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Selenium exerts protective effects on inflammatory cardiovascular damage: molecular aspects via SIRT1/p53 and Cyt-c/Cas-3 pathways

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Abstract

Background

Systemic inflammatory response could affect many systems. Cardiac dysfunction develops due to cardiovascular system damage and could be mortal. Selenium is a trace element that can be used as a dietary supplement and has antioxidant, anti-inflammatory, and anti-apoptotic properties. This study aims to evaluate the protective effects of selenium on cardiovascular damage via silenced information regulator 1 (SIRT1)/p53 and cytochrome C (Cyt-c)/ caspase-3 (Cas-3) pathways.

Methods and results

Thirty-two rats were randomly divided into 4 groups as control, LPS (0.1 mg/kg, intraperitoneally(i.p.), 2–7 days) and LPS + Selenium (LPS-0.1 mg/kg, i.p., 2–7 days, selenium − 100 µg/kg, i.p., 1–7 days) and selenium (100 µg/kg, i.p., 1–7 days) group. On the 8th day of the experiment, rats were sacrificed. Blood samples and half of the left ventricles were collected for biochemical and genetic analysis. The remaining left ventricles and aorta were taken for histological and immunohistochemical analysis. In the LPS group myocardial hemorrhages, hyperemia, and endothelial cell loss were observed. Also, Cas-3 and vascular endothelial growth factor (VEGF) expressions; creatine kinase-MB (CK-MB), lactate dehydrogenase (LDH), tumor necrosis factor-alpha (TNF-α), ischemia modified albumin (IMA), total oxidant status (TOS), oxidative stress index (OSI) levels; p53, Cyt-c, Cas-3 mRNA expressions increased while total antioxidant status (TAS) levels, glutathione peroxidase (GPx) activity, SIRT1 mRNA expression decreased. Selenium treatment reversed all these changes.

Conclusion

Selenium showed protective effects on cardiovascular injury via regulating SIRT1/p53 and Cyt-c/Cas-3 pathways. This study enlightened the possible usage of selenium on cardiotoxicity.

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References

  1. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J et al (2018) Inflammatory responses and inflammation-associated diseases in organs. Oncotarget 9(6):7204–7218. https://doi.org/10.18632/oncotarget.23208

    Article  Google Scholar 

  2. Bertini P, Guarracino F (2021) Pathophysiology of cardiogenic shock. Curr Opin Crit care 27(4):409–415

    Article  Google Scholar 

  3. Patel N, Bajaj NS, Doshi R, Gupta A, Kalra R, Singh A et al (2019) Cardiovascular events and hospital deaths among patients with severe sepsis. Am J Cardiol 123(9):1406–1413

    Article  Google Scholar 

  4. Urschel K, Cicha I (2015) TNF-α in the cardiovascular system: from physiology to therapy. Int J Interf Cytokine Mediat Res 7:9–25

    CAS  Google Scholar 

  5. Mittal M, Siddiqui MR, Tran K, Reddy SP, Malik AB (2014) Reactive oxygen species in inflammation and tissue injury. Antioxid Redox Signal 20(7):1126–1167. https://doi.org/10.1089/ars.2012.5149

    Article  CAS  Google Scholar 

  6. Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74

    Article  CAS  Google Scholar 

  7. Senoner T, Dichtl W (2019) Oxidative stress in cardiovascular diseases: still a therapeutic target? Nutrients 11:20909

    Article  Google Scholar 

  8. Handy DE, Joseph J, Loscalzo J (2021) Selenium, a micronutrient that modulates cardiovascular health via redox enzymology. Nutrients 13(9):3238. https://doi.org/10.3390/nu13093238

    Article  CAS  Google Scholar 

  9. Shimada BK, Alfulaij N, Seale LA (2021) The impact of selenium deficiency on cardiovascular function. Int J Mol Sci 22(19):10713. https://doi.org/10.3390/ijms221910713

    Article  CAS  Google Scholar 

  10. Manzanares W, Biestro A, Galusso F, Torre MH, Mañay N, Pittini G et al (2009) Serum selenium and glutathione peroxidase-3 activity: biomarkers of systemic inflammation in the critically ill? Intensive Care Med 35(5):882–889. https://doi.org/10.1007/s00134-008-1356-5

    Article  CAS  Google Scholar 

  11. Luo Y, He X, Hu L, Zhao J, Su K, Lei Y et al (2022) The relationship between plasma selenium, antioxidant status, inflammatory responses and ischemic cardiomyopathy: a case-control study based on matched propensity scores. J Inflamm Res 15:5757–5765. https://doi.org/10.2147/jir.S383476

