:: Volume 22, Issue 5 (Bimonthly 2018) ::
Feyz 2018, 22(5): 469-477 Back to browse issues page
The effect of combined therapy with resveratrol, and continuous and interval exercises on levels of apoptotic biomarkers in heart tissue of male rats with non-alcoholic fatty liver
Hossein Mahdian , Parvin Farzanegi , Amin Farzaneh-Hessari
Department of Exercise Physiology, Sari Branch, Islamic Azad University, Sari, I.R. Iran. , Parvin.farzanegi@gmail.com
Abstract:   (3322 Views)
Background: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases. This study aimed at evaluating the effects of therapy with resveratrol supplementation alone or in combination with exercise trainings on cardiomyocytes apoptosis in a heart tissue of rats with NAFLD.
Materials and Methods: In this experimental study, a total of 56 male Wistar rats were divided into control and seven experimental NAFLD groups including, patient, saline, resveratrol (RSV), continuous exercise, interval exercise, continuous exercise+RSV, and interval exercise+RSV. Apoptosis biomarkers, including Bax and Bcl2 levels, were measured in the heart of all groups using specific ELISA kits.
Results: The Bax levels in the heart tissue of the patient and saline groups were 29.95±5.83 and 28.37±5.83 ng/mg/protein, respectively, which were significantly higher than those in other groups (P<0.0001), while the Bcl2 concentration was significantly decreased (P<0.0001). The mean ratios of Bax/Bcl2 in the patient (23.02±7.65) and saline (20.43±5.29) groups were significantly higher than those in the other groups (P<0.001). Resveratrol supplementation alone or in combination with exercise trainings significantly decreased the cardiac Bax content, but significantly increased the cardiac Bcl2 level (P<0.001).
Conclusion: Non-alcoholic fatty liver disease is associated with increased apoptotic biomarkers in heart cells. Although resveratrol alone has an anti-apoptotic properties, combined therapy with interval and continuous trainings can be more effective.
Keywords: Apoptosis, Non-alcoholic fatty liver, Interval and continuous training, Resveratrol
Full-Text [PDF 223 kb]   (1112 Downloads)    
Type of Study: Research | Subject: General
Received: 2018/05/3 | Revised: 2018/12/3 | Accepted: 2018/09/23 | Published: 2018/11/28
1. Hardy T, McPherson S. NAFLD in Asia-clinical associations with advanced disease become clearer. Aliment Pharmacol Ther 2018; 47(7): 1035-6.
2. Mann JP, Raponi M, Nobili V. Clinical implications of understanding the association between oxidative stress and pediatric NAFLD. Expert Rev Gastroenterol Hepatol 2017; 11(4): 371-82.
3. Adams J, Cory S. Bcl-2-regulated apoptosis: mechanism and therapeutic potential. Curr Opin Immunol 2007; 19(5): 488-96.
4. Er E, Oliver L, Cartron P, Juin P, Manon S, Vallette F. Mitochondria as the target of the pro-apoptotic protein Bax. Biochim Biophys Acta 2006; 1757(9-10): 1301-11.
5. Taylor RC, Cullen SP, Martin SJ, Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol 2008; 9(3): 231-41.
6. Roberts EA. Non-alcoholic fatty liver disease (NAFLD) in children. Front Biosci 2005; 10: 2306-18.
7. Henao-Mejia J, Elinav E, Jin C, Hao L, Mehal WZ, Strowig T, et al. Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity. Nature 2012; 482(7384): 179-85.
8. Inoue H, Kishimoto A, Ushikoshi-Nakayama R, Hasaka A, Takahashi A, Ryo K, et al. Resveratrol improves salivary dysfunction in a non-obese diabetic (NOD) mouse model of Sjogren's syndrome. J Clin Biochem Nutr 2016; 59(2): 107-12.
9. Park HG, Lee YR, Jun JK, Lee WL. Exercise training is more effective than resveratrol supplementation on alleviation of inflammation in peritoneal macrophages of high fat diet mice. J Exerc Nutrition Biochem 2014; 18(1): 79-87.
10. Shojaee-Moradie F, Cuthbertson DJ, Barrett M, Jackson N, Herring R, Thomas E, et al. Exercise Training Reduces Liver Fat and Increases Rates of VLDL Clearance But Not VLDL Production in NAFLD. J Clin Endocrinol Metab 2016; 101(11): 4219–28.
11. Lanzilli G, Cottarelli A, Nicotera G, Guida S, Ravagnan G, Fuggetta MP. Anti-inflammatory effect of resveratrol and polydatin by in vitro IL-17 modulation. Inflammation 2012; 35(1): 240-8.
