Journal of Kerman University of Medical Sciences

Concomitant L-carnitine supplementation and exercise training affects apoptosis in male rats

Document Type : Original Article

Authors

Beydolah Shahouzehi 1, 2
Banafsheh Daneshmand 3
Mahdieh Nazari-Robati 4
Soheil Aminizadeh 5
Yaser Masoumi-Ardakani 6

1 Student Research Committee, Kerman University of Medical Science, Kerman, Iran

2 Gastroenterology and Hepatology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

3 Department of Physiology (Sport Science), Central Tehran Branch, Islamic Azad University, Tehran, Iran

4 Department of Clinical Biochemistry, Faculty of Medicine, Kerman University of Medical Sciences, Kerman, Iran

5 Department of Physiology and Pharmacology, Afzalipour School of Medicine, and Physiology Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

6 Physiology Research Center, Institute of Basic and Clinical Physiology Sciences, Kerman University of Medical Sciences, Kerman, Iran

https://doi.org/10.34172/jkmu.2024.47
Abstract
Background: Apoptosis is a defensive measure that removes dysfunctional cells. Exercise training has a broad spectrum of benefits that influence apoptosis and cell viability. L-carnitine (LCAR), a supplement nowadays, has shown beneficial effects against cell death. We investigated the simultaneous effect of exercise training (acute exercise [AE] and high-intensity interval training [HIIT]) and LCAR supplementation on the proteins involved in apoptosis. The animals were anesthetized twenty-four hours after the conclusion of the final training session.
Methods: Forty-eight male Wistar rats (210±10 g) were assigned to six groups (n=8) as follows: Control, LCAR (200 mg/kg/d LCAR, IP), AE, HIIT, LCAR+AE, and LCAR+HIIT. The animals were anesthetized and sacrificed twenty-four hours after the last training session; the rats’ blood sample was collected, and the serum was separated. The serum Bcl-2 levels, as an anti-apoptotic factor, and caspase-3 and BAX, as proapoptotic factors, were measured using specific ELISA kits.
Results: AE increased apoptosis, but HIIT’s effects were almost neutral. LCAR administration in groups that performed either AE or HIIT significantly attenuated apoptosis. However, in group 6 (LCAR+HIIT), the anti-apoptotic effects were noteworthy because LCAR+HIIT significantly increased Bcl-2 and reduced caspase-3 levels compared to the control group.
Conclusion: HIIT improved cell viability through increasing Bcl-2 levels, and LCAR strengthened HIIT’s anti-apoptotic properties. AE increased proapoptotic proteins, and LCAR modified the elevated proapoptotic markers in the AE group. Therefore, LCAR may be considered a promising supplement against exercise-mediated injury. This study can be extended to humans to evaluate the beneficial effects of LCAR+HIIT and LCAR+AE.

