World Journal of Dentistry

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VOLUME 12 , ISSUE 6 ( November-December, 2021 ) > List of Articles


Effect of Low-dose Aspirin on Neutrophil Apoptosis in Periodontitis: An Immunohistochemical Study

Shivanaikar Sachin, Faizuddin Mohamed, Bhat Kishore, Vijaya Kumar, D'souza Neevan, Aruna Ganganna

Keywords : Apoptosis, Aspirin, Neutrophil, Periodontitis

Citation Information : Sachin S, Mohamed F, Kishore B, Kumar V, Neevan D, Ganganna A. Effect of Low-dose Aspirin on Neutrophil Apoptosis in Periodontitis: An Immunohistochemical Study. World J Dent 2021; 12 (6):441-445.

DOI: 10.5005/jp-journals-10015-1879

License: CC BY-NC 4.0

Published Online: 24-11-2021

Copyright Statement:  Copyright © 2021; The Author(s).


Aim and objective: A growing body of research today suggests that periodontitis is due to the failure of resolution pathways to restore homeostasis. Resolution is an active phenomenon of suppressing inflammation once its main objective of eliminating pathogens is achieved. Neutrophil apoptosis is an important step in promoting resolution. In chronic periodontitis, neutrophils linger for a long time in inflamed connective tissue and cause tissue destruction. Aspirin, a widely used anti-inflammatory and anti-thrombogenic drug, is known to cause neutrophil apoptosis by synthesizing aspirin-triggered lipoxin (15epiLXA4) a potent pro-resolving lipid mediator. This immunohistochemical investigation is designed to study the effect of low-dose aspirin therapy on neutrophil apoptosis in the gingival biopsies of patients suffering from periodontitis. Materials and methods: The study population consisted of 30 periodontitis patients who were divided into two groups of 15 each as test group and control group. Test group patients were on low-dose aspirin (75 mg/150 mg) therapy for clinical management of class 1 and class 2 functional capacity cardiovascular disease. Periodontal parameters like plaque index (PI), bleeding index (BI), probing pocket depth (PPD), and clinical attachment loss (CAL) were recorded, gingival biopsies were obtained from all patients for quantitative analysis of neutrophil apoptosis by immunohistochemistry using p53 as a marker of apoptosis. Chi-square/Fisher's exact test was used to find the significance of study parameters on a categorical scale between two groups. Results: Results indicated that there was a decrease in PPD and CAL and a marginal increase in neutrophil apoptosis in the test group in comparison with a control group. Conclusion: Low-dose aspirin therapy may induce neutrophil apoptosis and improve PPD and CAL. Hence, it is presumed that it has the potential to be used as a host-modulating agent in the clinical management of periodontitis. Clinical significance: The low-dose aspirin could be used as a host-modulating agent in the management of periodontitis. Key messages: Increase apoptosis of neutrophils in the gingival biopsies of periodontitis patients who are on long-term low-dose aspirin therapy for CVD indicates that low-dose aspirin could be a potential host modality agent in the treatment of chronic periodontitis.

