Influence of N-Acetylcysteine on Movement Activity of Hemipar-kinsonian Rats Induced by Dopamine Receptor Agonist Injection

Authors

  • Iryna Mishchenko Lesya Ukrainka Eastern European National University
  • Olena Mankivska Bogomoletz Institute of Physiology
  • Bohdan Kopyak Bogomoletz Institute of Physiology
  • Nataliya Pil’kevych Bogomoletz Institute of Physiology
  • Oleksandr Motuziuk Lesya Ukrainka Eastern European National University https://orcid.org/0000-0002-1520-0721

DOI:

https://doi.org/10.29038/2617-4723-2019-387-173-178

Keywords:

N-acetylcysteine, antioxidant, hemiparkinsonism, muscular activity, muscle fatigue

Abstract

The muscle contraction during labor activity is accompanied by motor and postural disorders as a results of their fatigue or chronic pain. It is known, that in the process of muscle fatigue development the metabolism is disturbed, products of incomplete oxidation of oxygen – peroxide, free radicals, oxygen ions – are formed. The cells protection from such damage is provided by the antioxidant system. In the field of sport physiology, in the study of muscle fatigue, exogenous antioxidant such as N-acetylcysteine (NAC) is widely used, which accelerates the muscles recovery process after their fatigue. The aim of this study was to detect the preventive effect of a previous injection of NAC on the development of muscle fatigue in a non-anesthetized animal with experimental hemiparkinsonism during prolonged circulatory movements induced by the injection of apomorphine (AM).
The studies were conducted on the Wistar-Kyoto line rats, which caused a one-sided destruction of the dopaminergic (DA) upright system of the brain by injection of 8 μg 6-hydroxidophan dissolved in 4 μl of physiological solution with the addition of 0,1 % of ascorbic acid, which inhibits the oxidation of neurotoxin.
Animals behavioral reactions to the dopaminomimetics injection were an indirect test for the DA-neurons degeneration level in the middle brain. After seven days of 6-hydroxidophanum administration, the animals were divided into the groups: 1 control animals, which caused intense circulatory movements by injection of apomorphine (0,5 mg / kg) (n = 6); 2–rats, which were injected 0.5 ml of physiological solution (n = 6) one hour prior to the injection of AM; 3–animals that were injected with an N-acetylcysteine solution (150 mg / kg) (n = 6) an hour before the injection of AM.
By comparing behavioral tests in rats in three groups, it can be assumed that the decrease in the number of rotation in the control group rats and the animals with the prior injection of the physiological solution was not due to the finish of the apomorphine action, but due to the development of muscle fatigue during prolonged circulatory movements. At the same time, in the rats of the third group, after the application of NAC, there was no decrease in the average number of rotation. This may indicate the activation of the antioxidant defense activity in response to prolonged muscular activity, and the NAC can be considered as a powerful activator of protective mechanisms which reduce the fatigue of skeletal muscle.

