Skip to main content
SpringerLink
Log in

Multi-target Approach for Oxidative Stress Modulation by Aspirin, Salicylates and Other NSAIDs: Clinical Implications in Atherosclerosis

  • Chapter
  • First Online:
Modulation of Oxidative Stress in Heart Disease

  • 340 Accesses

Abstract

Atherosclerosis is a multifactorial process with oxidative stress being implicated in its pathophysiology. Aspirin and salicylates have pleiotropic effects. Among these pleiotropic effects, modulation of stress response by salicylates is quite interesting. Salicylates modulate stress response in prokaryotic organisms as well as in eukaryotic cells. Modulation of stress response by salicylates is due to the effect of salicylates on cell signalling pathways as well as to the pro-oxidant–antioxidant effects of salicylates. Aspirin and salicylates target oxidative stress in atherosclerosis through multiple antiplatelet-independent mechanisms of action, including scavenging of reactive oxygen species, enhancement of nitrous oxide release, inhibition of superoxide anion release, induction of GSH-dependent antioxidant mechanisms and epigenetic regulation of antioxidant enzymes. Thus, aspirin and salicylates are promising multi-target agents against oxidative stress implicated in atherosclerosis. Based on this evidence, the role of aspirin in the primary prevention of atherosclerosis should be revisited.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Cervadoro A, Palomba R, Vergaro G et al (2018) Targeting inflammation with nanosized drug delivery platforms in cardiovascular diseases: immune cell modulation in atherosclerosis. Front Bioeng Biotechnol 6:177. https://doi.org/10.3389/fbioe.2018.00177. eCollection 2018

    Article  PubMed  PubMed Central  Google Scholar 

  2. Uchiyama S (2017) Aspirin for primary stroke prevention in elderly patients with vascular risk factors. J Gen Fam Med 18:331–335

    PubMed  PubMed Central  Google Scholar 

  3. Lee SK, Khambhati J, Varghese T et al (2017) Comprehensive primary prevention of cardiovascular disease in women. Clin Cardiol 40:832–838

    PubMed  PubMed Central  Google Scholar 

  4. Saito Y, Okada S, Ogawa H et al (2017) Low-dose aspirin for primary prevention of cardiovascular events in patients with type 2 diabetes mellitus: 10-year follow-up of a randomized controlled trial. Circulation 135:659–670

    CAS  PubMed  Google Scholar 

  5. Ogawa H, Nakayama M, Morimoto T et al (2008) Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA 300:2134–2141

    CAS  PubMed  Google Scholar 

  6. Wolff T1, Miller T, Ko S (2009) Aspirin for the primary prevention of cardiovascular events: an update of the evidence for the U.S. preventive services task force. Ann Intern Med Mar 150:405–410

    Google Scholar 

  7. Yiannakopoulou E (2011) Hemoptysis under diclofenac and antiplatelet doses of aspirin. Pharmacology 87:1–4

    CAS  PubMed  Google Scholar 

  8. Yiannakopoulou E (2005) Cellular mechanisms of adaptation in oxidative stress and in heat shock in Saccharomyces cerevisiae: the effect of antioxidants. Msc thesis for the Msc Medical Biology Medical School and Department of Biology, University of Athens

    Google Scholar 

  9. Yiannakopoulou E (2007) Investigation of the role of salicylates in preconditioning. Final report for postdoctoral research (IKY Scholarship 15109/07.10.2005)

    Google Scholar 

  10. Yiannakopoulou ΕC, Delitheos A, Tiligada E (2005) Dose-dependent effect of non-steroidal anti-inflammatory agents on the cellular stress response. Epitheor Klin Farmacol Farmakokinet 23:39–41

    Google Scholar 

  11. Yiannakopoulou ΕC, Tiligada E (2007) Pharmacological preconditioning in the oxidative stress response of eukaryotic cells: in process method validation. Epitheor Klin Farmacol Farmakokinet 25:30–32

