Ukr.Biochem.J. 2013; Volume 85, Issue 1, Jan-Feb, pp. 62-70


Influence of poly(ADP-ribose)polymerase inhibitors on some parameters of oxidative stress in blood leukocytes of rats with experimental diabetes

M. M. Guzyk1, K. O. Dyakun1, L. V. Yanitska2, Т. М. Kuchmerovska1

1Palladin Institute of Biochemistry, National Academy of Science of Ukraine, Kyiv;
2O. O. Bogomolets’ National Medical University, Kyiv, Ukraine;

The study was undertaken to investigate the influence of specific inhibitors of poly(ADP-ribose)polymerase-1 (PARP-1), in particular nicotinamide and 1,5-isoqinolinediol on white blood cells of rats with diabetes. Using the fluorescent probe 2′,7′-dichlorodihydrofluorescein diacetate ROS production in leukocytes was asseced. It was found that the development of streptozotocin-induced diabetes was accompanied by an intensification of oxidative stress and a significant decrease in via­bility of blood leukocytes as compared to control animals. Administration of PARP-1 inhibitors prevented the development of oxidative stress in leukocytes and increased their viability. It was shown a reduction of superoxide dismutase activi­ty in serum in diabetes. Investigated PARP-1 inhibitors had no effect on the activity of superoxide dismutase and glucose levels in the blood. The findings­ suggest the intensification of oxidative stress in leukocytes of diabetic animals and the ability of nicotinamide and 1,5-isoqinolinediol to prevent its development depending on the features of their structure.

