The effect of a lithium-containing composition on ethanol-induced changes in liver and brain within the experiments on mice
Author Affiliations1Research Institute of Clinical and Experimental Lymphology, 630117, Novosibirsk, Timakov str., 2
2Scientific Institute of Clinical and Experimental Lymphology, 630117, Novosibirsk, Timakov str., 2
3N.N. Vorozhtsov Institute of Organic Chemistry of SB RAS, 630090, Novosibirsk, Academik Lavrentyev av., 9
4Research Institute of Clinical and Experimental Lymphology, 630117, Novosibirsk, Timakov str., 2
5Scientific Institute of Clinical and Experimental Lymphology, 630117, Novosibirsk, Timakov str., 2
Abstract
The work is aimed to assess the effect of lithium-containing composition on pathogenic pathway in liver and brain based on model of chronic alcohol abuse. Materials and methods. During the work we used nonlinear mice – males, weighing 25–30 g. For studies mice were randomly assigned to groups: first group was intact animals, mice from second and third groups received 40 % ethanol solution (3 g per 1 kg body weight) along with 5 % ethanol solution as a free drinking every day for 5 weeks; in addition starting from the third week of the experiment mice from the third group were administered suspension lithium-containing composition intragastrically. Starting from the third week of the experiment organs and blood samplings were taken every seven days for analysis. Results and discussion. Based on biochemical and histological analysis we determined that after lithium-containing composition administration it was observed reduction perineural and perivascular edemas in brain, reduction of total content of hyperchromic neurons and intercellular space reduction in liver among mice from the third intervention group in comparison with another negative control group. Proposed drug dosage form of lithium has a comprehensive protection effect on neurons and hepatic cells, it shows antitoxic property in case of chronic alcohol abuse.
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References
- Batukhtina E. I. Psycho - neuroimmunological laws of formation of psychoactive substance dependence: abstract of thesis…doctor of medical sciences. Tomsk, 2014. [In Russian]
- Bochkov V.N., Dobrovolsky A.B., Kushlinsky N.E. et al. Clinical biochemistry: Textbook. / Ed. V.A. Tkachuk. 3rd ed., Rev. and add. М.: GEOTAR-MED, 2008. - 264 p. [In Russian]
- Golovenko N. Ya., Zhuk M. S., Zinkovskij V. G., Zhuk O. V., Kopanica M. V. Pharmacokinetics of ethanol in mice with different alcohol motivation // Byul. ehksper. biologii i mediciny. 2001, vol. 132, no. 9, pp. 281-284. [In Russian]
- Zamoschina T.A. 35 years of study of lithium salts // Bulletin of siberian medicine. 2006. (5) 26-29. [In Russian]
- Ishchenko I.Yu, Michurina S.V. The impact of the sorbent "Enterosgel" in the textile districts of the liver and regional lymph nodes in rats with chronic toxic hepatitis. // Bulletin SB RAMN.- 2006.- N1.- S.67-72. [In Russian]
- Lapin A.A. Clinical - morphological criteria for the diagnosis of alcoholism: abstract of thesis…doctor of medical sciences. Volgograd, 2007. [In Russian]
- Lapin A.A., Lapina A.A. Morphological and histochemical characterization of the vascular plexus of the brain in acute and chronic alcohol intoxication in experiment // Natural sciences: journal of basic and applied research. - Astrakhan: The publishing house "Astrakhan University», 2006. - №3 (12). - 27-29. [In Russian]
- Manskikh V.N. Pathology laboratory mouse liver: the pitfalls on the way to the correct diagnosis / The electronic document /http://ruslasa.ru/wp-content/uploads/Patologiya-pecheni-metodichka-dlya-sayta.pdf. [In Russian]
- Mashkovskij M. D. Lekarstvennye sredstva [Drugs]. Moscow, Novaya Volna Publ., 2005. 1216 p. [In Russian]
- Fedorov V. P., Afanasiev R.V., Sgibneva N.V., Maslov N.V. Morphofunctional state neurocytes of the brain with increased radiation background //Morphology. – 2010. – V. 137, № 4. – Pg. 200. [In Russian]
- Bertola A., Mathews S., Sung Hwan Ki, Hua Wang, Bin Ga. Mouse model of chronic and binge ethanol feeding (the NIAAA model) // Nat. Protoc. 2013. Mar. V. 8, №3. P. 627–637. doi:10.1038/nprot.2013.032. doi: 10.1038/nprot.2013.032.