    CAS  Google Scholar 

  12. Yiannakopoulou E (2009) Oxidative stress-antioxidant mechanisms-clinical implications. Arch Greek Med 26:23–35

    Google Scholar 

  13. Yiannakopoulou E (2014) Targeting epigenetic mechanisms and microRNAs by aspirin and other non steroidal anti-inflammatory agents--implications for cancer treatment and chemoprevention. Cell Oncol (Dordr) 37:167–178

    CAS  Google Scholar 

  14. Yiannakopoulou E (2012) Modulation of lymphangiogenesis: a new target for aspirin and other nonsteroidal anti-inflammatory agents? A systematic review. J Clin Pharmacol 52:1749–1754

    CAS  PubMed  Google Scholar 

  15. Yin MJ, Yamamoto Y, Gaynor RB (1999) The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature 396:77–80

    Google Scholar 

  16. Yiannakopoulou E (2003) Quality of diagnosis and treatment of arterial hypertension in Greece. PhD thesis, Medical School University of Athens, Greece

    Google Scholar 

  17. Yiannakopoulou E, Papadopulos IS, Cokkinos DV et al (2005) Adherence to antihypertensive treatment: a critical factor for blood pressure control. Eur J Cardiovasc Prev Rehabil 2005(12):243–249

    Google Scholar 

  18. Lu L, Qin Y, Chen C et al (2018) Beneficial effects exerted by paeonol in the management of atherosclerosis. Oxidative Med Cell Longev 2018:1098617

    Google Scholar 

  19. Υiannakopoulou E, Νikiteas N, Perrea D et al (2012) Pharmacological preconditioning of oxidative stress response: systematic review. Surg Laparosc Endosc Percutan Tech 22:200–204

    Google Scholar 

  20. Yiannakopoulou E, Tiligada E (2009) Preconditioning effect of salicylates against oxidative stress in yeast. J Appl Microbiol 106:903–908

    CAS  PubMed  Google Scholar 

  21. Yiannakopoulou EC, Tiligada E (2006) Acetaminophen modulates the oxidative stress response in eucaryotic cells. Rev Clin Pharmacol Pharmacokinet 20:125–127

    CAS  Google Scholar 

  22. Radimer K, Bindewald B, Hughes J et al Dietary supplement use by US adults: data from the national health and nutrition examination survey, 1999–2000. Am J Epidemiol 160:339–349

    PubMed  Google Scholar 

  23. Kim HJ, Giovannucci E, Rosner B et al (2014) Longitudinal and secular trends in dietary supplement use: nurses’ health study and health professionals follow-up study, 1986–2006. J Acad Nutr Diet 114:436–443

    PubMed  Google Scholar 

  24. Joshipura KJ, Hu FB, Manson JE et al (2001) The effect of fruit and vegetable intake on risk for coronary heart disease. Ann Intern Med 134:1106–1114

    CAS  PubMed  Google Scholar 

  25. Miedema MD, Petrone A, Shikany JM et al (2015) Association of fruit and vegetable consumption during early adulthood with the prevalence of coronary artery calcium after 20 years of follow-up: the coronary artery risk development in young adults (CARDIA) study. Circulation 132:1990–1998

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Christen WG, Gaziano JM, Hennekens CH (2000) Design of physicians’ health study II—a randomized trial of beta-carotene, vitamins E and C, and multivitamins, in prevention of cancer, cardiovascular disease, and eye disease, and review of results of completed trials. Ann Epidemiol 10:125–134

    CAS  PubMed  Google Scholar 

  27. Yiannakopoulou E (2012) Does pharmacodynamic interaction of non enzymatic antioxidants modify response to anti-oxidant therapy in the process of atherosclerosis? J Cardiovasc Pharmacol 17:366–372

    CAS  Google Scholar 

  28. Mohanakumar KP, Muralikrishnan D, Thomas B (2000) Neuroprotection by sodium salicylate against 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine-induced neurotoxicity. Brain Res 864:281–290