Keywords

L-carnitine
Apoptosis
Bcl-2
Exercise
Subjects
  1. Modanloo M, Shokrzadeh M. Analyzing mitochondrial dysfunction, oxidative stress, and apoptosis: potential role of L-carnitine. Iran J Kidney Dis. 2019;13(2):74-86.
  2. Vieira H, Kroemer G. Mitochondria as targets of apoptosis regulation by nitric oxide. IUBMB Life. 2003;55(10-11):613- 6. doi: 10.1080/15216540310001639652.
  3. Chandhok G, Lazarou M, Neumann B. Structure, function, and regulation of mitofusin-2 in health and disease. Biol Rev Camb Philos Soc. 2018;93(2):933-49. doi: 10.1111/ brv.12378.
  4. Shahouzehi B, Masoumi-Ardakani Y, Fallah H, Aminizadeh S. Concomitant administration of L-carnitine and performing highintensity interval training effects on the genes involved in mitochondrial fusion and apoptosis in rat liver. Jordan J Biol Sci. 2023;16(1):21-6. doi: 10.54319/jjbs/160104.
  5. Pourrazi H, Asgharpour-Arshad M, Gholami F, Abbasi S. Effect of high-intensity interval training on apoptotic gene expression in rat myocardial tissue. Gene Cell Tissue. 2020;7(2):e101963. doi: 10.5812/gct.101963.
  6. Holloway TM, Bloemberg D, da Silva ML, Simpson JA, Quadrilatero J, Spriet LL. High intensity interval and endurance training have opposing effects on markers of heart failure and cardiac remodeling in hypertensive rats. PLoS One. 2015;10(3):e0121138. doi: 10.1371/journal.pone.0121138.
  7. Nami R, Mondillo S, Agricola E, Lenti S, Ferro G, Nami N, et al. Aerobic exercise training fails to reduce blood pressure in nondipper-type hypertension. Am J Hypertens. 2000;13(6 Pt 1):593-600. doi: 10.1016/s0895-7061(99)00265-4.
  8. Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004;18(10):1150-2. doi: 10.1096/fj.03-1291fje.
  9. González A, Fortuño MA, Querejeta R, Ravassa S, López B, López N, et al. Cardiomyocyte apoptosis in hypertensive cardiomyopathy. Cardiovasc Res. 2003;59(3):549-62. doi: 10.1016/s0008-6363(03)00498-x.
  10. Kwak HB. Effects of aging and exercise training on apoptosis in the heart. J Exerc Rehabil. 2013;9(2):212-9. doi: 10.12965/ jer.130002.
  11. Holloszy JO, Coyle EF. Adaptations of skeletal muscle to endurance exercise and their metabolic consequences. J Appl Physiol Respir Environ Exerc Physiol. 1984;56(4):831-8. doi: 10.1152/jappl.1984.56.4.831.
  12. Moradi A, Hosseini SA, Nikbakht M. Anti-apoptotic effects of interval and continued training and crocin on the muscle tissue of the rats with type II diabetes induced by a high-fat diet. J Nutr Fasting Health. 2019;7(3):130-7. doi: 10.22038/ jnfh.2019.39346.1186.
  13. Moradian F, Nazarali P, Alizadeh R. The effect of eight weeks of endurance and resistance training on apoptotic indexes in young men. J Isfahan Med Sch. 2018;36(489):845-52. doi: 10.22122/jims.v36i489.10268.
  14. Cha YS. Effects of L-carnitine on obesity, diabetes, and as an ergogenic aid. Asia Pac J Clin Nutr. 2008;17 Suppl 1:306-8.
  15. Masoumi-Ardakani Y, Aminizadeh S, Fallah H, Shahouzehi B. L-carnitine different doses affect serum and pancreas tissue Antioxidative defense and histopathology in STZ-induced diabetic rats. Biologia. 2020;75(9):1415-23. doi: 10.2478/ s11756-020-00432-y.
  16. Shahouzehi B, Masoumi-Ardakani Y, Nazari-Robati M, Aminizadeh S. The effect of high-intensity interval training and L-carnitine on the expression of genes involved in lipid and glucose metabolism in the liver of Wistar rats. Braz Arch Biol Technol. 2022;66:e23220100. doi: 10.1590/1678-4324- 2023220100.
  17. Carnevali LC Jr, Eder R, Lira FS, Lima WP, Gonçalves DC, Zanchi NE, et al. Effects of high-intensity intermittent training on carnitine palmitoyl transferase activity in the gastrocnemius muscle of rats. Braz J Med Biol Res. 2012;45(8):777-83. doi: 10.1590/s0100-879x2012007500105.
  18. Holloway TM, Bloemberg D, da Silva ML, Quadrilatero J, Spriet LL. High-intensity interval and endurance training are associated with divergent skeletal muscle adaptations in a rodent model of hypertension. Am J Physiol Regul Integr Comp Physiol. 2015;308(11):R927-34. doi: 10.1152/ ajpregu.00048.2015.