- Chakrabortya G., Saitob M., Maoa R.-F., Wanga R., Vadasza C., Saitoa M. Lithium blocks ethanol-induced modulation of protein kinases in the developing brain // Bioch. Biophys. Res. Commun. 2008. Vol. 367. Р. 597–602.
- Chandler L. J., Sutton G. Acute ethanol inhibits extracellular signal-regulated kinase, protein kinase B, and adenosine 3':5'-cyclic monophosphate response element binding protein activity in an age- and brain region-specific manner // Alcohol. Clin. Exp. Res. 2005. Vol. 29. Р. 672–680.
- Chi-Tso Chiu, De-Maw Chuang. Molecular actions and therapeutic potential of lithium in preclinical and clinical studies of CNS disorders // Pharmacol. Ther. 2010. Vol. 128, № 2. Р. 281–304.
- Chuang D. M. Neuroprotective and neurotrophic actions of the mood stabilizer lithium: can it be used to treat neurodegenerative diseases? // Crit. Rev. Neurobiol. 2004. Vol. 16. Р. 83–90.
- Chuang D. M., Chen R. W., Chalecka-Franaszek E., Ren M., Hashimoto R., Senatorov V., Kanai H., Hough C., Hiroi T., Leeds P. Neuroprotective effects of lithium in cultured cells and animal models of diseases // Bipolar. Disord. 2002. Vol. 4. Р. 129–136.
- Einat H., Yuan P., Gould T. D., Li J., Du J., Zhang L., Manji H. K., Chen G. The role of the extracellular signal-regulated kinase signaling pathway in mood modulation // J. Neurosci. 2003. Vol. 23. Р. 7311–7316.
- Hashimoto R, Takei N, Shimazu K, Christ L, Lu B, Chuang DM. Lithium induces brain-derived neurotrophic factor and activates TrkB in rodent cortical neurons: an essential step for neuroprotection against glutamate excitotoxicity. Neuropharmacology 2002 Dec;43(7):1173-9.
- Muresanu D. F Neuroprotection and neuroplasticity - a holistic approach and future perspectives// J Neurol Sci. 2007 Jun 15;257(1-2):38-43.
- Noble W., Planel E., Zehr C., Olm V., Meyerson J., Suleman F., Gaynor K., Wang L., LaFrancois J., Feinstein B., Burns M., Krishnamurthy P., Wen Y., Bhat R., Lewis J., Dickson D., Duff K. Inhibition of glycogen synthase kinase-3 by lithium correlates with reduced tauopathy and degeneration in vivo // Proc. Natl. Acad. Sci. USA. 2005. Vol. 102. Р. 6990–6995.
- Tabakoff B., Hoffman PL. Animal models in alcohol research // Alcohol Res Health, 2000. V. 24, №2. P. 77-84.
- Young C., Straiko M. M. W., Johnson S. A., Creeley C., Olney J. W. Ethanol causes and lithium prevents neuroapoptosis and suppression of pERK in the infant mouse brain // Neurobiol. Dis. 2008. Vol. 31. Р. 355–360.
- Zhu ZF, Wang QG, Han BJ, William CP. Neuroprotective effect and cognitive outcome of chronic lithium on traumatic brain injury in mice. Brain Res Bull 2010 Oct 30;83 (5):272-7.
About Authors (Correspondence):
Kotlyarova A.A. – postgraduate student, junior researcher of the laboratory of lymphoregulation, e-mai: kotlyarova.anastasiya@yandex.ru
Letyagin A.Yu. – doctor of medical sciences, leading researcher of the laboratory of lymphoregulation, professor, e-mail: letyagin-andrey@yandex.ru
Tolstikova T.G. – doctor of biological sciences, head of the laboratory of pharmacological investigation, professor
Bgatova N.P. – doctor of biological sciences, head of the laboratory ultrastructural researches, professor, e-mai: n_bgatova@ngs.ru
Rachkovskaya L.N. – candidate of chemical sciences, head of the laboratory of lymphoregulation, e-mai: noolit@niikel.ru
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