    Article  Google Scholar 

  12. Shengyu C, Yinhua L, Yuanhong L, Jinbo Z, Can F, Hao X et al (2022) Selenium alleviates heart remodeling through Sirt1/AKT/GSK-3β pathway. Int Immunopharmacol 111:109158. https://doi.org/10.1016/j.intimp.2022.109158

    Article  CAS  Google Scholar 

  13. Zhang J, Zhang S-d, Wang P, Guo N, Wang W, Yao L-p et al (2019) Pinolenic acid ameliorates oleic acid-induced lipogenesis and oxidative stress via AMPK/SIRT1 signaling pathway in HepG2 cells. Eur J Pharmacol 861:172618

    Article  CAS  Google Scholar 

  14. Ren Bc Z, Yf L, Ss C, Xj, Yang X, Cui X et al (2020) Curcumin alleviates oxidative stress and inhibits apoptosis in diabetic cardiomyopathy via Sirt1-Foxo1 and PI3K‐Akt signalling pathways. J Cell Mol Med 24(21):12355–12367

    Article  Google Scholar 

  15. Sin TK, Tam BT, Yung BY, Yip SP, Chan LW, Wong CS et al (2015) Resveratrol protects against doxorubicin-induced cardiotoxicity in aged hearts through the SIRT1‐USP7 axis. J Physiol 593(8):1887–1899

    Article  CAS  Google Scholar 

  16. Dincer Y, Himmetoglu S, Bozcali E, Vural VA, Akcay T (2010) Circulating p53 and cytochrome c levels in acute myocardial infarction patients. J Thromb thrombolysis 29(1):41–45

    Article  CAS  Google Scholar 

  17. Wu S-W, Su C-H, Ho Y-C, Huang-Liu R, Tseng C-C, Chiang Y-W et al (2021) Genotoxic effects of 1-nitropyrene in macrophages are mediated through a p53-dependent pathway involving cytochrome c release, caspase activation, and PARP-1 cleavage. Ecotoxicol Environ Saf 213:112062

    Article  CAS  Google Scholar 

  18. Aly HA, El-Beshbishy HA, Banjar ZM (2012) Mitochondrial dysfunction induced impairment of spermatogenesis in LPS-treated rats: modulatory role of lycopene. Eur J Pharmacol 677(1–3):31–38

    Article  CAS  Google Scholar 

  19. Zolali E, Hamishehkar H, Maleki-Dizaji N, Majidi Zolbanin N, Ghavimi H, Kouhsoltani M et al (2014) Selenium effect on oxidative stress factors in septic rats. Adv Pharm Bull 4(3):289–293. https://doi.org/10.5681/apb.2014.042

    Article  CAS  Google Scholar 

  20. Bar–Or D, Lau E, Winkler JV (2000) A novel assay for cobalt-albumin binding and its potential as a marker for myocardial ischemia—a preliminary report. J Emerg Med 19(4):311–315

    Article  Google Scholar 

  21. Paglia DE, Valentine WN (1967) Studies on the quantitative and qualitative characterization of erythrocyte glutathione peroxidase. J Lab Clin Med 70(1):158–169

    CAS  Google Scholar 

  22. Erel O (2004) A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin Biochem 37(4):277–285

    Article  CAS  Google Scholar 

  23. Erel O (2005) A new automated colorimetric method for measuring total oxidant status. Clin Biochem 38(12):1103–1111

    Article  CAS  Google Scholar 

  24. Altindag O, Erel O, Soran N, Celik H, Selek S (2008) Total oxidative/anti-oxidative status and relation to bone mineral density in osteoporosis. Rheumatol Int 28(4):317–321

    Article  CAS  Google Scholar 

  25. Shapouri-Moghaddam A, Mohammadian S, Vazini H, Taghadosi M, Esmaeili SA, Mardani F et al (2018) Macrophage plasticity, polarization, and function in health and disease. J Cell Physiol 233(9):6425–6440. https://doi.org/10.1002/jcp.26429

    Article  CAS  Google Scholar 

  26. Asci H, Ozmen O, Erzurumlu Y, Savas H, Temel EN, Icten P et al (2021) Ameliorative effects of pregabalin on LPS induced endothelial and cardiac toxicity. Biotech Histochem 96(5):364–375

    Article  CAS  Google Scholar 

  27. Araujo-Jorge TC, Rivera MT, Vanderpas J, Garzoni LR, Carvalho ACC, Waghabi MC et al (2022) Selenium, TGF-beta and infectious endemic cardiopathy: lessons from Benchwork to clinical application in Chagas disease. Biomolecules 12(3):349. https://doi.org/10.3390/biom12030349

