The effect of eight weeks aerobic exercise after injection of bone marrow-derived stem cells on TNF-α and NF-KB of liver tissue in rats model of Non-alcoholic fatty liver

Subject Areas : Sport Sciences Quarterly

hamed Namdar ¹ , Seyed Abdollah Hashemvarzi ² , عبدالرضا جعفری ³

1 - Ph.D Candidate in Exercise Physiology, Department of Exercise Physiology, Faculty of Humanities, Sari Branch, Islamic Azad University, Sari, Iran
2 -
3 - عضو هیئت علمی/ دانشگاه آزاد اسلامی واحد ساری

Received: 2024-09-27 Accepted : 2025-01-05 Published : 2025-04-08

Keywords: Exercise, Stem cell, Inflammation, Non-alcoholic fatty liver,

Abstract :

Non-alcoholic fatty liver disease is one of the most common liver diseases of this century, which is associated with changes in inflammatory cytokines. 36 adult male Wistar rats were divided into two main groups: control (6 rats) and patients with fatty liver (30 rats). The control group used standard food for 6 weeks, but the animals in the diseased groups used high-fat food to induce fatty liver disease. At the end of the sixth week, to confirm the development of fatty liver disease, blood was randomly drawn from the tails of 3 rats and liver enzymes were measured. Then the animals of the patient groups were randomly divided into 5 groups: Saline, Fatty liver, Exercise, Cell, Exercise + Cell. About 10⁵ cells in 2 microliters of environment were injected into the cell receiving groups for each rat through the tail vein. The exercise program consisted of 8 weeks of treadmill running, incrementaly.  TNF-α and NF-KB decreased, but these changes were significant only in the groups of exercise and exercise + cells compared to the fatty liver group. Incremental aerobic training after the injection of bone marrow-derived stem cells decreased the inflammatory index of TNF-α and NF-KB in rats with Non-alcoholic fatty liver. Therefore, it seems that this method can be considered as a therapeutic solution and improve liver condition

References:

Bina Kumari Mehta, Kaushal Kumar Singh, Sugato Banerjee. Effect of exercise on type 2 diabetes-associated cognitive impairment in rats. International Journal of Neuroscience 2019; 129(3): 252-263.
Capitelli CS, Lopes CS, Alves AC, Barbiero J, Oliveira LF, Silva V, Vital M. Opposite Effects of Bone Marrow-Derived Cells Transplantation in MPTP-rat Model of Parkinson’s Disease: A Comparison Study of Mononuclear and Mesenchymal Stem Cells. Int J Med Sci 2014; 11(10): 1049-106.
Chalasani N, Younossi Z, Lavine E J, Diehel M A, Brunt M E, Cusi K, et al. The Diagnosis and Management of Non-alcoholic Fatty Liver Disease: Practice Guideline by the American Gastroenterological Association, American Association for the Study of Liver Diseases, and American College of Gastroenterology 2012 by the AGA Institute. Am J Gastroenterol 2012. (142):1592–609.
Cotman CW, Berchtold NC, Christie L. Exercise builds brain health: key roles of growth factor cascades and inflammation. Trends in neurosciences 2007; 30(9): 464-472.
Efati M, Khorrami M, Zarei Mahmmudabadi 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 2017;18(11):57-62 (Persian).
Farzanegi P, Dana A, Ebrahimpoor Z, Asadi M, Azarbayjani MA. Mechanisms of beneficial effects of exercise training on non-alcoholic fatty liver disease (NAFLD): Roles of oxidative stress and inflammation. European Journal of Sport Science 2019; 19 (7): 994-1003.
Hajighasem A, Farzanegi P, Mazaheri Z, Naghizadeh M, Salehi Gh. Effects of resveratrol, exercises and their combination on Farnesoid X receptor, Liver X receptor and Sirtuin 1 gene expression and apoptosis in the liver of elderly rats with nonalcoholic fatty liver. Peer J 2018; 6:5522: 1-15.
Hashemvarzi SA, Heidarianpour A, Fallah Mohammadi Z, Pourghasem M. Synergistic Effects of Aerobic Exercise after Bone Marrow Stem Cell Transplantation on Recovery of Dopaminergic Neurons and Angiogenesis Markers of Parkinsonian Rats. International Journal of Applied Exercise Physiology, 2016, 1 (5):69-80.
Kang R, Zhou Y, Tan S, Zhou G, Aagaard L, Xie L, Bünger C, Bolund L, Luo Y. Mesenchymal stem cells derived from human induced pluripotent stem cells retain adequate osteogenicity and chondrogenicity but less adipogenicity. Stem Cell Research & Therapy (2015) 6:144. 1-14.
Kate Hallsworth, Christian Thoma, Sarah Moore, Thomas Ploetz, Quentin M Anstee, Roy Taylor, Christopher P Day, Michael I Trenell. Non-alcoholic fatty liver disease is associated with higher levels of objectively measured sedentary behaviour and lower levels of physical activity than matched healthy controls. Frontline Gastroenterology 2015; 6:44–51.
Loomba R, Friedman SL, Shulman GI. Mechanisms and disease consequences of nonalcoholic fatty liver disease. Cell 2021;184(10):2537–64.
Muaz Belviranli, Nilsel Okudan, Serkan Revan, Serdar Balci, and Hakki Gokbel. Repeated Supramaximal Exercise-Induced Oxidative Stress: Effect of β-Alanine Plus Creatine Supplementation. Asian J Sports Med. 2016; 7(1): e26843.
Nabizadeh Haghighi A, Shabani R. Comparing effects of medication therapy and exercise training with diet on liver enzymes levels and liver sonography in patients with non-alcoholic fatty liver disease (NAFLD). Journal of University of Medical Sciences 2016; 5(4):488-500.
Norouzpour M, Marandi M, Ghanbarzadeh M, Zare Mayavan A. The effect of com¬bined training on serum concentrations of inflammatory cytokines and factors associated with metabolic syndrome in elderly women with fatty liver. Journal of Sport and Exercise Physiology 2022;15(2):64-75 (Persian).
Pafili K, Roden M. Nonalcoholic fatty liver disease (NAFLD) from pathogenesis to treatment concepts in humans. Mol Metab 2021;50:101122.
Polgar S, Karimi L, Buultjens M, Morris M, Busse M. Assessing the Efficacy of Cell Transplantation for Parkinson’s Disease: A Patient-Centered Approach. Journal of Parkinson's Disease, 2018; 8(3): 375-383.
Pourheydar B , Shahi M, Farjah GH, Javanmard M, Karimipour M, Atabaki F. Evaluation of apoptosis in hippocampal cells of rat following intravenous injection of bone marrow stromal cells in ischemia-reperfusion model. Studies in Medical Sciences 2014, 25(7): 586-597.
Shahriari Felordi M, Torabi Sh, Shokoohian B, Farzaneh Z, Mohamadnejad M, Malekzadeh R, Baharvand H, Vosough M. Novel Cell-Based Therapies in Hepatic Disorders. J Mazandaran Univ Med Sci 2020; 30(185): 184-208 (Persian).
Shamsoddini A, Sobhani V, Ghamar Chehreh ME, Alavian SM, Zaree A. Effect of Aerobic and Resistance Exercise Training on Liver Enzymes and Hepatic Fat in Iranian Men With Nonalcoholic Fatty Liver Disease. Hepat Mon 2015; 15(10):e31434.
Shira Zelber-Sagi, Justyna Godos and Federico Salomone. Lifestyle changes for the treatment of nonalcoholic fatty liver disease: a review of observational studies and intervention trials. Therapeutic Advances in Gastroenterolog 2016; 9(3) 392–407.
Sies H. Oxidative stress: a concept in redox biology and medicine. Redox biology. 2015;4:180-3.
Wahl P, Brixius K, Bloch W. Exercise-induced stem cell activation and its implication for cardiovascular and skeletal muscle regeneration. Minimally Invasive Therapy & Allied Technologies 2022; 17(2): 91-99.
Youkun Bi, Xuejun Guo, Mengqi Zhang, Keqi Zhu, Chentao Sh, Baoqi Fan, Yanyun Wu, Zhiguang Yang and Guangju Ji. Bone marrow derived‑mesenchymal stem cell improves diabetes‑associated fatty liver via mitochondria transformation in mice. Stem Cell Research & Therapy (2021): 12:602.
Zhong Z, Chen A, Fa Z, Ding Z, Xiao L, Wu G, Wang Q, Zhang R. Bone marrow mesenchymal stem cells upregulate PI3K/AKT pathway and down-regulate NF-κB pathway by secreting glial\ cell-derived neurotrophic factors to regulate microglial polarization and alleviate deafferentation pain in rat. Neurobiology of Disease 2020; (143); 1-17.