Morphological and biochemical evaluation of effects of Myrtus communis L. extract on heart and aorta in high fat-diet-induced obese rats

Abstract

Objective: The purpose of this study was to examine the protective effects of Myrtus communis L. (MC) extract on high fat-diet (HFD) induced heart and aorta damage by evaluating oxidative stress and the endothelial nitric oxide system (eNOS). Materials and Methods: Wistar albino male rats were divided into 3 groups (n=7) as control, HFD, and HFD+MC. Rats in HFD and HFD+MC groups were HFD fed for 16 weeks and in the last 4 weeks saline or MC (100 mg/kg) was administered orally (5 days/week). Triglyceride, cholesterol, and high-density lipoprotein (HDL) were estimated in blood serum. Tissue oxidative stress and inflammatory parameters were evaluated biochemically. Tissue morphologies, eNOS, inducible NOS (iNOS), and NADPH oxidase-2 (NOX-2)-immunopositive and apoptotic cells were evaluated histologically. Results: Altered serum lipid profiles, degenerated heart, and aorta morphology, increased malondialdehyde, 8‐hydroxy‐2‐ deoxyguanosine, tumor necrosis factor-alpha, monocyte chemoattractant protein-1 and myeloperoxidase levels, and iNOS, NOX-2 immunopositive and apoptotic cells, decreased NO levels, eNOS-immunopositive cells in both tissues were observed in HFD group. All these parameters improved in the HFD+MC group. Conclusion: This study revealed that HFD-induced obesity increased iNOS activation and oxidative stress in the cardiac and aortic tissues of the rats. MC improved oxidant/antioxidant balance and prevented heart and aorta damage via eNOS involvement.

Keywords

• High-fat diet
• Obesity
• Myrtus communis L. extract
• Heart
• Aorta

References

1. [1] World Health Organization. Obesity and overweight. 2021 June 9 (cited 2022 March 12). Available from: https:// www.who.int/newsroom/ fact-sheets/detail/obesity-andoverweight
2. [2] Blüher M. Obesity: Global epidemiology and pathogenesis. Nat Rev Endocrinol 2019; 15(5):288-98. doi: 10.1038/ s41574.019.0176-8
3. [3] Tobore TO, Towards A. Comprehensive theory of obesity and a healthy diet: The causal role of oxidative stress in food addiction and obesity. Behav Brain Res 2020; 384: 112560. doi: 10.1016/j.bbr.2020.112560
4. [4] Manna P, Jain SK. Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: Causes and therapeutic strategies. Metab Syndr Relat Disord 2015; 13: 423-44. https://doi.org/10.1089/met.2015.0095
5. [5] Ndisang JF, Vannacci A, Rastogi S. Oxidative stress and inflammation in obesity, diabetes, hypertension, and related cardiometabolic complications. Oxid Med Cell Longev 2014; 2014:506948. doi: 10.1155/2014/506948
6. [6] Sonta T, Inoguchi T, Tsubouchi H, Sekiguchi N, Kobayashi K, Matsumoto S. Evidence for contribution of vascular NAD(P) H oxidase to increased oxidative stress in animal models of diabetes and obesity. Free Radic Biol Med 2004; 37:115–23. doi: 10.1016/j.freeradbiomed.2004.04.001
7. [7] Acikel Elmas M, Cakıcı SE, Dur IR, et al. Protective effects of exercise on heart and aorta in high-fat diet-induced obese rats. Tissue Cell 2019; 57:57-65. https://doi.org/10.1111/jfbc.12297
8. [8] Gamez-Mendez AM, Vargas-Robles H, Ríos A, Escalante B. Oxidative stress-dependent coronary endothelial dysfunction in obese mice. PloS One 2015; 10:e0138609. doi:10.1371/ journal.pone.0138609

