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Melatonin Alleviates Ovariectomy-Induced Cardiovascular Inflammation in Sedentary or Exercised Rats by Upregulating SIRT1

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Abstract

We aimed to evaluate the impact of hormone replacement, melatonin, or exercise alone or their combination on oxidative damage and functional status of heart, brain, and aorta of ovariectomized (OVX) rats and to determine whether the signaling pathway is dependent on sirtuin-1 (SIRT1). Ovariectomized Sprague Dawley rats were orally given either a hormone replacement therapy (1 mg/kg/day,17β estradiol; HRT) or melatonin (4 mg/kg/day) or HRT + melatonin treatments or tap water, while each group was further divided into sedentary and exercise (30 min/5 days/week) groups. After the heart rate measurements and memory tests were performed, trunk blood was collected at the end of the 10th week to determine metabolic parameters in serum samples. Tissue samples of abdominal aorta, heart, and brain were taken for biochemical measurements and histopathological evaluation. Heart rates and memory performances of the OVX rats were not changed significantly by none of the applications. Melatonin treatment or its co-administration with HRT upregulated the expressions of IL-10 and SIRT1, reduced the expressions of IL-6 and TNF-α, and reduced DNA damage in the hearts and thoracic aortae of non-exercised rats. Co-administration of melatonin and HRT to exercised OVX rats reduced inflammatory response and upregulated SIRT1 expression in the aortic and cardiac tissues. The present study suggests that melatonin treatment, either alone or in combination with exercise and/or HRT, upregulates SIRT1 expression and alleviates oxidative injury and inflammation in the hearts and aortas of OVX rats. Melatonin should be considered in alleviating cardiovascular disease risk in postmenopausal women.

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References

  1. IfH, Metrics.  2019. Evaluation: Global Burden of Disease Collaborative Network. Global Burden of Disease Study 2019 (GBD 2019 Results. Institute for health metrics and evaluation Seattle.

  2. Vogel, B., M. Acevedo, Y. Appelman, C.N.B. Merz, A. Chieffo, G.A. Figtree, M. Guerrero, V. Kunadian, C.S. Lam and A.H. Maas. 2021. The Lancet women and cardiovascular disease Commission: reducing the global burden by 2030. The Lancet.

  3. Abubakar, I., T. Tillmann, and A. Banerjee. 2015. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: A systematic analysis for the Global Burden of Disease Study 2013. Lancet 385: 117–171.

    Article  Google Scholar 

  4. Roth, G.A., G.A. Mensah, C.O. Johnson, G. Addolorato, E. Ammirati, L.M. Baddour, N.C. Barengo, A.Z. Beaton, E.J. Benjamin, and C.P. Benziger. 2020. Global burden of cardiovascular diseases and risk factors, 1990–2019: Update from the GBD 2019 study. Journal of the American College of Cardiology 76: 2982–3021.

    Article  PubMed  PubMed Central  Google Scholar 

  5. https://www.who.int/news-room/fact-sheets/detail/cardiovascular-diseases-(cvds)

  6. Yusuf, S., S. Hawken, S. Ôunpuu, T. Dans, A. Avezum, F. Lanas, M. McQueen, A. Budaj, P. Pais, and J. Varigos. 2004. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): Case-control study. The lancet 364: 937–952.

    Article  Google Scholar 

  7. Honigberg, M.C., S.M. Zekavat, K. Aragam, P. Finneran, D. Klarin, D.L. Bhatt, J.L. Januzzi, N.S. Scott, and P. Natarajan. 2019. Association of premature natural and surgical menopause with incident cardiovascular disease. JAMA 322: 2411–2421.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Mendelsohn, M.E., and R.H. Karas. 2005. Molecular and cellular basis of cardiovascular gender differences. Science 308: 1583–1587.

    Article  CAS  PubMed  Google Scholar 

  9. Moreau, K.L., K.L. Hildreth, J. Klawitter, P. Blatchford, and W.M. Kohrt. 2020. Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress. GeroScience 42: 1699–1714.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sack, M.N., D. Rader, and R.O. Cannon. 1994. Oestrogen and inhibition of oxidation of low-density lipoproteins in postmenopausal women. The Lancet 343: 269–270.

    Article  CAS  Google Scholar 

  11. Rosano, G., C. Vitale, G. Marazzi, and M. Volterrani. 2007. Menopause and cardiovascular disease: The evidence. Climacteric 10: 19–24.