    Article  CAS  Google Scholar 

  28. Zhou X, Wang Z, Chen J, Wang W, Song D, Li S et al (2014) Increased levels of IL-6, IL-1β, and TNF-α in Kashin–Beck disease and rats induced by T-2 toxin and selenium deficiency. Rheumatol Int 34(7):995–1004

    Article  CAS  Google Scholar 

  29. Yang HL, Huang PJ, Liu YR, Kumar KJ, Hsu LS, Lu TL et al (2014) Toona sinensis inhibits LPS-induced inflammation and migration in vascular smooth muscle cells via suppression of reactive oxygen species and NF-κB signaling pathway. Oxid Med Cell Longev. 2014. https://doi.org/10.1155/2014/901315

    Article  Google Scholar 

  30. L’Heureux M, Sternberg M, Brath L, Turlington J, Kashiouris MG (2020) Sepsis-induced cardiomyopathy: a comprehensive review. Curr Cardiol Rep 22(5):35. https://doi.org/10.1007/s11886-020-01277-2

    Article  Google Scholar 

  31. Zilinyi R, Czompa A, Czegledi A, Gajtko A, Pituk D, Lekli I et al (2018) The cardioprotective effect of metformin in doxorubicin-induced cardiotoxicity: the role of autophagy. Molecules 23(5):1184

    Article  Google Scholar 

  32. Gunes S, Sahinturk V, Karasati P, Sahin IK, Ayhanci A (2017) Cardioprotective effect of selenium against cyclophosphamide-induced cardiotoxicity in rats. Biol Trace Elem Res 177(1):107–114

    Article  CAS  Google Scholar 

  33. Dallak M (2017) A synergistic protective effect of selenium and taurine against experimentally induced myocardial infarction in rats. Arch Physiol Biochem 123(5):344–355

    Article  CAS  Google Scholar 

  34. Shirazi LF, Bissett J, Romeo F, Mehta JL (2017) Role of inflammation in heart failure. Curr Atheroscler Rep 19(6):1–9

    Article  CAS  Google Scholar 

  35. Schoots MH, Gordijn SJ, Scherjon SA, van Goor H, Hillebrands J-L (2018) Oxidative stress in placental pathology. Placenta 69:153–161

    Article  CAS  Google Scholar 

  36. Maulik N, Yoshida T, Das DK (1999) Regulation of cardiomyocyte apoptosis in ischemic reperfused mouse heart by glutathione peroxidase. Mol Cell Biochem 196(1–2):13–21. https://doi.org/10.1007/978-1-4615-5097-6_2

    Article  CAS  Google Scholar 

  37. Xiong Y, Liu X, Lee CP, Chua BH, Ho YS (2006) Attenuation of doxorubicin-induced contractile and mitochondrial dysfunction in mouse heart by cellular glutathione peroxidase. Free Radic Biol Med 41(1):46–55. https://doi.org/10.1016/j.freeradbiomed.2006.02.024

    Article  CAS  Google Scholar 

  38. Feng Y, Madungwe NB, Imam Aliagan AD, Tombo N, Bopassa JC (2019) Liproxstatin-1 protects the mouse myocardium against ischemia/reperfusion injury by decreasing VDAC1 levels and restoring GPX4 levels. Biochem Biophys Res Commun 520(3):606–611. https://doi.org/10.1016/j.bbrc.2019.10.006

    Article  CAS  Google Scholar 

  39. Geng H, Chen L, Su Y, Xu Q, Fan M, Huang R et al (2022) Mir-431-5p regulates apoptosis of cardiomyocytes after acute myocardial infarction via targeting selenoprotein T. Physiol Res 71(1):55–62. https://doi.org/10.33549/physiolres.934683

    Article  CAS  Google Scholar 

  40. Rocca C, Boukhzar L, Granieri MC, Alsharif I, Mazza R, Lefranc B et al (2018) A selenoprotein T-derived peptide protects the heart against ischaemia/reperfusion injury through inhibition of apoptosis and oxidative stress. Acta Physiol (Oxf) 223(4):e13067. https://doi.org/10.1111/apha.13067

    Article  CAS  Google Scholar 

  41. Brown DA, Perry JB, Allen ME, Sabbah HN, Stauffer BL, Shaikh SR et al (2017) Mitochondrial function as a therapeutic target in heart failure. Nat Rev Cardiol 14(4):238–250

