institute of Physiology of the National Academy of Sciences of Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz63.01.043

Abstract

The influence of poly(ADP-ribose) polymerase (PARP) inhibitor 4-hydroxyquinazoline (4-HQ) on the level of DNA damage and on the death of thymic and lymph node cells in mouse model of immune complex injury was investigated to reveal its possible cytoprotective effect. As shown by comet assay, DNA damage index of immune cells was increased 4,0 times in mice with immune complex-mediated pathology induced by a long-term immunization of CBA mice with bovine serum albumin (BSA), Р<0,001. The percentage of thymic cells with strong DNA damage was increased to 77 % under immunization (compared to 1,5 % in control mice) and the percentage of such cells from lymph nodes was increased to 80 % (compared to 0 % in control), in both cases P< 0,001. Genotoxic stress was reduced by treatment of immunized mice with 4-HQ: the percentage of lymphocytes with strong DNA damage was significantly decreased that promoted increase in the amount of cells having intact DNA. PARP inhibition exerted a strong cytoprotective effect: viability of thymus and lymph node cells was increased mainly due to reduced level of necrosis. So, our results suggest that PARP may be involved in thymic and lymph node cell damage in immune complex mediated pathology and give evidence that inhibition of this enzyme may constitute a perspective target in immune complex diseases prevention and therapy.

Keywords: https://10.15407/fz63.01.043

References

  1. Makogon NV, Alexeyeva IM. Poly(ADP-ribose) polymerase (PARP): physiological and pathological roles. Fiziol Zh. 2012; 58 (3): 95-112.[Ukrainian]. CrossRef  PubMed
  2.  
  3. Drel VR, Sybirna NO. Nephroprotective effect of grape wine in the rat with experimental diabetes millitus. Stud Biolog. 2009; 3 (3): 59– 68.
  4.  
  5. Bao Z, Xiong J, Li W, Chen Z, Shen H, Ying S. Genomic instability in chronic airway inflammatory diseases. Biomed J. 2015; 38(2):117-24. CrossRef PubMed
  6.  
  7. Toth-Zsamboki E, Horvath E, Vargova K et al. Activation of poly(ADP-ribose) polymerase by myocardial ischemia and coronary reperfusion in human circulating leukocytes. Mol Med. 2006;12(9-10):221-8. CrossRef PubMed PubMedCentral
  8.  
  9. Jog NR, Dinnall JA, Gallucci S, Madaio MP, Caricchio R. Poly(ADP-ribose) polymerase-1 regulates the progression of autoimmune nephritis in males by inducing necrotic cell death and modulating inflammation. J Immunol. 2009; 182(11):7297-306. CrossRef PubMed PubMedCentral
  10.  
  11. Bai P. Role of poly(ADP-ribose) polymerases in the regulation of inflammatory processes. FEBS Lett. 2012; 586 (21): 3771–7. CrossRef PubMed
  12.  
  13. Gonzalez-Rey E, Martínez-Romero R, O'Valle F, AguilarQuesada R, Conde C, Delgado M, Oliver FJ. Therapeutic effect of a poly(ADP-ribose) polymerase-1 inhibitor on experimental arthritis by downregulating inflammation and Th1 response. PLoS ONE. 2007; 2 (10): e1071. CrossRef PubMed PubMedCentral
  14.  
  15. Grushka N, Makogon N, Pavlovych S, Bryzgina T, Martynova T, Sukhina V, Yanchiy R. Poly (ADP-ribose) polymerase inhibitor 4-hydroxyquinazoline exerts a protective effect against concanavalin A-induced hepatitis in mice. Health Sci. 2014;3(11): 463-8.
  16.  
  17. Wang Y, Dawson VL, Dawson TH. Poly(ADP-ribose) signals to mitochondrial AIF: a key event in parthanatos. Exp Neurol. 2009; 218 (2);193–202. CrossRef PubMed PubMedCentral
  18.  
  19. Fuerst M. More than a handful of PARP inhibitors in development to treat hereditary breast cancer. Oncol Tim. 2014; 36 (2): 50-1. CrossRef  
  20. Lytvynenko AP, Pavlovych SI, Makogon NV, Yanchiy RI Effects of inhibitor of poly (ADP- ribose)polymerase on the deposition of immune complexes and uterine contractility under systemic immune complex disorders in mice. Med Hydrol Rehabil. 2014; 12 (1/4): 15-21.
  21.  
  22. Afanasieva K, Zazhytska M, Sivolob A. Kinetics of comet formation in single-cell gel electrophoresis: Loops and fragments . Electrophoresis. 2010; 31: 512-19. CrossRef PubMed
  23.  
  24. Collins AR. The comet assay for DNA damage and repair: principles, applications, and limitations. Mol Biotechnol. 2004;26(3):249-61. CrossRef  
  25. Sorochinska J, Mikhailenko V. Application of the comet assay for the DNA damage assessment caused by different inveronmental agents. Oncology. 2008; 10 (3): 303-8.
  26.  
  27. Kamboj A, Lu P, Cossoy MB. Poly(ADP-ribose) polymerase 2 contributes to neuroinflammation and neurological dysfunction in mouse experimental autoimmune encephalomyelitis. J Neuroinflam. 2013; 10: 49–58. CrossRef PubMed PubMedCentral
  28.  
  29. Ahmad SF, Zoheir KM, Bakheet SA, Ashour AE, Attia SM. Poly(ADP-ribose) polymerase-1 inhibitor modulates T regulatory and IL-17 cells in the prevention of adjuvant induced arthritis in mice model. Cytokine. 2014; 68(2): 76–85. CrossRef PubMed
  30.  
  31. Heaton PR, Ransley R, Charlton CJ, Mann SJ, Stevenson J, Smith BH, Rawlings JM, Harper EJ. Application of single-cell gel electrophoresis (comet) assay for assessing levels of DNA damage in canine and feline leukocytes. J Nutr. 2002;132(6 Suppl 2):1598-603.
  32.  
  33. Kaminskyy VO, Lutsik MD, Stoika RS. Comet assay of dna fragmentation: modification of silver staining for obtaining permanent preparations. Ukr Biochem. 2005; 77 (6): 105-7.
  34.  
  35. Chopyak V, Valchuk IV, Hayduchok IG. Hiperimunokompleksnyy syndrome in experiment and clinic. Bull Sci Res. 2007; 1: 5-8.
  36.  
  37. Pavlovych SI, Lytvynenko AP, Makogon NV, Martynova TV, Bryzgina TM, Yanchiy RI, Cukhina VS, Shepel OA, Voznesenska TYu, Blashkiv TV, Getmanets AV. Immunomorphological characterization of mouse model of a systemic immune complexes mediated pathology. Rep Morphol. 2014; 8 (2):496-500.
  38.  
  39. Jancar S, Sánchez Crespo M. Immune complex-mediated tissue injury: a multistep paradigm. Trends Immunol. 2005;26(1):48-55. CrossRef PubMed
  40.  
  41. Kirkland J. Poly ADP-ribose polymerase-1 and health. Exp Biol Med. 2010; 235 (5):561 –68. CrossRef PubMed
  42.  
  43. Besson V.C. Drug targets for traumatic brain injury from poly(ADP-ribose) polymerase pathway modulation. Br J Pharmacol. 2009; 157: 696-704. CrossRef PubMed PubMedCentral
  44.  
  45. Banasik M, Stedeford T, Strosznajder RP. Natural inhibitors of poly(ADP-ribose) polymerase-1. Mol Neurobiol. 2012; 46 (1): 55-63. CrossRef PubMed

© National Academy of Sciences of Ukraine, Bogomoletz Institute of Physiology, 2014-2019.