    Article  CAS  PubMed  Google Scholar 

  12. Zhao, D., E. Guallar, P. Ouyang, V. Subramanya, D. Vaidya, C.E. Ndumele, J.A. Lima, M.A. Allison, S.J. Shah, and A.G. Bertoni. 2018. Endogenous sex hormones and incident cardiovascular disease in post-menopausal women. Journal of the American College of Cardiology 71: 2555–2566.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Manson, J.E., R.T. Chlebowski, M.L. Stefanick, A.K. Aragaki, J.E. Rossouw, R.L. Prentice, G. Anderson, B.V. Howard, C.A. Thomson, and A.Z. LaCroix. 2013. Menopausal hormone therapy and health outcomes during the intervention and extended poststopping phases of the Women’s Health Initiative randomized trials. JAMA 310: 1353–1368.

    Article  CAS  PubMed  Google Scholar 

  14. Lundberg, G. and N. Wenger. 2019. Menopause hormone therapy: what a cardiologist needs to know. American college of cardiology 1.

  15. Stojanovska, L., V. Apostolopoulos, R. Polman, and E. Borkoles. 2014. To exercise, or, not to exercise, during menopause and beyond. Maturitas 77: 318–323.

    Article  PubMed  Google Scholar 

  16. Lin, Y.-Y., and S.-D. Lee. 2018. Cardiovascular benefits of exercise training in postmenopausal hypertension. International journal of molecular sciences 19: 2523.

    Article  PubMed Central  Google Scholar 

  17. Dodda, B.R., C.D. Bondi, M. Hasan, W.P. Clafshenkel, K.M. Gallagher, M.P. Kotlarczyk, S. Sethi, E. Buszko, J.J. Latimer, and J.M. Cline. 2019. Co-administering melatonin with an estradiol-progesterone menopausal hormone therapy represses mammary cancer development in a mouse model of HER2-positive breast cancer. Frontiers in oncology 9: 525.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Gürler, E.B., Ö.T. Çilingir-Kaya, I. Peker Eyüboglu, F. Ercan, M. Akkiprik, R.J. Reiter, and B.Ç. Yegen. 2019. Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats. Cell biochemistry and function 37: 102–112.

    Article  PubMed  Google Scholar 

  19. Yi, M., S. Wang, T. Wu, X. Zhang, L. Jiang, and X. Fang. 2021. Effects of exogenous melatonin on sleep quality and menopausal symptoms in menopausal women: A systematic review and meta-analysis of randomized controlled trials. Menopause 28: 717–725.

    Article  PubMed  Google Scholar 

  20. Allegra, M., R.J. Reiter, D.X. Tan, C. Gentile, L. Tesoriere, and M. Livrea. 2003. The chemistry of melatonin’s interaction with reactive species. Journal of pineal research 34: 1–10.

    Article  CAS  PubMed  Google Scholar 

  21. Arabacı Tamer, S., A. Yildirim, Ö. Çevik, B. Aksu, M. Yüksel, E. Dertsiz, S. Şirvancı and B.Ç. Yegen. 2021. The ameliorative effects of melatonin on acetic acid-induced gastric ulcer in rats via its modulatory effects on gut microbiota.

  22. Poeggeler, B., S. Thuermann, A. Dose, M. Schoenke, S. Burkhardt, and R. Hardeland. 2002. Melatonin’s unique radical scavenging properties–roles of its functional substituents as revealed by a comparison with its structural analogs. Journal of pineal research 33: 20–30.

    Article  CAS  PubMed  Google Scholar 

  23. Şener, G., H. Toklu, C. Kapucu, F. Ercan, G. Erkanlı, A. Kaçmaz, M. Tilki, and B.Ç. Yeğen. 2005. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surgery today 35: 52–59.

    Article  PubMed  Google Scholar 

  24. Tan, D.X., L.C. Manchester, R. Hardeland, S. Lopez-Burillo, J.C. Mayo, R.M. Sainz, and R.J. Reiter. 2003. Melatonin: A hormone, a tissue factor, an autocoid, a paracoid, and an antioxidant vitamin. Journal of pineal research 34: 75–78.

    Article  CAS  PubMed  Google Scholar 

  25. Yildirim, A., S.A. Tamer, D. Sahin, F. Bagriacik, M.M. Kahraman, N.D. Onur, Y.B. Cayirli, Ö.T.C. Kaya, B. Aksu, and E. Akdeniz. 2019. The effects of antibiotics and melatonin on hepato-intestinal inflammation and gut microbial dysbiosis induced by a short-term high-fat diet consumption in rats. British Journal of Nutrition 122: 841–855.