    CAS  PubMed  Google Scholar 

  29. Bektaşoğlu B, Ozyürek M, Güçlü K et al (2008) Hydroxyl radical detection with a salicylate probe using modified CUPRAC spectrophotometry and HPLC. Talanta 77:90–97

    PubMed  Google Scholar 

  30. Rivas-Estilla AM, Bryan-Marrugo OL, Trujillo-Murillo K et al (2012) Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells. Am J Physiol Gastrointest Liver Physiol 302:G1264–G7327

    CAS  PubMed  Google Scholar 

  31. Wróbel M, Góralska J, Jurkowska H et al (2017) Similar effect of sodium nitroprusside and acetylsalicylic acid on antioxidant system improvement in mouse liver but not in the brain. Biochimie 135:181–185

    PubMed  Google Scholar 

  32. Gondor OK, Pál M, Darkó É et al (2016) Salicylic acid and sodium salicylate alleviate cadmium toxicity to different extents in maize (Zea mays L.). PLoS One 11:e0160157

    PubMed  PubMed Central  Google Scholar 

  33. Oliveira VC, Constante SAR, Polloni L et al (2018) Protective effect of aspirin against mitomycin C-induced carcinogenicity, assessed by the test for detection of epithelial tumor clones (warts) in Drosophila melanogaster. Drug Chem Toxicol 41:330–33733

    CAS  PubMed  Google Scholar 

  34. Jian Z, Tang L, Yi X et al (2016) Aspirin induces Nrf2-mediated transcriptional activation of haem oxygenase-1 in protection of human melanocytes from H2 O2 -induced oxidative stress. J Cell Mol Med 20:1307–1318

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Bonaterra GA, Heinrich E, Kelber O et al (2010a) Anti-inflammatory effects of the willow bark extract STW 33-I (Proaktiv®) in LPS-activated human monocytes and differentiated macrophages. Phytomedicine 17:1106–1113

    CAS  PubMed  Google Scholar 

  36. Enayat S, Banerjee S (2009) Comparative antioxidant activity of extracts from leaves, bark and catkins of Salix aegyptiaca sp. Food Chem 116:23–28

    CAS  Google Scholar 

  37. Ishikado A, Sono Y, Matsumoto M et al (2013) Willow bark extract increases antioxidant enzymes and reduces oxidative stress through activation of Nrf2 in vascular endothelial cells and Caenorhabditis elegans. Free Radic Biol Med 65:1506–1515

    CAS  PubMed  Google Scholar 

  38. Maniqlia FP, Costa JA (2016) Effects of acetylsalicylic acid usage on inflammatory and oxidative stress markers in hemodialysis patients. Inflammation 9:243–24734

    Google Scholar 

  39. Berg K, Langaas M, Ericsson M et al (2013) Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting. Eur J Cardiothorac Surg 43:1154–1163

    PubMed  Google Scholar 

  40. Berg K, Haaverstad R, Astudillo R et al (2006) Oxidative stress during coronary artery bypass operations: importance of surgical trauma and drug treatment. Scand Cardiovasc J 40:291–297

    CAS  PubMed  Google Scholar 

  41. Grosser N, Abate A, Oberle S et al (2003) Heme oxygenase-1 induction may explain the antioxidant profile of aspirin. Biochem Biophys Res Commun 308:956–960

    CAS  PubMed  Google Scholar 

  42. Grosser N, Schroder H (2003) Aspirin protects endothelial cells from oxidant damage via the nitric oxide-cGMP pathway. Arterioscler Thromb Vasc Biol 23:1345–1351

    CAS  PubMed  Google Scholar 

  43. He B, Zhao S, Zhang W et al (2010) Salicylate prevents hepatic oxidative stress activation caused by short-term elevation of free fatty acids in vivo. Diabetes Res Clin Pract 89:150–156

    CAS  PubMed  Google Scholar 

  44. He B1, Zhao S, Zhang W et al (2010) Effect of sodium salicylate on oxidative stress and insulin resistance induced by free fatty acids. Hepatobiliary Pancreat Dis Int 9:49–53

