ABSTRACT
Objectives:
To investigate the results of exhaustive exercise on hepatocyte hyperplasia in an animal experiment consisting of partial hepatectomy.
Materials and Methods:
The experimental study was conducted with 24 Wistar Albino rats weighing between 225 and 275. Whereas exhaustive exercise was performed twice after 70% hepatectomy in the experimental group (n=12); the control group (n=12) did not perform an exercise. Then, rats underwent total hepatectomy 72 hours after partial hepatectomy. Groups were compared in terms of regeneration index, regenerative changes in hepatocytes, mitosis, and Ki-67 staining levels.
Results:
The groups were similar at baseline (at the time of 70% liver resection) regarding regenerative changes, mitosis count, and Ki-67. Regeneration index after exercise were 2.02±0.40 in the experimental group; and 2.42±0.21 in the control group (p=0.007). There was no difference between the groups in terms of regenerative scores (p=0.842) and Ki-67 staining (p=0.200) measured after total hepatectomy. However, mitosis was lower in the experimental group than the control group (11.5 vs. 26.0; p=0.010).
Conclusion:
It was showed that effect of exhaustive exercise on liver regeneration is negative according to mitosis count and liver mass increase but did not affect histologic changes of regeneration and Ki-67 staining. Blood tests and detailed immunohistochemical studies may reveal mechanisms of effect of exercise on liver cell hyperplasia and its potential clinical benefits.
Keywords:
Exercise, Liver, Regeneration
References
1Taub R. Liver regeneration: from myth to mechanism. Nat Rev Mol Cell Biol. 2004;5:836-847.
2Preziosi ME, Monga SP. Update on the Mechanisms of Liver Regeneration. Semin Liver Dis. 2017;37:141-151.
3Wang FS, Fan JG, Zhang Z, et al. The global burden of liver disease: the major impact of China. Hepatology. 2014;60:2099-2108.
4Koniaris LG, McKillop IH, Schwartz SI, et al. Liver regeneration. J Am Coll Surg. 2003;197:634-659.
5Fausto N, Campbell JS, Riehle KJ. Liver regeneration. Hepatology. 2006;43:45-53.
6Mastellos DC, Deangelis RA, Lambris JD. Inducing and characterizing liver regeneration in mice: Reliable models, essential “readouts” and critical perspectives. Curr Protoc Mouse Biol. 2013;3:141-170.
7Andersen KJ, Knudsen AR, Kannerup AS, et al. The natural history of liver regeneration in rats: description of an animal model for liver regeneration studies. Int J Surg. 2013;11:903-908.
8Higgins GM, Anderson RM, Higgins G, et al. Experimental pathology of the liver: Restoration of the liver of the white rat following partial surgical removal. AMA Arch pathol. 1931;12:186-202.
9Gandra PG, Valente RH, Perales J, et al. Proteomic analysis of rat skeletal muscle submitted to one bout of incremental exercise. Scand J Med Sci Sports. 2012;22:207-216.
10Sasanuma H, Mortensen FV, Knudsen AR, et al. Increased liver regeneration rate and decreased liver function after synchronous liver and colon resection in rats. Ann Surg Innov Res. 2009;3:16.
11Marshak A, Walker AC. MITOSIS IN REGENERATING LIVER. Science. 1945;101:94-95.
12Tannuri AC, Tannuri U, Coelho MC, et al. Experimental models of hepatectomy and liver regeneration using newborn and weaning rats. Clinics (Sao Paulo). 2007;62:757-762.
13Gerlach C, Sakkab DY, Scholzen T, et al. Ki-67 expression during rat liver regeneration after partial hepatectomy. Hepatology. 1997;26:573-578.
14Marongiu F, Marongiu M, Contini A, et al. Hyperplasia vs hypertrophy in tissue regeneration after extensive liver resection. World J Gastroenterol. 2017;23:1764-1770.
15Klaas M, Kangur T, Viil J, et al. The alterations in the extracellular matrix composition guide the repair of damaged liver tissue. Sci Rep. 2016;6:27398.
16Moolten FL, Bucher NL. Regeneration of rat liver: transfer of humoral agent by cross circulation. Science. 1967;158:272-274.
17 van der Windt DJ, Sud V, Zhang H, et al. The Effects of Physical Exercise on Fatty Liver Disease. Gene Expr. 2018;18:89-101.
18Nieman DC. Current perspective on exercise immunology. Curr Sports Med Rep. 2003;2:239-242.
19Terra R, da Silva SAG, Pinto VS, et al. Effect of exercise on immune system: response, adaptation and cell signaling. Rev Bras Med Esporte. 2012;18:208-214.
20Pedersen BK, Febbraio MA. Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol Rev. 2008;88:1379-1406.
21Pedersen BK, Fischer CP. Physiological roles of muscle-derived interleukin-6 in response to exercise. Curr Opin Clin Nutr Metab Care. 2007;10:265-271.
22Nieman DC, Davis JM, Henson DA, et al. Carbohydrate ingestion influences skeletal muscle cytokine mRNA and plasma cytokine levels after a 3-h run. J Appl Physiol (1985). 2003;94:1917-1925.
23Czarkowska-Paczek B, Bartlomiejczyk I, Przybylski J. The serum levels of growth factors: PDGF, TGF-beta and VEGF are increased after strenuous physical exercise. J Physiol Pharmacol. 2006;57:189-197.
24Rowsey PJ, Metzger BL, Carlson J, et al. Long-term exercise training selectively alters serum cytokines involved in fever. Biol Res Nurs. 2009;10:374-380.
25Radák Z, Asano K, Inoue M, et al. Superoxide dismutase derivative prevents oxidative damage in liver and kidney of rats induced by exhausting exercise. Eur J Appl Physiol Occup Physiol. 1996;72:189-194.
26Linecker M, Frick L, Kron P, et al. Exercise Improves Outcomes of Surgery on Fatty Liver in Mice: A Novel Effect Mediated by the AMPK Pathway. Ann Surg. 2020;271:347-355.