    Article  CAS  PubMed  Google Scholar 

  26. Bubenik, G., and S. Konturek. 2011. Melatonin and aging: Prospects for human treatment. Journal of physiology and pharmacology 62: 13.

    CAS  PubMed  Google Scholar 

  27. Hardeland, R. 2012. Melatonin in aging and disease—multiple consequences of reduced secretion, options and limits of treatment. Aging and disease 3: 194.

    PubMed  Google Scholar 

  28. Hardeland, R. 2019. Aging, melatonin, and the pro-and anti-inflammatory networks. International journal of molecular sciences 20: 1223.

    Article  CAS  PubMed Central  Google Scholar 

  29. Kireev, R., A. Tresguerres, C. Garcia, C. Ariznavarreta, E. Vara, and J.A. Tresguerres. 2008. Melatonin is able to prevent the liver of old castrated female rats from oxidative and pro-inflammatory damage. Journal of pineal research 45: 394–402.

    Article  CAS  PubMed  Google Scholar 

  30. Baxi, D., P. Singh, K. Vachhrajani, and A. Ramachandran. 2012. Melatonin supplementation therapy as a potent alternative to ERT in ovariectomized rats. Climacteric 15: 382–392.

    Article  CAS  PubMed  Google Scholar 

  31. Chen, Z., C.C. Chua, J. Gao, R.C. Hamdy, and B.H. Chua. 2003. Protective effect of melatonin on myocardial infarction. American Journal of Physiology-Heart and Circulatory Physiology 284: H1618–H1624.

    Article  CAS  PubMed  Google Scholar 

  32. Geary, G.G., D.N. Krause, and S. Duckles. 1997. Melatonin directly constricts rat cerebral arteries through modulation of potassium channels. American Journal of Physiology-Heart and Circulatory Physiology 273: H1530–H1536.

    Article  CAS  Google Scholar 

  33. Lee, Y.M., H.R. Chen, G. Hsiao, J.R. Sheu, J.J. Wang, and M.H. Yen. 2002. Protective effects of melatonin on myocardial ischemia/reperfusion injury in vivo. Journal of pineal research 33: 72–80.

    Article  CAS  PubMed  Google Scholar 

  34. Pei, Z., S.F. Pang, and R.T.F. Cheung. 2003. Administration of melatonin after onset of ischemia reduces the volume of cerebral infarction in a rat middle cerebral artery occlusion stroke model. Stroke 34: 770–775.

    Article  CAS  PubMed  Google Scholar 

  35. Sahna, E., H. Parlakpinar, Y. Turkoz, and A. Acet. 2005. Protective effects of melatonin on myocardial ischemia-reperfusion induced infarct size and oxidative changes. Physiological research 54: 491.

    Article  CAS  PubMed  Google Scholar 

  36. Sadeghi, M., S. Khosrawi, K. Heshmat-Ghahdarijani, Y. Gheisari, H. Roohafza, M. Mansoorian, and S.G. Hoseini. 2020. Effect of melatonin on heart failure: Design for a double-blinded randomized clinical trial. ESC Heart Failure 7: 3142–3150.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Treister‐Goltzman, Y. and R. Peleg. 2021. Melatonin and the health of menopausal women: a systematic review. Journal of pineal research e12743.

  38. Kitada, M., Y. Ogura, and D. Koya. 2016. The protective role of Sirt1 in vascular tissue: Its relationship to vascular aging and atherosclerosis. Aging (Albany NY) 8: 2290.

    Article  CAS  Google Scholar 

  39. Babayev, H., S. Arabaci-Tamer, A. Yildirim, D. Kayali, F. Ercan, C. Yegen, M.U. Ugurlu, and B.Ç. Yeğen. 2021. Sleeve gastrectomy–induced endocrine changes in the remnant stomachs of premenopausal and postmenopausal rats: Role of the estrogen receptors. Surgery for Obesity and Related Diseases 17: 193–207.

    Article  PubMed  Google Scholar 

  40. Koyuncuoğlu, T., S. Arabacı Tamer, C. Erzik, A. Karagöz, D. Akakın, M. Yüksel, and B.Ç. Yeğen. 2019. Oestrogen receptor ERα and ERβ agonists ameliorate oxidative brain injury and improve memory dysfunction in rats with an epileptic seizure. Experimental physiology 104: 1911–1928.