  19. Fallahi AA, Shekarfroush S, Rahimi M, Jalali A, Khoshbaten A. Alteration in cardiac uncoupling proteins and eNOS gene expression following high-intensity interval training in favor of increasing mechanical efficiency. Iran J Basic Med Sci. 2016;19(3):258-64.
  20. Phaneuf S, Leeuwenburgh C. Apoptosis and exercise. Med Sci Sports Exerc. 2001;33(3):393-6.
  21. Jabbari E, Gholami M, Nikbakht H, Shakeri N, Ghazaliyan F. Effect of aerobic training and L-carnitine supplementation on some apoptotic factors in diabetic rat liver. Razi J Med Sci. 2019;26(7):131-40.
  22. Verboven M, Cuypers A, Deluyker D, Lambrichts I, Eijnde BO, Hansen D, et al. High intensity training improves cardiac function in healthy rats. Sci Rep. 2019;9(1):5612. doi: 10.1038/s41598-019-42023-1.
  23. Kelek SE, Afşar E, Akçay G, Danışman B, Aslan M. Effect of chronic L-carnitine supplementation on carnitine levels, oxidative stress and apoptotic markers in peripheral organs of adult Wistar rats. Food Chem Toxicol. 2019;134:110851. doi: 10.1016/j.fct.2019.110851.
  24. Vardiyan R, Ezati D, Anvari M, Ghasemi N, Talebi A. Effect of L-carnitine on the expression of the apoptotic genes Bcl-2 and Bax. Clin Exp Reprod Med. 2020;47(3):155-60. doi: 10.5653/ cerm.2019.03440.
  25. Eydivandi K, Azarbayjani MA, Farzanegi P. The effect of high intensity interval training (HIIT) and crocin consumption on doxorubicin-induced apoptotic indices in the muscle tissue of rats. Gene Cell Tissue. 2020;7(4):e108227. doi: 10.5812/ gct.108227.
  26. Delfan M, Delphan M, Kordi MR, Ravasi AA, Safa M, Gorgani-Firuzjaee S, et al. High intensity interval training improves diabetic cardiomyopathy via miR-1 dependent suppression of cardiomyocyte apoptosis in diabetic rats. J Diabetes Metab Disord. 2020;19(1):145-52. doi: 10.1007/s40200-019-00485-0.
  27. Hoene M, Lehmann R, Hennige AM, Pohl AK, Häring HU, Schleicher ED, et al. Acute regulation of metabolic genes and insulin receptor substrates in the liver of mice by one single bout of treadmill exercise. J Physiol. 2009;587(1):241-52. doi: 10.1113/jphysiol.2008.160275.
  28. Kim KH, Kim SH, Min YK, Yang HM, Lee JB, Lee MS. Acute exercise induces FGF21 expression in mice and in healthy humans. PLoS One. 2013;8(5):e63517. doi: 10.1371/journal. pone.0063517.
  29. Alihemmati A, Ebadi F, Moghadaszadeh M, Asadi M, Zare P, Badalzadeh R. Effects of high-intensity interval training on the expression of microRNA-499 and pro- and anti-apoptotic genes in doxorubicin-cardiotoxicity in rats. J Electrocardiol. 2019;55:9-15. doi: 10.1016/j.jelectrocard.2019.02.009.
  30. Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004;18(10):1150-2. doi: 10.1096/fj.03-1291fje.
  31. Yoo SZ, No MH, Heo JW, Chang E, Park DH, Kang JH, et al. Effects of a single bout of exercise on mitochondria-mediated apoptotic signaling in rat cardiac and skeletal muscles. J Exerc Rehabil. 2019;15(4):512-7. doi: 10.12965/jer.1938380.190.
  32. Asadikaram G, Ram M, Izadi A, Sheikh Fathollahi M, Nematollahi MH, Najafipour H, et al. The study of the serum level of IL-4, TGF-β, IFN-γ, and IL-6 in overweight patients with and without diabetes mellitus and hypertension. J Cell Biochem. 2019;120(3):4147-57. doi: 10.1002/jcb.27700.
  33. Mooren FC, Krüger K. Exercise, autophagy, and apoptosis. Prog Mol Biol Transl Sci. 2015;135:407-22. doi: 10.1016/ bs.pmbts.2015.07.023.
  34. Mohammadi V, Sharifi SD, Sharafi M, Mohammadi- Sangcheshmeh A, Abedheydari E, Alizadeh A. Dietary L-carnitine affects the expression of genes involved in apoptosis and fatty acid metabolism in rooster testes. Andrologia. 2020;52(11):e13876. doi: 10.1111/and.13876.
Journal of Kerman University of Medical Sciences
Volume 31, Issue 6
November and December 2024
Pages 305-311

Home

Editorial Board

Guide for Authors

Submit Manuscript

Guide for Reviewers

Contact Us