Keywords: , , , , ,


  1. Hossain P, Kawar B, El Nahas M. Obesity and diabetes in the developing world–a growing challenge. N Engl J Med. 2007 Jan 18;356(3):213-5. PubMed, CrossRef
  2. Shaw JE, Sicree RA, Zimmet PZ. Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract. 2010 Jan;87(1):4-14. PubMed, CrossRef
  3. Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25. PubMed, CrossRef
  4. Gillespie KM. Type 1 diabetes: pathogenesis and prevention. Can Med Assoc J. 2006 Jul 18;175(2):165-70. PubMed, PubMedCentral, CrossRef
  5. Gehrmann W, Elsner M, Lenzen S. Role of metabolically generated reactive oxygen species for lipotoxicity in pancreatic β-cells. Diabetes Obes Metab. 2010 Oct;12 Suppl 2:149-58. Review. PubMed, CrossRef
  6. Maiese K, Morhan SD, Chong ZZ. Oxidative stress biology and cell injury during type 1 and type 2 diabetes mellitus. Curr Neurovasc Res. 2007 Feb;4(1):63-71. Review. PubMed, PubMed, CrossRef
  7. Lin JH, Walter P, Yen TS. Endoplasmic reticulum stress in disease pathogenesis. Annu Rev Pathol. 2008;3(1):399-425. Review. PubMed, PubMed, CrossRef
  8. Eizirik DL, Cardozo AK, Cnop M. The role for endoplasmic reticulum stress in diabetes mellitus. Endocr Rev. 2008 Feb;29(1):42-61. Review. PubMed, CrossRef
  9. Shurtz-Swirski R, Sela S, Herskovits AT, Shasha SM, Shapiro G, Nasser L, Kristal B. Involvement of peripheral polymorphonuclear leukocytes in oxidative stress and inflammation in type 2 diabetic patients. Diabetes Care. 2001 Jan;24(1):104-10. PubMed, CrossRef
  10. Rosenberg DE, Jabbour SA, Goldstein BJ. Insulin resistance, diabetes and cardiovascular risk: approaches to treatment. Diabetes Obes Metab. 2005 Nov;7(6):642-53. Review. PubMed, CrossRef
  11. Molteni R, Fabbri M, Bender JR, Pardi R. Pathophysiology of leukocyte-tissue interactions. Curr Opin Cell Biol. 2006 Oct;18(5):491-8. Review. PubMed, CrossRef
  12. Bertoni AG, Saydah S, Brancati FL. Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care. 2001 Jun;24(6):1044-9. PubMed, CrossRef
  13. Diefenbach J, Bürkle A. Poly-ADP-ribosylation in health and disease. Cell Mol Life Sci. 2005 Apr;62(7-8):721-30. Review. PubMed, CrossRef
  14. Bass DA, Parce JW, Dechatelet LR, Szejda P, Seeds MC, Thomas M. Flow cytometric studies of oxidative product formation by neutrophils: a graded response to membrane stimulation. J Immunol. 1983 Apr;130(4):1910-7. PubMed
  15. Coder DM. Assessment of cell viability. Curr Protoc Cytom. 1997;15:9.2.1-9.2.2.
  16. Ewing JF, Janero DR. Microplate superoxide dismutase assay employing a nonenzymatic superoxide generator. Anal Biochem. 1995 Dec 10;232(2):243-8. PubMed, CrossRef
  17. Otton R, Soriano FG, Verlengia R, Curi R. Diabetes induces apoptosis in lymphocytes. J Endocrinol. 2004 Jul;182(1):145-56. PubMed, CrossRef
  18. Cuzzocrea S. Shock, inflammation and PARP. Pharmacol Res. 2005 Jul;52(1):72-82. Review. PubMed, CrossRef
  19. Evgenov OV, Liaudet L. Role of nitrosative stress and activation of poly(ADP-ribose) polymerase-1 in cardiovascular failure associated with septic and hemorrhagic shock. Curr Vasc Pharmacol. 2005 Jul;3(3):293-9. Review. PubMed, CrossRef
  20. Virág L. Structure and function of poly(ADP-ribose) polymerase-1: role in oxidative stress-related pathologies. Curr Vasc Pharmacol. 2005 Jul;3(3):209-14. Review. PubMed, CrossRef
  21. Merzouk S, Hichami A, Sari A, Madani S, Merzouk H, Yahia Berrouiguet A, Lenoir-Rousseaux JJ, Chabane-Sari N, Khan NA. Impaired oxidant/antioxidant status and LDL-fatty acid composition are associated with increased susceptibility to peroxidation of LDL in diabetic patients. Gen Physiol Biophys. 2004 Dec;23(4):387-99. PubMed
  22. Bonnefont-Rousselot D, Bastard JP, Jaudon MC, Delattre J. Consequences of the diabetic status on the oxidant/antioxidant balance. Diabetes Metab. 2000 May;26(3):163-76. Review. PubMed
  23. Kuchmerovska T, Shymanskyy I, Donchenko G, Kuchmerovskyy M, Pakirbaieva L, Klimenko A. Poly(ADP-ribosyl)ation enhancement in brain cell nuclei is associated with diabetic neuropathy. J Diabetes Complications. 2004 Jul-Aug;18(4):198-204. PubMed, CrossRef
  24. Luo J, Nikolaev AY, Imai S, Chen D, Su F, Shiloh A, Guarente L, Gu W. Negative control of p53 by Sir2alpha promotes cell survival under stress. Cell. 2001 Oct 19;107(2):137-48. PubMed, CrossRef
  25. Chong ZZ, Lin SH, Li F, Maiese K. The sirtuin inhibitor nicotinamide enhances neuronal cell survival during acute anoxic injury through AKT, BAD, PARP, and mitochondrial associated “anti-apoptotic” pathways. Curr Neurovasc Res. 2005 Oct;2(4):271-85. PubMed, PubMedCentral, CrossRef
  26. Southan GJ, Szabó C. Poly(ADP-ribose) polymerase inhibitors. Curr Med Chem. 2003 Feb;10(4):321-40. Review. PubMed, CrossRef
  27. Li F, Drel VR, Szabó C, Stevens MJ, Obrosova IG. Low-dose poly(ADP-ribose) polymerase inhibitor-containing combination therapies reverse early peripheral diabetic neuropathy. Diabetes. 2005 May;54(5):1514-22. PubMed, CrossRef
  28. Martin A, Komada MR, Sane DC. Abnormal angiogenesis in diabetes mellitus. Med Res Rev. 2003 Mar;23(2):117-45. Review. PubMed, CrossRef
  29. Rajesh M, Mukhopadhyay P, Godlewski G, Bátkai S, Haskó G, Liaudet L, Pacher P. Poly(ADP-ribose)polymerase inhibition decreases angiogenesis. Biochem Biophys Res Commun. 2006 Dec 1;350(4):1056-62. Epub 2006 Oct 9. PubMed, PubMedCentral, CrossRef
  30. Dedon PC, Tannenbaum SR. Reactive nitrogen species in the chemical biology of inflammation. Arch Biochem Biophys. 2004 Mar 1;423(1):12-22. Review. PubMed, CrossRef
  31. Korhonen R, Lahti A, Kankaanranta H, Moilanen E. Nitric oxide production and signaling in inflammation. Curr Drug Targets Inflamm Allergy. 2005 Aug;4(4):471-9. Review. PubMed, CrossRef
  32. Olszanecki R, Gebska A, Jawień J, Jakubowski A, Korbut R. Inhibition of NOS-2 induction in LPS-stimulated J774.2 cells by 1, 5-isoquinolinediol, an inhibitor of PARP. J Physiol Pharmacol. 2006 Mar;57(1):109-17. PubMed
  33. Young LH, Ikeda Y, Lefer AM. Protein kinase inhibition exerts cardioprotective effects in myocardial ischemia/reperfusion via inhibition of superoxide release. Methods Find Exp Clin Pharmacol. 2001 Apr;23(3):107-14. PubMed, CrossRef

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