    Article  PubMed  Google Scholar 

  41. Arabacı Tamer, S., S. Üçem, B. Büke, M. Güner, A.G. Karaküçük, N. Yiğit, S. Şirvancı, Ö. Çevik, F. Ercan, and B.Ç. Yeğen. 2020. Regular moderate exercise alleviates gastric oxidative damage in rats via the contribution of oxytocin receptors. The Journal of physiology 598: 2355–2370.

    Article  PubMed  Google Scholar 

  42. Radák, Z., T. Kaneko, S. Tahara, H. Nakamoto, J. Pucsok, M. Sasvári, C. Nyakas, and S. Goto. 2001. Regular exercise improves cognitive function and decreases oxidative damage in rat brain. Neurochemistry international 38: 17–23.

    Article  PubMed  Google Scholar 

  43. Bevins, R.A., and J. Besheer. 2006. Object recognition in rats and mice: A one-trial non-matching-to-sample learning task to study’recognition memory’. Nature protocols 1: 1306–1311.

    Article  PubMed  Google Scholar 

  44. Elrod, K., and J.J. Buccafusco. 1988. An evaluation of the mechanism of scopolamine-induced impairment in two passive avoidance protocols. Pharmacology Biochemistry and Behavior 29: 15–21.

    Article  CAS  PubMed  Google Scholar 

  45. Bradley, P.P., D.A. Priebat, R.D. Christensen, and G. Rothstein. 1982. Measurement of cutaneous inflammation: Estimation of neutrophil content with an enzyme marker. Journal of Investigative Dermatology 78: 206–209.

    Article  CAS  PubMed  Google Scholar 

  46. Tuğtepe, H., G. Şener, N.K. Bıyıklı, M. Yüksel, Ş Çetinel, N. Gedik, and B.Ç. Yeğen. 2007. The protective effect of oxytocin on renal ischemia/reperfusion injury in rats. Regulatory peptides 140: 101–108.

    Article  PubMed  Google Scholar 

  47. Machi, J.F., D. da Silva Dias, S.C. Freitas, O.A. de Moraes, M.B. da Silva, P.L. Cruz, C. Mostarda, V.M. Salemi, M. Morris, and K. De Angelis. 2016. Impact of aging on cardiac function in a female rat model of menopause: Role of autonomic control, inflammation, and oxidative stress. Clinical Interventions in Aging 11: 341.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Hogarth, A.J., L.N. Graham, J.H. Corrigan, J. Deuchars, D.A. Mary, and J.P. Greenwood. 2011. Sympathetic nerve hyperactivity and its effect in postmenopausal women. Journal of hypertension 29: 2167–2175.

    Article  CAS  PubMed  Google Scholar 

  49. Pradham, A., J. Manson, J. Rossouw, D. Siscovick, C. Mouton, N. Rifai, R. Wallace, R. Jackson, M. Pettinger, and P. Ridker. 2002. Inflammatory biomarkers, hormone replacement therapy, and incident coronary heart disease. JAMA 288: 980–987.

    Article  Google Scholar 

  50. Ybañez-Julca, R.O., D. Asunción-Alvarez, J. Palacios, and C.R. Nwokocha. 2021. Maca extracts and estrogen replacement therapy in ovariectomized rats exposed at high altitude. Reproductive Medicine and Biology 20: 88–95.

    Article  PubMed  Google Scholar 

  51. Esmailidehaj, M., F. Kuchakzade, M.E. Rezvani, Z. Farhadi, H. Esmaeili, and H. Azizian. 2020. 17β-Estradiol improves insulin signalling and insulin resistance in the aged female hearts: Role of inflammatory and anti-inflammatory cytokines. Life sciences 253: 117673.

    Article  CAS  PubMed  Google Scholar 

  52. Hodgin, J.B., J.H. Krege, R.L. Reddick, K.S. Korach, O. Smithies, and N. Maeda. 2001. Estrogen receptor α is a major mediator of 17β-estradiol’s atheroprotective effects on lesion size in Apoe–/–mice. The Journal of clinical investigation 107: 333–340.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Hodgin, J.B., and N. Maeda. 2002. Minireview: Estrogen and mouse models of atherosclerosis. Endocrinology 143: 4495–4501.