9. [9] Sukumar P, Viswambharan H, Imrie H, Cubbon RM, Yuldasheva N, Gage M. NADPH oxidase has a critical role in insulin resistance-related endothelial cell dysfunction. Diabetes 2013; 62:2130–134. doi: 10.2337/db12-1294
10. [10] Silver AE, Beske SD, Christou DD, Donato AJ, Moreau KL, Eskurza I. Overweight and obese humans demonstrate increased vascular endothelial NAD(P)H oxidasep47phox expression and evidence of endothelial oxidative stress. Circulation 2007; 115:627–63. doi: 10.1161/ CIRCULATIONAHA.106.657486
11. [11] Elmas MA, Ozakpinar OB, Kolgazi M, Sener G, Ercan F.Morphological and biochemical investigation of the healingeffects of exercise on high fat diet induced kidney and bladderdamage. Clin Exp Health Sci 2022; 12: 817 -23. doi: 10.33808/clinexphealthsci.1027516
12. [12] Hoogeveen RC, Morrison A, Boerwinkle E, et al. Plasma MCP-1 level and risk for peripheral arterial disease and incident coronary heart disease: Atherosclerosis Risk in Communities study. Atherosclerosis 2005; 183:301-7. doi: 10.1016/j.atherosclerosis.2005.03.007
13. [13] Engin A. Endothelial dysfunction in obesity. Adv Exp Med Biol 2017; 960:345-79. doi: 10.1007/978-3-319-48382-5_15
14. [14] Silva JF, Correa IC, Diniz TF, et al. 2016. Obesity, inflammation, and exercise training: Relative contribution of iNOS and eNOS in the modulation of vascular function in the mouse aorta. Front Physiol 2016; 7:386. doi: 10.3389/fphys.2016.00386
15. [15] Patra S, Nithya S. Review of medicinal plants for antiobesity activity. Transl Biomed 2015; 6:1-22. https://doi. org/10.21767/2172-0479.100021
16. [16] Alipour G, Dashti S, Hosseinzadeh H. Review of pharmacological effects of Myrtus communis L. and its active constituents. Phytother Res 2014; 28:1125-36. doi: 10.1002/ ptr.5122
17. [17] Kanpalta F, Ertas B, Sen A, Akakin D, Sener G, Ercan F. Myrtus communis L. extract amelioarates high fat diet induced kidney and bladder damage by inhibiting oxidative stress and inflammation. Eur J Biol 2022; 81: 217-30. doi: 10.26650/ EurJBiol.2022.111.1191
18. [18] Kuru Yaşar R, Kuru D, Şen A, Şener G, Ercan F, Yarat A. Effects of Myrtus communis L. extract and apocynin on lens oxidative damage and boron levels in rats with a high fatdiet. Turk J Ophthalmol 2021; 51: 344-50. doi: 10.4274/tjo. galenos.2021.27981
19. [19] Khan R, Feroz Z, Jamil M, Ahmed M. Hypolipidemic and Antithrombotic evaluation of Myrtus communis L. in cholesterol-fed rabbits. Afr J Pharm Pharmacol 2014; 8:235- 39. doi: 10.5897/AJPP2013.3488
20. [20] Arslan S, Ozcan O, Gurel-Gokmen B, et al. Myrtle improves renovascular hypertension-induced oxidative damage in heart, kidney, and aortic tissue. Biologia 2022; 77: 1877-88. doi: 10.1007/s11756.022.01039-1
21. [21] Sen A, Yuksel M, Bulut G, et al. Therapeutic potential of Myrtus communis subsp. communis extract against acetic acidinduced colonic inflammation in rats. J Food Biochem 2017; 41: e12297. https://doi.org/10.1111/jfbc.12297
22. [22] Sener G, Toklu H, Kapucu C, et al. Melatonin protects against oxidative organ injury in a rat model of sepsis. Surg Today 2005; 35: 52 – 9. doi: 10.1007/s00595.004.2879-1
23. [23] Hamblin M, Chang L, Zhang H, Yang K, Zhang J, Chen YE. Vascular smooth muscle cell peroxisome proliferator-activated receptor-γ deletion promotes abdominal aortic aneurysms. J Vasc Surg 2010; 52:984-93. doi: 10.1016/j.jvs.2010.05.089
24. [24] Ahmed AH. Flavonoid content and antiobesity activity of leaves of Myrtus communis. Asian J Chem 2013; 25: 6818–22. https://doi.org/10.14233/ajchem.2013.14823
25. [25] Yu HT, Fu X, Liang B, et al. Oxidative damage of mitochondrial respiratory chain in different organs of a rat model of dietinduced obesity. Eur J Nutr 2018; 57: 1957-67. doi: 10.1007/ s00394.017.1477-0
26. [26] Hariri N, Thibault L. High-fat diet-induced obesity in animal models. Nutr Res Rev 2010; 23: 270-99. doi: 10.1017/ S095.442.2410000168
27. [27] Tuzcu Z, Orhan C, Sahin N, Juturu V, Sahin K. Cinnamon polyphenol extract inhibits hyperlipidemia and inflammation by modulation of transcription factors in high-fat dietfed rats. Oxid Med Cell Longev 2017; 1583098. doi: 10.1155/2017/1583098