  1. Cekici A, Kantarci A, Hasturk H, et al. Inflammatory and immune pathways in the pathogenesis of periodontal disease. Periodontol 2000 2014;64(1):57–80. DOI: 10.1111/prd.12002.
  2. Reynolds JJ, Meikle MC. Mechanisms of connective tissue matrix destruction in periodontitis. Periodontol 2000 1997;14(1):144–157. DOI: 10.1111/j.1600-0757.1997.tb00195.x.
  3. Ortega-Gómez A, Perretti M, Soehnlein O. Resolution of inflammation: an integrated view. EMBO Molecul Med 2013;5(5):661–674. DOI: 10.1002/emmm.201202382.
  4. Sugimoto MA, Sousa LP, Pinho V, et al. Resolution of inflammation: what controls its onset? Front Immunol 2016;7:160. DOI: 10.3389/fimmu.2016.00160.
  5. Milot E, Filep JG. Regulation of neutrophil survival/apoptosis by Mcl-1. Scienti World J 2011. 11. DOI: 10.1100/2011/131539.
  6. El Kebir D, Filep JG. Modulation of neutrophil apoptosis and the resolution of inflammation through β2 integrins. Front Immunol 2013;4:60. DOI: 10.3389/fimmu.2013.00060.
  7. Savill J, Fadok V. Corpse clearance defines the meaning of cell death. Nature 2000;407(6805):784–788. DOI: 10.1038/35037722.
  8. Gamonal J, Sanz M, O'Connor A, et al. Delayed neutrophil apoptosis in chronic periodontitis patients. J Clin Periodontol 2003;30(7):616–623. DOI: 10.1034/j.1600-051x.2003.00350.x.
  9. Elmore S. Apoptosis: a review of programmed cell death. Toxicol Pathol 2007;35(4):495–516. DOI: 10.1080/01926230701320337.
  10. Leist M, Jaattela M. Four deaths and a funeral: from caspases to alternative mechanisms. Nat Rev Mol Cell Biol 2001;2(8):589–598. DOI: 10.1038/35085008.
  11. Mariggiò MA, Guida L, Laforgia A, et al. Nicotine effects on polymorphonuclear cell apoptosis and lipopolysaccharide-induced monocyte functions. A possible role in periodontal disease? J Periodontal Res 2001;36(1):32–39. DOI: 10.1034/j.1600-0765.2001.00301.x.
  12. Renehan AG, Booth C, Potten CS. What is apoptosis, and why is it important? BMJ 2001;322(7301):1536–1540. DOI: 10.1136/bmj.322.7301.1536.
  13. Bulut S, Uslu H, Handan B, et al. Expression of caspase-3, p53 and Bcl-2 in generalized aggressive periodontitis. Head Face Med 2006;2(1):17. DOI: 10.1186/1746-160X-2-17.
  14. Mitchell JA, Akarasereenont P, Thiemermann C, et al. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci 1993;90(24):11693–11697. DOI: 10.1073/pnas.90.24.11693.
  15. Serhan CN. Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostagland, Leukotri Essent Fatty Acids 2005;73(3-4):141–162. DOI: 10.1016/j.plefa.2005.05.002.
  16. Van Dyke TE. Control of inflammation and periodontitis. Periodontol 2000 2007;45(1):158–166. DOI: 10.1111/j.1600-0757.2007.00229.x.
  17. Drouganis A, Hirsch R. Low-dose aspirin therapy and periodontal attachment loss in ex- and non-smokers. J Clin Periodontol 2001;28(1):38–45. DOI: 10.1034/j.1600-051x.2001.280106.x.
  18. Faizuddin M, Tarannum F, Korla N, et al. Association between long-term aspirin use and periodontal attachment level in humans: a cross-sectional investigation. Aust Dent J 2012;57(1):45–50. DOI: 10.1111/j.1834-7819.2011.01650.x.
  19. Shivanaikar SS, Faizuddin M, Bhat K. Effect of smoking on neutrophil apoptosis in chronic periodontitis: an immunohistochemical study. Indian J Dent Res 2013;24(1):147. DOI: 10.4103/0970-9290.114935.
  20. Jarnbring F, Somogyi E, Dalton J, et al. Quantitative assessment of apoptotic and proliferative gingival keratinocytes in oral and sulcular epithelium in patients with gingivitis and periodontitis. J Clin Periodontol 2002;29(12):1065–1071. DOI: 10.1034/j.1600-051x.2002.291203.x.
  21. Paquette DW, Williams RC. Modulation of host inflammatory mediators as a treatment strategy for periodontal diseases. Periodontol 2000 2000;24(1):239–252. DOI: 10.1034/j.1600-0757.2000.2240112.x.
  22. Hasturk H, Kantarci A. Activation and resolution of periodontal inflammation and its systemic impact. Periodontol 2000 2015;69(1):255–273. DOI: 10.1111/prd.12105.
  23. Selders GS, Fetz AE, Radic MZ, et al. An overview of the role of neutrophils in innate immunity, inflammation and host-biomaterial integration. Regenerat Biomater 2017;4(1):55–68. DOI: 10.1093/rb/rbw041.
  24. Dennis EA, Norris PC. Eicosanoid storm in infection and inflammation. Nat Rev Immunol 2015;15(8):511–523. DOI: 10.1038/nri3859.
  25. Takano T, Fiore S, Maddox JF, et al. Aspirin-triggered 15-epi-lipoxin A4 (LXA4) and LXA4 stable analogues are potent inhibitors of acute inflammation: evidence for anti-inflammatory receptors. J Experim Med 1997;185(9):1693–1704. DOI: 10.1084/jem.185.9.1693.
  26. Warner TD, Nylander S, Whatling C. Anti-platelet therapy: cyclo-oxygenase inhibition and the use of aspirin with particular regard to dual anti-platelet therapy. Br J Clin Pharmacol 2011;72(4):619–633. DOI: 10.1111/j.1365-2125.2011.03943.x.
  27. Toufektchan E, Toledo F. The guardian of the genome revisited: p53 downregulates genes required for telomere maintenance, DNA repair, and centromere structure. Cancers 2018;10(5):135. DOI: 10.3390/cancers10050135.
  28. Royzman D, Recio L, Badovinac RL, et al. The effect of aspirin intake on bleeding on probing in patients with gingivitis. J Periodontol 2004;75(5):679–684. DOI: 10.1902/jop.2004.75.5.679.
  29. Greenlee-Wacker MC. Clearance of apoptotic neutrophils and resolution of inflammation. Immunolog Rev 2016;273(1):357–370. DOI: 10.1111/imr.12453.
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