    Article  CAS  PubMed  Google Scholar 

  54. Persky, A.M., P.S. Greene, L. Stubley, C.O. Howell, L. Zaulyanov, G.A. Brazeau, and J.W. Simpkins. 2000. Protective effect of estrogens against oxidative damage to heart and skeletal muscle in vivo and in vitro (44463). Proceedings of the Society for Experimental Biology and Medicine 223: 59–66.

    Article  CAS  PubMed  Google Scholar 

  55. Zhu, X., Z. Tang, B. Cong, J. Du, C. Wang, L. Wang, X. Ni, and J. Lu. 2013. Estrogens increase cystathionine-γ-lyase expression and decrease inflammation and oxidative stress in the myocardium of ovariectomized rats. Menopause 20: 1084–1091.

    Article  PubMed  Google Scholar 

  56. Hodis, H.N., W.J. Mack, V.W. Henderson, D. Shoupe, M.J. Budoff, J. Hwang-Levine, Y. Li, M. Feng, L. Dustin, and N. Kono. 2016. Vascular effects of early versus late postmenopausal treatment with estradiol. New England Journal of Medicine 374: 1221–1231.

    Article  CAS  PubMed  Google Scholar 

  57. Salpeter, S.R., J.M. Walsh, E. Greyber, and E.E. Salpeter. 2006. Brief report: Coronary heart disease events associated with hormone therapy in younger and older women. Journal of general internal medicine 21: 363–366.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Schierbeck, L.L., L. Rejnmark, C.L. Tofteng, L. Stilgren, P. Eiken, L. Mosekilde, L. Køber and J.-E.B. Jensen. 2012. Effect of hormone replacement therapy on cardiovascular events in recently postmenopausal women: randomised trial. Bmj 345.

  59. van Baal, M.W., P. Kenemans, M.J. van der Mooren, H. Kessel, J.J. Emeis, and C.D. Stehouwer. 1999. Increased C-reactive protein levels during short-term hormone replacement therapy in healthy postmenopausal women. Thrombosis and haemostasis 81: 925–928.

    Article  PubMed  Google Scholar 

  60. de Oliveira, S.G., E.R.G. Claudio, S.A. de Almeida, V. Mengal, F.B. da Silva, N.F. Silva, H. Mauad, and G.R. de Abreu. 2019. Exercise training improves vascular reactivity in ovariectomized rats subjected to myocardial infarction. PLoS ONE 14: e0215568.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Shimojo, G.L., and D.D. Silva Dias, C. Malfitano, I.C. Sanches, S. Llesuy, L. Ulloa, M.-C. Irigoyen and K. De Angelis. 2018. Combined aerobic and resistance exercise training improve hypertension associated with menopause. Frontiers in physiology 9: 1471.

    Article  PubMed  PubMed Central  Google Scholar 

  62. Szabó, R., D. Börzsei, Z. Karácsonyi, R. Gesztelyi, K. Nemes, A.M. Berkó, M. Veszelka, S. Török, K. Kupai, and C. Varga. 2019. Postconditioning-like effect of exercis: New paradigm in experimental menopause. American Journal of Physiology-Heart and Circulatory Physiology 316: H400–H407.

    Article  PubMed  Google Scholar 

  63. Tang, Z., Y. Wang, X. Zhu, X. Ni, and J. Lu. 2016. Exercise increases cystathionine-γ-lyase expression and decreases the status of oxidative stress in myocardium of ovariectomized rats. International Heart Journal 57: 96–103.

    Article  CAS  PubMed  Google Scholar 

  64. Varga, C., M. Veszelka, K. Kupai, D. Börzsei, Z. Deim, R. Szabó, S. Török, D. Priksz, R. Gesztelyi, and B. Juhász. 2018. The effects of exercise training and high triglyceride diet in an estrogen depleted rat model: The role of the heme oxygenase system and inflammatory processes in cardiovascular risk. Journal of sports science & medicine 17: 580.

    Google Scholar 

  65. Grindler, N.M., and N.F. Santoro. 2015. Menopause and exercise. Menopause 22: 1351–1358.

    Article  PubMed  Google Scholar 

  66. Wegge, J.K., C.K. Roberts, T.H. Ngo, and R.J. Barnard. 2004. Effect of diet and exercise intervention on inflammatory and adhesion molecules in postmenopausal women on hormone replacement therapy and at risk for coronary artery disease. Metabolism 53: 377–381.

