Document Type : Research Paper

Authors

1 Department of Exercise Physiology, Faculty of Sport Sciences, Ferdowsi University of Mashhad, Mashhad, Iran

2 Ferdowsi University of Mashhad, Department of Exercise Physiology, Faculty of Sport Sciences, Mashhad, Iran

3 Neuroscience Research Center, Neuropharmacology Institute, Kerman University of Medical Sciences, Kerman, Iran.

Abstract

Polyploid nuclei are formed as a result of a defective cell division cycle, which is strongly associated with the aging process and leads to an increase in the area of  hepatocytes, i.e. cell inflammation. The purpose of this study was to evaluate the effect of a period high-intensity interval training (HIIT) swimming with resveratrol (R) supplementation on the area of liver cells and polyploid nuclei in aged rats. In this study, 40 male Wistar aged rats (twenty-month-old, weight of 350-450 g) that the NOVEL test of whom was negative and had no motor disorder, were divided into five groups (control (C), HIIT training (HIT), supplement and HIIT training (HITR), supplement (R), Solvent (S). Rats in the (HIT) and (HITR) groups performed (HIIT) swimming for six weeks (three days a week) the initial load applied (in the first week) was 9% of body weight per rat and 1% was added every week. Also, eight young rats (three-month-old, weight of 150-180 g) was placed in a group(Y) for comparison. At the end of the protocol and after biopsy, 5 healthy tissues were obtained from each group. Variables were stained with Hematoxylin and Eosin (HE) and, ImageJ software was used to calculate the area of hepatocyte and one-way analysis of variance and Tukey’s post hoc test were used to compare the groups. After six weeks of HIIT swimming with and without resveratrol, there was a significant decrease between the mean levels of hepatocytes in the study groups, which was significant in the training group compared to the other groups. However, this change in polyploid nuclei was not significant (p ≤0.05). There was a significant difference between the mean area of hepatocytes in the research groups (P=0.0001) (Table 1). According to Figure 1, Tukey’s test showed that this significant difference was in the mean area of hepatocytes between the control and exercise (P=0.0001), control and youth (P=0.0001), solvent and supplement (P=0.012), solvent and training (P=0.0001), solvent and youth (P=0.0001), supplement and training + supplement (P=0.0001), supplement and training (P=0.002), supplement and youth (P=0.003), training + supplement and training (P=0.0001), and training + supplement and youth groups (P=0.0001). There was no significant difference between the other groups. It seems HIIT swimming exercise with resveratrol supplements can lower liver cell levels.