References

1. Ervilha, U. F.; Farina, D.; Arendt-Nielsen, L.; Graven-Nielsen T. Experimental muscle pain changes motor control strategies in dynamic contractions. Exp Brain Res, 2005; 164, 215–224 https://doi.org/10.1007/s00221-005-2244-7
2. Gandevia, S. C.; Spinal and supraspinal factors in human muscle fatigue. Physiol Rev; 2001, 8, 1725–1789 https://doi.org/10.1152/physrev.2001.81.4.1725
3. Pinheiro, C. H. J.; Vitzel, K. F.; Curi, R. Effect of N-acetylcysteine on markers of skeletal muscle injury after fatiguing contractile activity. Scand J Med Sci Sports; 2012, 22, 24–33 https://doi.org/10.1111/j.1600-0838.2010.01143.x
4. Powers, S. K.; Jackson, M. J. Exercise-induced oxidative stress: cellular mechanisms and impact on muscle force production. Physiol Rev; 2008, 88, 1243–1276 https://dx.doi.org/10.1152%2Fphysrev.00031.2007
5. Banerjee, A. K.; Mandal, A.; Chanda, D.; Chakraborti, S. Oxidant, antioxidant and physical exercise. Mol Cell Biochem; 2003, 253, 307–312.
6. Boyas, S.; Gueґvel, A. Neuromuscular fatigue in healthy muscle: Underlying factors and adaptation mechanisms. Ann Phys Rehabil Med; 2011, 54, 88–108 https://doi.org/10.1016/j.rehab.2011.01.001
7. Reid, M. B.; Stokić, D. S.; Koch, S. M.; Khawli F. A.; Leis, A. A. N-acetylcysteine inhibits muscle fatigue in humans. J Clin Invest; 1994, 94, 2468–2474 https://doi.org/10.1172/JCI117615
8. Harris, R. C.; Sale C. Beta-alanine supplementation in high-intensity exercise. Med Sport Sci; 2012, 59, 1–17 https://doi.org/10.1159/000342372
9. Gharbi, N.; Pressac, M.; Hadchouel, M.; Szwarc, H.; Wilson, S. R.; Moussa F. C60 fullerene is a powerful antioxidant in vivo with no acute or subacute toxicity. Nano Lett; 2005, 5, 2578–2585. https://doi.org/10.1021/nl051866b
10. Prylutskyy, Y. I.; Vereshchaka, I. V.; Maznychenko, A. V.; Bulgakova, N. V.; Gonchar, O. O.; Kyzyma, O. A.; Ritter, U.; Scharff, P.; Tomiak, T.; Nozdrenko, D. M.; Mishchenko, I. V.; Kostyukov, A. I. C60 fullerene as promising therapeutic agent for correcting and preventing skeletal muscle fatigue. J Nanobiotechnology; 2017, 15(1), 8 https://doi.org/10.1186/s12951-016-0246-1
11. Vereshchaka, I.V.; Bulgakova, N. V.; Mazny-chenko, A. V.; Gonchar, O. O.; Prylutskyy, Y. I.; Ritter, U.; Moska, W.; Tomiak, T.; Nozdrenko, D. M.; Mishchenko, I. V.; Kostyukov, A. I. C60 Fullerenes diminish muscle fatigue in rats comparable to N-acetylcysteine or в-alanine. Front Physiol, 2018, 9, 517 https://doi.org/10.3389/fphys.2018.00517
12. Maisky, V. A.; Oleshko, N. N.; Bazilyuk, O. V.; Talanov, S. A.; Sagach, V. F.; Appenzeller, O. Fos and nitric oxide synthase in rat brain with chronic mesostriatal dopamine deficiency: effects of nitroglycerin and hypoxia. Parkinsonism Relat Disord; 2002, 8:261–270 https://doi.org/10.1016/s1353-8020(01)00030-x
13. Talanov, S. A.; Maisky, V. A.; Fedorenko, O. A. Natural complexes are more effective in neuroprotection than single antioxidants. Neuromedicine; 2017, 1:1–8 http://www.isaacpub.org /23/1458/1/1/11/2018/NRM.html
14. Paxinos, G., Watson, C. The rat brain in stereotaxic coordinates, 3rd edition. Academic Press; 1997.
15. Kirik, D.; Rosenblad, C.; Bjцrklund, A. Characterization of behavioral and neurodegenerative changes following partial lesions of the nigrostriatal dopamine system induced by intrastriatal 6-hyd-roxydopamine in the rat. Exp Neurol; 1998,152, 259–277 https://doi.org/10.1006/exnr.1998.6848
16. Casey, D. P.; Joyner, M. J. Local control of skeletal muscle blood flow during exercise: influence of available oxygen. J Appl Physiol; 2011, 111, 1527–1538 https://doi.org/10.1152/japplphysiol.00895.2011
17. Clanton, T. L.; Zuo, L.; Klawitter P. Oxidants and skeletal muscle function: physiologic and pathophysiologic implications. Proc Soc Exp Biol Med; 1999, 222, 253–262 https://doi.org/10.1046/j.1525-1373.1999.d01-142.x
18. Lee, K. P.; Shin, Y. J.; Cho, S. C.; Lee, S. M.; Bahn, Y. J.; Kim, J. Y.; Kwon, E. S.; Jeong, D. Y.; Park, S. C.; Rhee, S. G.; Woo, H. A.; Kwon, K. S. Peroxiredoxin 3 has a crucial role in the contractile function of skeletal muscle by regulating mitochondrial homeostasis. Free Radical Biol Med; 2014, 77, 298–306 https://doi.org/10.1016/j.freeradbiomed.2014.09.010
19. Clarkson, P. M.; Thompson, H. S. Antioxidants: what role do they play in physical activity and health? Am J Clin Nutr; 2000, 72, 637–646 https://doi.org/10.1093/ajcn/72.2.637S
20. Ferreira, L. F.; Reid, M. B. Muscle-derived ROS and thiol regulation in muscle fatigue. J Appl Physiol; 2008, 104, 853–860 https://doi.org/ 10.1152/japplphysiol.00953.2007
21. Mach, J.; Midgley, A. W.; Dank, S.; Grant, R.; Bentley, D. J. The effect of antioxidant supple-mentation on fatigue during exercise: potential role for NAD+(H). Nutrients; 2010, 2, 319–329 https:// dx.doi.org/10.3390%2Fnu2030319
22. Hong, S. S.; Lee, J. Y.; Lee, J. S.; Lee, H. W.; Kim, H. G.; Lee, S. K.; Park, B. K.; Son, C. G. The traditional drug Gongjin-Dan ameliorates chronic fatigue in a forced-stress mouse exercise model. J Ethnopharmacol; 2015, 168, 268–278. https://doi.org/10.1016/j.jep.2015.04.001

Published

2019-08-27

How to Cite

Influence of N-Acetylcysteine on Movement Activity of Hemipar-kinsonian Rats Induced by Dopamine Receptor Agonist Injection. (2019). Notes in Current Biology, 3(387), 173-178. https://doi.org/10.29038/2617-4723-2019-387-173-178