    Article  CAS  PubMed  Google Scholar 

  67. Al-Nakkash, L., T. Janjulia, K. Peterson, D. Lucy, D. Wilson, A. Peterson, W. Prozialeck, and T. Broderick. 2014. Genistein and exercise do not improve cardiovascular risk factors in the ovariectomized rat. Climacteric 17: 136–147.

    Article  CAS  PubMed  Google Scholar 

  68. Almeida, S.A.d., E.R. Claudio, V. Mengal, G.A. Brasil, E. Merlo, P.L. Podratz, J.B. Graceli, S.A. Gouvea and G.R.d. Abreu. 2018. Estrogen therapy worsens cardiac function and remodeling and reverses the effects of exercise training after myocardial infarction in ovariectomized female rats. Frontiers in physiology 9: 1242.

    Article  Google Scholar 

  69. Phungphong, S., A. Kijtawornrat, J. Wattanapermpool, and T. Bupha-Intr. 2016. Regular exercise modulates cardiac mast cell activation in ovariectomized rats. The Journal of Physiological Sciences 66: 165–173.

    Article  CAS  PubMed  Google Scholar 

  70. Bulut, E.C., L. Abueid, F. Ercan, S. Süleymanoğlu, M. Ağırbaşlı, and B.Ç. Yeğen. 2016. Treatment with oestrogen-receptor agonists or oxytocin in conjunction with exercise protects against myocardial infarction in ovariectomized rats. Experimental physiology 101: 612–627.

    Article  CAS  PubMed  Google Scholar 

  71. Cancer, C.G.o.H.F.i.B. 2019. Type and timing of menopausal hormone therapy and breast cancer risk: Individual participant meta-analysis of the worldwide epidemiological evidence. The Lancet 394: 1159–1168.

    Article  Google Scholar 

  72. Lee, J.-Y., and D.-C. Lee. 2014. Urine 6-sulfatoxymelatonin levels are inversely associated with arterial stiffness in post-menopausal women. Maturitas 78: 117–122.

    Article  CAS  PubMed  Google Scholar 

  73. Shafiei, E., M. Bahtoei, P. Raj, A. Ostovar, D. Iranpour, S. Akbarzadeh, H. Shahryari, A. Anvaripour, R. Tahmasebi, T. Netticadan, and A. Movahed. 2018. Effects of N-acetyl cysteine and melatonin on early reperfusion injury in patients undergoing coronary artery bypass grafting: A randomized, open-labeled, placebo-controlled trial. Medicine (Baltimore) 97: e11383.

    Article  CAS  Google Scholar 

  74. Tamura, H., Y. Nakamura, A. Narimatsu, Y. Yamagata, A. Takasaki, R.J. Reiter, and N. Sugino. 2008. Melatonin treatment in peri- and postmenopausal women elevates serum high-density lipoprotein cholesterol levels without influencing total cholesterol levels. Journal of Pineal Research 45: 101–105.

    Article  CAS  PubMed  Google Scholar 

  75. Baxi, D.B., P.K. Singh, K.D. Vachhrajani, and A.V. Ramachandran. 2013. Melatonin supplementation in rat ameliorates ovariectomy-induced oxidative stress. Climacteric 16: 274–283.

    Article  CAS  PubMed  Google Scholar 

  76. Turgut, O., A.A. Ay, H. Turgut, A. Ay, S. Kafkas, and T. Dost. 2013. Effects of melatonin and dexpanthenol on antioxidant parameters when combined with estrogen treatment in ovariectomized rats. Age (Dordrecht, Netherlands) 35: 2229–2235.

    Article  CAS  Google Scholar 

  77. Tengattini, S., R.J. Reiter, D.X. Tan, M.P. Terron, L.F. Rodella, and R. Rezzani. 2008. Cardiovascular diseases: Protective effects of melatonin. Journal of pineal research 44: 16–25.

    CAS  PubMed  Google Scholar 

  78. Broussy, S., H. Laaroussi, and M. Vidal. 2020. Biochemical mechanism and biological effects of the inhibition of silent information regulator 1 (SIRT1) by EX-527 (SEN0014196 or selisistat). Journal of enzyme inhibition and medicinal chemistry 35: 1124–1136.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Hsu, C.-P., P. Zhai, T. Yamamoto, Y. Maejima, S. Matsushima, N. Hariharan, D. Shao, H. Takagi, S. Oka, and J. Sadoshima. 2010. Silent information regulator 1 protects the heart from ischemia/reperfusion. Circulation 122: 2170–2182.