Keywords

  1. Niccoli T, Partridge L. Ageing as a risk factor for disease. Current Biology. 2012 Sep 11;22(17):R741-52.
  2. Kennedy BK, Berger SL, Brunet A, Campisi J, Cuervo AM, Epel ES, Franceschi C, Lithgow GJ, Morimoto RI, Pessin JE, Rando TA. Geroscience: linking aging to chronic disease. Cell. 2014 Nov 6;159(4):709-13.
  3. Rui L. Energy metabolism in the liver. Comprehensive physiology. 2014 Jan;4(1):177.
  4. Hunt NJ, Kang SW, Lockwood GP, Le Couteur DG, Cogger VC. Hallmarks of aging in the liver. Computational and Structural Biotechnology Journal. 2019 Aug 7.
  5. Gong Z, Tas E, Yakar S, Muzumdar R. Hepatic lipid metabolism and non-alcoholic fatty liver disease in aging. Molecular and cellular endocrinology. 2017 Nov 5; 455:115-30.
  6. Timchenko NA. Aging and liver regeneration. Trends in Endocrinology & Metabolism. 2009 May 1;20(4):171-6.
  7. Kim H, Kisseleva T, Brenner DA. Aging and liver disease. Current opinion in gastroenterology. 2015 May;31(3):184.
  8. Fontana K, Aldrovani M, Paoli FD, Oliveira HC, Campos Vidal BD, da Cruz Hoflingl MA. Hepatocyte nuclear phenotype, the cross-talk between anabolic androgenic steroids and exercise in transgenic mice. Histology and histopathology. 2008.
  9. 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.
  10. 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.
  11. Little JP, Jung ME, Wright AE, Wright W, Manders RJ. Effects of high-intensity interval exercise versus continuous moderate-intensity exercise on postprandial glycemic control assessed by continuous glucose monitoring in obese adults. Applied physiology, nutrition, and metabolism. 2014 Feb 18;39(7):835-41.
  12. Cassidy S, Thoma C, Houghton D, Trenell MI. High-intensity interval training: a review of its impact on glucose control and cardiometabolic health. Diabetologia. 2017;60(1):7-23.
  13. Huang CC, Chiang WD, Huang WC, Huang CY, Hsu MC, Lin WT. Hepatoprotective effects of swimming exercise against D-galactose-induced senescence rat model. Evidence-Based Complementary and Alternative Medicine. 2013;Oct ;2013.
  14. Faghihzadeh F, Hekmatdoost A, Adibi P. Resveratrol and liver: a systematic review. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences. 2015;20(8):797.
  15. 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.
  16. Monserrat Hernández‐Hernández E, Serrano‐García C, Antonio Vázquez‐Roque R, Díaz A, Monroy E, Rodríguez‐Moreno A, et al. Chronic administration of resveratrol prevents morphological changes in prefrontal cortex and hippocampus of aged rats. Synapse. 2016;70(5):206-17.
  17. Dutt Way W, Soga T, Parhar IS. Aging and chronic administration of serotonin-selective reuptake inhibitor citalopram upregulate Sirt4 gene expression in the preoptic area of male mice. Frontiers in Genetics. 2015;6:281.
  18. Farzanegi P, Habibian M, Alinejad H. The combined effect of regular aerobic exercise with garlic extract on renal apoptosis regulatory factors in aged rats with chronic kidney disease. J Arak Uni Med Sci. 2016;19(3):62-70.
  19. Terada S, Yokozeki T, Kawanaka K, Ogawa K, Higuchi M, Ezaki O, Tabata I. Effects of high-intensity swimming training on GLUT-4 and glucose transport activity in rat skeletal muscle. Journal of Applied Physiology. 2001;90(6):2019-24.
  20. Ramos-Filho D, Chicaybam G, de-Souza-Ferreira E, Martinez CG, Kurtenbach E, Casimiro-Lopes G, et al. High intensity interval training (HIIT) induces specific changes in respiration and electron leakage in the mitochondria of different rat skeletal muscles. PloS One. 2015;10(6):e0131766.
  21. Casimiro-Lopes G, Ramos D, Sorenson MM, Salerno VP. Redox balance and mitochondrial glycerol phosphate dehydrogenase activity in trained rats. European Journal of Applied Physiology. 2012;112(11):3839-46.
  22. Shadfar S, Couch ME, McKinney KA, Weinstein LJ, Yin X, Rodríguez JE, et al. Oral resveratrol therapy inhibits cancer-induced skeletal muscle and cardiac atrophy in vivo. Nutrition and Cancer. 2011;63(5):749-62.
  23. Ungvari Z, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith K, et al. Increased mitochondrial H2O2 production promotes endothelial NF-κB activation in aged rat arteries. American Journal of Physiology-Heart and Circulatory Physiology. 2007;293(1):H37-47.
  24. Shafiee A, kordi M, Gaeini A, Soleimani M, Nekouei A, Hadidi V. The effect of eight week of high intensity interval training on expression of mir-210 and ephrinA3 mrna in soleus muscle healthy male rats. J Arak Uni Med Sci. 2014;17(3):26-34
  25. Marosi K, Bori Z, Hart N, Sárga L, Koltai E, Radák Z, et al. Long-term exercise treatment reduces oxidative stress in the hippocampus of aging rats. Neuroscience. 2012;226:21-8.
  26. 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. Archives of Physiology and Biochemistry. 2019;125(2):142-9.
  27. Kinoshita S, Yano H, Tsuji E. An increase in damaged hepatocytes in rats after high intensity exercise. Acta Physiologica Scandinavica. 2003;178(3):225-30.
  28. Dörnen J, Sieler M, Weiler J, Keil S, Dittmar T. Cell fusion-mediated tissue regeneration as an inducer of polyploidy and aneuploidy. International Journal of Molecular Sciences. 2020;21(5):1811.
  29. Schmucker DL, Sanchez H. Liver regeneration and aging: a current perspective. Current Gerontology and Geriatrics Research. 2011 Oct ;2011.
  30. Nucci RA, Teodoro AC, Krause Neto W, Silva WD, de Souza RR, Anaruma CA, et al. Effects of resistance training on liver structure and function of aged rats. The Aging Male. 2018;21(1):60-4.
  31. Vitaglione P, Morisco F, Caporaso N, Fogliano V. Dietary antioxidant compounds and liver health. Critical Reviews in Food Science and Nutrition. 2005;44(7-8):575-86.
  32. Alberdi G, Rodríguez VM, Macarulla MT, Miranda J, Churruca I, Portillo MP. Hepatic lipid metabolic pathways modified by resveratrol in rats fed an obesogenic diet. Nutrition. 2013;29(3):562-7.
  33. Cho SJ, Jung UJ, Choi MS. Differential effects of low-dose resveratrol on adiposity and hepatic steatosis in diet-induced obese mice. British journal of nutrition. 2012;108(12):2166-75.
  34. Schmatz R, Perreira LB, Stefanello N, Mazzanti C, Spanevello R, Gutierres J, et al. Effects of resveratrol on biomarkers of oxidative stress and on the activity of delta aminolevulinic acid dehydratase in liver and kidney of streptozotocin-induced diabetic rats. Biochimie. 2012;94(2):374-83.
  35. 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.
  36. Heidari Shahreza A. Azamian Jazi A. Bani Talebi E. Palizban AA. Effect of Low-Intensity Endurance Training and High Intensity Interval Training on HIG2 Gene Expression and Visceral Adipose Tissue Triglyceride Content in NAFLD Rats. Sports Physiology. 1400; 13 (50): 87-110. (In Persian).
  37. Petta S, Muratore C, Craxi A. Non-alcoholic fatty liver disease pathogenesis: the present and the future. Digestive and Liver Disease. 2009;41(9):615-25.
  38. Nucci RA, Teodoro AC, Gama EF. Liver regeneration and aging: a review. Journal of Morphological Sciences. 2016;33(04):179-82.
  39. Nakamoto H, Kaneko T, Tahara S, Hayashi E, Naito H, Radak Z, et al. Regular exercise reduces 8-oxodG in the nuclear and mitochondrial DNA and modulates the DNA repair activity in the liver of old rats. Experimental Gerontology. 2007;42(4):287-95.
  40. Wilkinson PD, Delgado ER, Alencastro F, Leek MP, Roy N, Weirich MP, et al. The polyploid state restricts hepatocyte proliferation and liver regeneration in mice. Hepatology. 2019;69(3):1242-58.
  41. Wang MJ, Chen F, Lau JT, Hu YP. Hepatocyte polyploidization and its association with pathophysiological processes. Cell Death & Disease. 2017;8(5):e2805.