28. [28] Mabrouki L, Rjeibi I, Taleb J, Zourgui L. Cardiac ameliorative effect of Moringa Oleifera leaf extract in high-fat diet-induced obesity in rat model. Biomed Res Int 2020; 7:6583603. doi: 10.1155/2020/6583603.
29. [29] Rosa A, Deiana M, Casu V, et al. Antioxidant activity of oligomeric acylphloroglucinols from Myrtus communis L. Free Radic Res 2003; 37: 1013-19.
30. [30] Rossi A, Di Paola R, Mazzon E, et al. Myrtucommulonefrom Myrtus communis exhibits potent anti-inflammatoryeffectiveness in vivo. J Pharmacol Exp Ther 2009; 329: 76-86.
31. [31] Kumral ZN, Sener G, Ozgur S, et al. Regular exercise alleviates renovascular hypertension-induced cardiac/endothelial dysfunction and oxidative injury in rats. J Physiol Pharmacol 2016; 67: 45-55
32. [32] Ritchie RH, Drummond GR, Silva S, Kemp-Harper BK. The opposing roles of NO and oxidative stress in cardiovascular disease. Pharmacol Res 2017; 116:57-69. doi: 10.1016/j. phrs.2016.12.017
33. [33] Skrzep-Poloczek B, Poloczek J, Chełmecka E, et al. The Oxidative stress markers in the erythrocytes and heart muscle of obese rats: Relate to a high-fat diet but not to DJOS bariatric surgery. Antioxidants 2020; 9:183. doi: 10.3390/antiox9020183
34. [34] Godo S, Shimokawa H. Divergent roles of endothelial nitric oxide synthases system in maintaining cardiovascular homeostasis. Free Radic Biol Med 2017; 109:4-10. doi: 10.1016/j.freeradbiomed.2016.12.019.
35. [35] Ritchie RH, Drummond GR, Silva S, Kemp-Harper BK. The opposing roles of NO and oxidative stress in cardiovascular disease. Pharmacol Res 2017; 116:57-69. doi: 10.1016/j. phrs.2016.12.017
36. [36] Sen A, Ozkan S, Recebova K, et al. Effects of Myrtus communis extract treatment in bile duct ligated rats. J Surg Res 2016;205: 359–67. https://doi.org/10.1016/j.jss.2016.06.094
37. [37] Wang X, Zhao S, Su M, Sun L, et al. Geraniol improves endothelial function by inhibiting NOX-2 derived oxidative stress in high fat diet fed mice. Biochem Biophys Res Commun 2016; 474: 182-7. doi: 10.1016/j.bbrc.2016.04.097
38. [38] Ma Y, Li H, Yue Z, et al. Cryptotanshinone attenuates cardiac fibrosis via downregulation of COX-2, NOX-2, and NOX- 4. J Cardiovasc Pharmacol 2014; 64:28-37. doi: 10.1097/ FJC.000.000.0000000086
39. [39] Du J, Fan LM, Mai A, Li JM. Crucial roles of Nox2-derived oxidative stress in deteriorating the function of insulin receptors and endothelium in dietary obesity of middleaged mice. Br J Pharmacol 2013; 170 :1064–77. doi: 10.1111/ bph.12336
40. [40] Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol 2011; 29: 415-45. https://doi. org/10.1146/annurev-immunol-031.210.101322
41. [41] Hunter AL, Choy JC, Granville DJ. Detection of apoptosis in cardiovascular diseases. Methods Mol Med 2005; 112:277-89. doi: 10.1385/1-59259-879-x:277
42. [42] Maciejczyk M, Zebrowska E, Zalewska A, Chabowski A. Redox balance, antioxidant defense, and oxidative damage in the hypothalamus and cerebral cortex of rats with high fat diet-induced insulin resistance. Oxid Med Cell Longev 2018; 6:6940515. doi: 10.1155/2018/6940515
43. [43] Valavanidis A, Vlachogianni T, Fiotakis C. 8-hydroxy- 2’-deoxyguanosine (8-OHdG): A critical biomarker of oxidative stress and carcinogenesis. J Environ Sci Health C Environ Carcinog Ecotoxicol Rev 2009; 27:120-39. doi: 10.1080/105.905.00902885684.
44. [44] Kalpana Ballal, Christopher R Wilson, Romain Harmancey, Heinrich Taegtmeyer. Obesogenic high fat western diet induces oxidative stress and apoptosis in rat heart. Mol Cell Biochem 2010; 344:221-30. doi: 10.1007/s11010.010.0546-y
45. [45] Xu Z, Qin Y, Lv B, Tian Z, Zhang B. Intermittent fasting improves high-fat diet-induced obesity cardiomyopathy via alleviating lipid deposition and apoptosis and decreasing m6A methylation in the heart. Nutrients 2022; 14:251. doi: 10.3390/ nu14020251
46. [46] Morton LW, Caccetta RAA, Puddey IB, Croft KD. Chemistry and biological effects of dietary phenolic compounds: relevance to cardiovascular disease. Clin Exp Pharmacol Physiol 2000; 27:152-59. doi: 10.1046/j.1440-1681.2000.03214.x.