    Article  PubMed  PubMed Central  Google Scholar 

  80. Singh, V. and S. Ubaid. 2020. Role of silent information regulator 1 (SIRT1) in regulating oxidative stress and inflammation. Inflammation 43.

  81. Yang, Y., W. Duan, Y. Li, Z. Jin, J. Yan, S. Yu, and D. Yi. 2013. Novel role of silent information regulator 1 in myocardial ischemia. Circulation 128: 2232–2240.

    Article  PubMed  Google Scholar 

  82. Han, D., W. Huang, X. Li, L. Gao, T. Su, X. Li, S. Ma, T. Liu, C. Li, and J. Chen. 2016. Melatonin facilitates adipose-derived mesenchymal stem cells to repair the murine infarcted heart via the SIRT1 signaling pathway. Journal of pineal research 60: 178–192.

    Article  CAS  PubMed  Google Scholar 

  83. Hardeland, R. 2018. Melatonin and inflammation—story of a double-edged blade. Journal of pineal research 65: e12525.

    Article  PubMed  Google Scholar 

  84. Savran, M., H. Asci, O. Ozmen, Y. Erzurumlu, H. Savas, Y. Sonmez, and Y. Sahin. 2019. Melatonin protects the heart and endothelium against high fructose corn syrup consumption–induced cardiovascular toxicity via SIRT-1 signaling. Human & experimental toxicology 38: 1212–1223.

    Article  CAS  Google Scholar 

  85. Zhao, L., R. An, Y. Yang, X. Yang, H. Liu, L. Yue, X. Li, Y. Lin, R.J. Reiter, and Y. Qu. 2015. Melatonin alleviates brain injury in mice subjected to cecal ligation and puncture via attenuating inflammation, apoptosis, and oxidative stress: The role of SIRT 1 signaling. Journal of pineal research 59: 230–239.

    Article  CAS  PubMed  Google Scholar 

  86. Chen, W., X. Chen, A.C. Chen, Q. Shi, G. Pan, M. Pei, H. Yang, T. Liu, and F. He. 2020. Melatonin restores the osteoporosis-impaired osteogenic potential of bone marrow mesenchymal stem cells by preserving SIRT1-mediated intracellular antioxidant properties. Free Radical Biology and Medicine 146: 92–106.

    Article  CAS  PubMed  Google Scholar 

  87. Munmun, F. and P.A. Witt‐Enderby. 2021. Melatonin effects on bone: implications for use as a therapy for managing bone loss. Journal of pineal research e12749.

  88. Favero, G., C. Franco, A. Stacchiotti, L.F. Rodella, and R. Rezzani. 2020. Sirtuin1 role in the melatonin protective effects against obesity-related heart injury. Frontiers in physiology 11: 103.

    Article  PubMed  PubMed Central  Google Scholar 

  89. Xia, L., C. Sun, H. Zhu, M. Zhai, L. Zhang, L. Jiang, P. Hou, J. Li, K. Li, and Z. Liu. 2020. Melatonin protects against thoracic aortic aneurysm and dissection through SIRT1-dependent regulation of oxidative stress and vascular smooth muscle cell loss. Journal of pineal research 69: e12661.

    Article  CAS  PubMed  Google Scholar 

  90. Sasaki, Y., Y. Ikeda, T. Miyauchi, Y. Uchikado, Y. Akasaki and M. Ohishi. 2019. Estrogen-SIRT1 axis plays a pivotal role in protecting arteries against menopause-induced senescence and atherosclerosis. Journal of atherosclerosis and thrombosis 47993.

  91. Karthik, L., G. Kumar, T. Keswani, A. Bhattacharyya, S.S. Chandar, and K. Bhaskara Rao. 2014. Protease inhibitors from marine actinobacteria as a potential source for antimalarial compound. PLoS ONE 9: e90972.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Yaffe, K., E. Vittinghoff, M.J. Pletcher, T.D. Hoang, L.J. Launer, R.A. Whitmer, L.H. Coker, and S. Sidney. 2014. Early adult to midlife cardiovascular risk factors and cognitive function. Circulation 129: 1560–1567.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kodama, S., S. Tanaka, K. Saito, M. Shu, Y. Sone, F. Onitake, E. Suzuki, H. Shimano, S. Yamamoto, K. Kondo, Y. Ohashi, N. Yamada, and H. Sone. 2007. Effect of aerobic exercise training on serum levels of high-density lipoprotein cholesterol: A meta-analysis. Archives of internal medicine 167 (10): 999–1008.