12. Wenbin Z, Guojun G. Resveratrol Ameliorates Diabetes-induced Renal Damage through Regulating the Expression of TGF-beta1, Collagen IV and Th17/Treg-related Cytokines in Rats. West Indian Med J 2014; 63(1): 20-5.
13. Voduc N, la Porte C, Tessier C, Mallick R, Cameron DW. Effect of resveratrol on exercise capacity: a randomized placebo-controlled crossover pilot study. Appl Physiol Nutr Metab 2014; 39(10): 1183-7.
14. Wang D, Li SP, Fu JS, Bai L, Guo L. Resveratrol augments therapeutic efficiency of mouse bone marrow mesenchymal stem cell-based therapy in experimental autoimmune encephalomyelitis. Int J Dev Neurosci 2016; 49: 60-6.
15. Zheng Y, Zhao Z, Wu W, Song C, Meng S, Fan L, et al. Effects of dietary resveratrol supplementation on hepatic and serum pro-/anti-inflammatory activity in juvenile GIFT tilapia, Oreochromis niloticus. Dev Comp Immunol 2017; 73: 220-8.
16. Yang DH, Lou ZH, Cheng B, Zhang GJ, Wang YP, Xu H. Effects of lotus leaf on inflammatory factors and liver AdipoR2 expressions in rats with NAFLD induced by high fat diet and high glucose. Zhongguo Zhong Yao Za Zhi 2016; 41(18): 3406-3411.
17. Wu RE, Huang WC, Liao CC, Chang YK, Kan NW, Huang CC, Resveratrol protects against physical fatigue and improves exercise performance in mice. Molecules 2013; 18(4): 4689-702.
18. Wang ZM, Chen YC, Wang DP. Resveratrol, a natural antioxidant, protects monosodium iodoacetate-induced osteoarthritic pain in rats. Biomed Pharmacother 2016; 83: 763-70.
19. Zhao Y, Song W, Wang Z, Wang Z, Jin X, Xu J, et al. Resveratrol attenuates testicular apoptosis in type 1 diabetic mice: Role of Akt-mediated Nrf2 activation and p62-dependent Keap1 degradation. Redox Biol 2018; 14: 609-17.
20. Efati M, Khorrami M, Zarei Mahmmodabadi A, Raouf Sarshoori J. Induction of an Animal Model of Non-Alcoholic Fatty Liver Disease Using a Formulated High-Fat Diet. J Babol Univ Med Sci 2016; 18: 57-62.
21. Hajighasem A, Farzanegi P, Mazaheri Z. Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease. Arch Physiol Biochem 2018; 20: 1-8.
22. Batacan RB, Jr., Duncan MJ, Dalbo VJ, Connolly KJ, Fenning AS. Light-intensity and high-intensity interval training improve cardiometabolic health in rats. Appl Physiol Nutr Metab 2016; 41(9): 945-52.
23. Freitas DA, Rocha-Vieira E, Soares BA, Nonato LF, Fonseca SR, Martins JB, et al. High intensity interval training modulates hippocampal oxidative stress, BDNF and inflammatory mediators in rats. Physiol Behav 2017; 184: 6-11.
24. Alamdari N, Aversa Z, Castillero E, Gurav A, Petkova V, Tizio S, et al. Resveratrol prevents dexamethasone-induced expression of the muscle atrophy-related ubiquitin ligases atrogin-1 and MuRF1 in cultured myotubes through a SIRT1-dependent mechanism. Biochem Biophys Res Commun 2012; 417(1): 528-33.
25. Pollack M, Phaneuf S, Dirks A, Leeuwenburgh C. The role of apoptosis in the normal aging brain, skeletal muscle, and heart. Ann N Y Acad Sci 2002; 959: 93-107.
26. Wang CC, Lin SK, Tseng YF, Hsu CS, Tseng TC, Lin HH, et al. Elevation of serum aminotransferase activity increases risk of carotid atherosclerosis in patients with non-alcoholic fatty liver disease. J Gastroenterol Hepatol 2009; 24(8): 1411-6.
27. Shaikh AH, Aatif S, Ahmed T. Carotid Intima-Media Thickness in Patients with Non-Alcoholic Fatty Liver Disease. J Basic Appl Sci 2013; 9: 333.
28. Vlachopoulos C, Manesis E, Baou K, Papatheodoridis G, Koskinas J, Tiniakos D, et al. Increased arterial stiffness and impaired endothelial function in nonalcoholic Fatty liver disease: a pilot study. Am J Hypertens 2010; 23(11): 1183-9.
29. Caserta CA, Pendino GM, Amante A, Vacalebre C, Fiorillo MT, Surace P, et al. Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. Am J Epidemiol 2010; 171(11): 1195-202.