    Article  CAS  Google Scholar 

  42. Peoples JN, Saraf A, Ghazal N, Pham TT, Kwong JQ (2019) Mitochondrial dysfunction and oxidative stress in heart disease. Exp Mol Med 51(12):1–13

    Article  CAS  Google Scholar 

  43. Kura B, Szeiffova Bacova B, Kalocayova B, Sykora M, Slezak J (2020) Oxidative stress-responsive microRNAs in heart injury. Int J Mol Sci 21(1):358

    Article  CAS  Google Scholar 

  44. Park S-A, Joo N-R, Park J-H, Oh S-M (2021) Role of the SIRT1/p53 regulatory axis in oxidative stress–mediated granulosa cell apoptosis. Mol Med Rep 23(1):1

    Article  Google Scholar 

  45. Aykutoglu G, Tartik M, Darendelioglu E, Ayna A, Baydas G (2020) Melatonin and vitamin E alleviate homocysteine-induced oxidative injury and apoptosis in endothelial cells. Mol Biol Rep 47(7):5285–5293

    Article  CAS  Google Scholar 

  46. Guo T, Jiang Z-B, Tong Z-Y, Zhou Y, Chai X-P, Xiao X-Z (2020) Shikonin ameliorates LPS-induced cardiac dysfunction by SIRT1-dependent inhibition of NLRP3 inflammasome. Front Physiol 11:570441

    Article  Google Scholar 

  47. An R, Zhao L, Xu J, Xi C, Li H, Shen G et al (2016) Resveratrol alleviates sepsis–induced myocardial injury in rats by suppressing neutrophil accumulation, the induction of TNF–α and myocardial apoptosis via activation of Sirt1. Mol Med Rep 14(6):5297–5303

    Article  CAS  Google Scholar 

  48. Kumar GS, Kulkarni A, Khurana A, Kaur J, Tikoo K (2014) Selenium nanoparticles involve HSP-70 and SIRT1 in preventing the progression of type 1 diabetic nephropathy. Chemico-Biol Interact 223:125–133

    Article  CAS  Google Scholar 

  49. Pant R, Sharma N, Kabeer SW, Sharma S, Tikoo K (2022) Selenium-enriched probiotic alleviates western diet-induced non-alcoholic fatty liver disease in rats via modulation of autophagy through AMPK/SIRT-1 pathway. Biol Trace Elem Res 1–14

  50. Khazdouz M, Daryani NE, Alborzi F, Jazayeri MH, Farsi F, Hasani M et al (2020) Effect of selenium supplementation on expression of SIRT1 and PGC-1α genes in ulcerative colitis patients: a double blind randomized clinical trial. Clin Nutr Res 9(4):284

    Article  Google Scholar 

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Funding

The authors declare that no funds, grants, or other support were received during this study.

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Authors and Affiliations

  1. Faculty of Medicine, Department of Biochemistry, Suleyman Demirel University, 32300, Isparta, Turkey

    Ilter Ilhan

  2. Faculty of Medicine, Department of Pharmacology, Suleyman Demirel University, Isparta, Turkey

    Halil Asci, Orhan Berk Imeci & Mehmet Abdulkadir Sevuk

  3. Faculty of Medicine, Department of Medical Genetic, Suleyman Demirel University, Isparta, Turkey

    Muhammet Yusuf Tepebasi

  4. Faculty of Medicine, Department of Infectious Disease, Suleyman Demirel University, Isparta, Turkey

    Esra Nurlu Temel

  5. Faculty of Veterinary, Department of Pathology, Burdur Mehmet Akif Ersoy University, Burdur, Turkey

    Ozlem Ozmen

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  1. Ilter Ilhan
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  3. Muhammet Yusuf Tepebasi
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  4. Orhan Berk Imeci
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Contributions

All of the authors contributed to the design of the study, the collection of samples, the analysis, and the interpretation of data.

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Correspondence to Ilter Ilhan.

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Conflict of interest

 Dr. Ilter ILHAN and the co-authors have no conflicts of interest to declare in association with this study.

Ethical approval

The animal experiments were approved by the local animal ethics committee of Suleyman Demirel University (Ethic No: 17.02.2022/02–24). The experiment was conducted according to the recommendations for animal care and experimentation of the relevant European Communities Council Directive (86/609/EEC).

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Ilhan, I., Asci, H., Tepebasi, M.Y. et al. Selenium exerts protective effects on inflammatory cardiovascular damage: molecular aspects via SIRT1/p53 and Cyt-c/Cas-3 pathways. Mol Biol Rep 50, 1627–1637 (2023). https://doi.org/10.1007/s11033-022-08192-5

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