    Article  CAS  PubMed  Google Scholar 

  94. Hodson, L., K. Harnden, R. Banerjee, B. Real, K. Marinou, F. Karpe, and B.A. Fielding. 2014. Lower resting and total energy expenditure in postmenopausal compared with premenopausal women matched for abdominal obesity. Journal of nutritional science 3: e3.

    Article  PubMed  PubMed Central  Google Scholar 

  95. Sanchez-Mateos, S., C. Alonso-Gonzalez, A. Gonzalez, C.M. Martinez-Campa, M.D. Mediavilla, S. Cos, and E.J. Sanchez-Barcelo. 2007. Melatonin and estradiol effects on food intake, body weight, and leptin in ovariectomized rats. Maturitas 58 (1): 91–101.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful to Professor Goncagül Haklar for her guidance in measuring the metabolic parameters in blood samples.

Funding

This study was partly supported by a student grant from The Scientific and Technological Research Council of Turkey (TUBITAK)–program code: 2209, project no: 1919B011900627).

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Authors and Affiliations

  1. Department of Physiology, Marmara University School of Medicine, Basibüyük Mah. Maltepe Basibüyük Yolu No. 9/1, 34854, Maltepe, Istanbul, Turkey

    Sevil Arabacı Tamer, Tülin Altınoluk, Alper Yıldırım & Berrak Ç. Yeğen

  2. Department of Physiology, Sakarya University School of Medicine, Sakarya, Turkey

    Sevil Arabacı Tamer

  3. Department of Physiology, Marmara University Institute of Health Sciences, Istanbul, Turkey

    Sevil Arabacı Tamer & Tülin Altınoluk

  4. Marmara University School of Medicine, Istanbul, Turkey

    Miray Emran, Seda Korkmaz, Rozerin Göze Yüksel, Zeynep Baykal & Zehra Sena Dur

  5. Department of Histology & Embryology, Marmara University School of Medicine, Istanbul, Turkey

    Hilal Nişva Levent & Feriha Ercan

  6. Department of Biochemistry, Faculty of Medicine, Aydın Adnan Menderes University, Aydın, Turkey

    Mürüvvet Abbak Ural & Özge Çevik

  7. Marmara University Vocational School of Health Sciences, Istanbul, Turkey

    Meral Yüksel

Authors
  1. Sevil Arabacı Tamer
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  2. Tülin Altınoluk
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  14. Berrak Ç. Yeğen
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Contributions

All the experiments were performed at Physiology (SAT, TA, ME, SK, RGY, ZB, ZSD, AY, BÇY) and Histology & Embryology (HNL, FE) Departments of School of Medicine, Vocational School of Health Sciences (MY), İstanbul; and Biochemistry (MAU, ÖÇ) Department of School of Medicine at Adnan Menderes University, Aydın, Turkey. All persons (SAT, TA, ME, SK, RGY, ZB, ZSD, HNL, MAU, MY, ÖÇ, FE, AY, BÇY) designated as authors qualify for authorship. All persons who qualify for authorship are listed. All authors agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Study conception and design of the work: SAT, AY, BÇY. Data acquisition: SAT, TA, ME, SK, RGY, ZB, ZSD. Analysis and data interpretation: SAT, TA, ME, SK, RGY, ZB, ZSD, HNL, MAU, MY, ÖÇ, FE, AY, BÇY (all authors). Drafting of the manuscript: SAT, TA, ME, SK, RGY, ZB, ZSD, HNL, MAU, MY, ÖÇ, FE, AY, BÇY (all authors). Critical revision: SAT, AY, BÇY. Approval of the final version of the manuscript: SAT, TA, ME, SK, RGY, ZB, ZSD, HNL, MAU, MY, ÖÇ, FE, AY, BÇY (all authors).

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Correspondence to Berrak Ç. Yeğen.

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Arabacı Tamer, S., Altınoluk, T., Emran, M. et al. Melatonin Alleviates Ovariectomy-Induced Cardiovascular Inflammation in Sedentary or Exercised Rats by Upregulating SIRT1. Inflammation 45, 2202–2222 (2022). https://doi.org/10.1007/s10753-022-01685-2

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  • DOI: https://doi.org/10.1007/s10753-022-01685-2

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