    CAS  PubMed  Google Scholar 

  45. Wu R, Lamontagne D, de Champlain J (2002) Antioxidative properties of acetylsalicylic acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation 105:387–9235

    CAS  PubMed  Google Scholar 

  46. El MA, Wu R, de Champlain J (2002) Prevention of hypertension, hyperglycemia and vascular oxidative stress by aspirin treatment in chronically glucose-fed rats. J Hypertens 20:1407–1412

    Google Scholar 

  47. Wu R, Laplante MA, De Champlain J (2004) Prevention of angiotensin II-induced hypertension, cardiovascular hypertrophy and oxidative stress by acetylsalicylic acid in rats. J Hypertens 22:793–801

    PubMed  Google Scholar 

  48. Tauseef M, Sharma KK, Fahim M (2007) Aspirin restores normal baroreflex function in hypercholesterolemic rats by its antioxidative action. Eur J Pharmacol 556:136–143

    CAS  PubMed  Google Scholar 

  49. Mei L, Daud MK, Ullah N et al (2015) Pretreatment with salicylic acid and ascorbic acid significantly mitigate oxidative stress induced by copper in cotton genotypes. Environ Sci Pollut Res Int 22:9922–9931

    CAS  PubMed  Google Scholar 

  50. Tauseef M, Shahid M, Sharma KK et al (2008) Antioxidative action of aspirin on endothelial function in hypercholesterolaemic rats. Basic Clin Pharmacol Toxicol 103:314–321

    CAS  PubMed  Google Scholar 

  51. Podhaisky H-P, Abate A, Polte T et al (1997) Aspirin protects endothelial cells from oxidative stress–possible synergism with vitamin E. FEBS Lett 417:349–351

    CAS  PubMed  Google Scholar 

  52. Korkmaz-Icöz S, Atmanli A, Radovits T, Li S et al (2016) Administration of zinc complex of acetylsalicylic acid after the onset of myocardial injury protects the heart by upregulation of antioxidant enzymes. J Physiol Sci 66:113–125

    PubMed  Google Scholar 

  53. Korkmaz S, Atmanli A, Li S, Radovits T et al (2015) Superiority of zinc complex of acetylsalicylic acid to acetylsalicylic acid in preventing postischemic myocardial dysfunction. Exp Biol Med (Maywood) 240:1247–1255

    CAS  Google Scholar 

  54. Amel Zabihi N, Mahmoudabady M, Soukhtanloo M et al (2018) Salix alba attenuated oxidative stress in the heart and kidney of hypercholesterolemic rabbits. Avicenna J Phytomed 8:63–72

    PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biomedical Sciences, Faculty of Health Sciences, University of West Attica, Athens, Greece

    Eugenia Yiannakopoulou

Authors
  1. Eugenia Yiannakopoulou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Eugenia Yiannakopoulou .

Editor information

Editors and Affiliations

  1. Department of Biochemistry and Biophysics, University of Kalyani, Kalyani, West Bengal, India

    Sajal Chakraborti

  2. Institute of Cardiovascular Science, St. Boniface Hospital Research Centre, Winnipeg, MB, Canada

    Naranjan S. Dhalla

  3. Translational Health Science and Technology Institute, Faridabad, Haryana, India

    Madhu Dikshit

  4. Translational Health Science and Technology Institute, Faridabad, Haryana, India

    Nirmal K. Ganguly

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Yiannakopoulou, E. (2019). Multi-target Approach for Oxidative Stress Modulation by Aspirin, Salicylates and Other NSAIDs: Clinical Implications in Atherosclerosis. In: Chakraborti, S., Dhalla, N., Dikshit, M., Ganguly, N. (eds) Modulation of Oxidative Stress in Heart Disease. Springer, Singapore. https://doi.org/10.1007/978-981-13-8946-7_24

Download citation

Publish with us

Policies and ethics

Search

Navigation