30. Paiva AA, Raposo HF, Wanschel AC, Nardelli TR, Oliveira HC. Apolipoprotein CIII Overexpression-Induced Hypertriglyceridemia Increases Nonalcoholic Fatty Liver Disease in Association with Inflammation and Cell Death. Oxid Med Cell Longev 2017; 2017: 1838679.
31. Huang CZ, Tung YT, Hsia SM, Wu CH, Yen GC. The hepatoprotective effect of Phyllanthus emblica L. fruit on high fat diet-induced non-alcoholic fatty liver disease (NAFLD) in SD rats. Food Funct 2017; 8(2): 842-50.
32. Fealy C, Haus J, Solomon T, Pagadala M, Flask C, Mc-Cullough A. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. J Appl Physiol Behav 1985; 113(1): 1-6.
33. Thong-Ngam D, Samuhasaneeto S, Kulaputana O, Klaikeaw N. N-acetylcysteine attenuates oxidative stress and liver pathology in rats with non-alcoholic steatohepatitis. World J Gastroenterol 2007; 13(38): 5127-32.
34. Kumar A, Sharma A, Duseja A, Das A, Dhiman RK, Chawla YK, et al. Patients with Nonalcoholic Fatty Liver Disease (NAFLD) have Higher Oxidative Stress in Comparison to Chronic Viral Hepatitis. J Clin Exp Hepatol 2013; 3(1): 12-8.
35. Liao ZY, Chen JL, Xiao MH, Sun Y, Zhao YX, Pu D, et al. The effect of exercise, resveratrol or their combination on Sarcopenia in aged rats via regulation of AMPK/Sirt1 pathway. Exp Gerontol 2017; 98: 177-83.
36. Liu H, Lu HY. Nonalcoholic fatty liver disease and cardiovascular disease. World J Gastroenterol 2014; 20(26): 8407-15.
37. Tian Y, Ma J, Wang W, Zhang L, Xu J, Wang K, et al. Resveratrol supplement inhibited the NF-kappaB inflammation pathway through activating AMPKalpha-SIRT1 pathway in mice with fatty liver. Mol Cell Biochem 2016; 422(1-2): 75-84.
38. Sevov M, Elfineh L, Cavelier LB. Resveratrol regulates the expression of LXR-alpha in human macrophages. Biochem Biophys Res Commun 2006; 348(3): 1047-54.
39. Tofighi A, Ebrahimi Kalan A, Jamali Qarakhanlou BJ. The effect of resveratrol supplementation and aerobic training on cardiac tissue alteration of rats with acute myocardial infarction. Iran J Physiol Pharmacol 2017; 1: 211-21.
40. Wang H, Jiang T, Li W, Gao N, Zhang T. Resveratrol attenuates oxidative damage through activating mitophagy in an in vitro model of Alzheimer's disease. Toxicol Lett 2018; 282: 100-8.
41. Jeong JH, Lee YR, Park HG, Lee WL. The effects of either resveratrol or exercise on macrophage infiltration and switching from M1 to M2 in high fat diet mice. J Exerc Nutrition Biochem 2015; 19(2): 65-72.
42. Faghihzadeh F, Adibi P, Rafiei R, Hekmatdoost A. Resveratrol supplementation improves inflammatory biomarkers in patients with nonalcoholic fatty liver disease. Nutr Res 2014; 34(10): 837-43.
43. Tung BT, Rodriguez-Bies E, Ballesteros-Simarro M, Motilva V, Navas P, Lopez-Lluch G. Modulation of endogenous antioxidant activity by resveratrol and exercise in mouse liver is age dependent. J Gerontol A Biol Sci Med Sci 2014; 69(4): 398-409.
44. Fealy CE, Haus JM, Solomon TP, Pagadala M, Flask CA, McCullough AJ, et al. Short-term exercise reduces markers of hepatocyte apoptosis in nonalcoholic fatty liver disease. J Appl Physiol (1985) 2012; 113(1): 1-6.
45. Tung BT, Rodriguez-Bies E, Thanh HN, Le-Thi-Thu H, Navas P, Sanchez VM, et al. Organ and tissue-dependent effect of resveratrol and exercise on antioxidant defenses of old mice. Aging Clin Exp Res 2015; 27(6): 775-83.

XML   Persian Abstract   Print

Creative Commons License
This open access journal is licensed under a Creative Commons Attribution-NonCommercial ۴.۰ International License. CC BY-NC ۴. Design and publishing by Kashan University of Medical Sciences.
Copyright ۲۰۲۳© Feyz Medical Sciences Journal. All rights reserved.
Volume 22, Issue 5 (Bimonthly 2018) Back to browse issues page