vestimИзвестия Национальной академии наук Беларуси. Серия медицинских наукProceedings of the National Academy of Sciences of Belarus, Medical series1814-60232524-2350The Republican Unitary Enterprise Publishing House "Belaruskaya Navuka"10.29235/1814-6023-2019-16-2-244-256vestim-501Research ArticleОБЗОРЫREVIEWSРоль рецепторов, активирующих пролиферацию пероксисом, в контроле алкогольной зависимости и лечении сопутствующих заболеваний печениRole of peroxisome proliferator-activated receptors in the control of alcohol dependence and concomitant liver pathologyСемененяИ. Н.SemenenyaI. N.

Семененя Игорь Николаевич – д-р мед. наук, профессор, директор

Бульвар Ленинского комсомола, 50, 230030, г. Гродно

Igor N. Semenenya – D. Sc. (Med.), Professor, Director

50, BLK, 230030, Grodno

insemenenya@yandex.byШляхтунА. Г.ShlyahtunA. H.

Шляхтун Алексей Генрихович – заведующий лабораторией

Бульвар Ленинского комсомола, 50, 230030, г. Гродно

Alexej H. Shlyahtun – Head of the Laboratory

50, BLK, 230030, Grodno

a.shlyahtun@gmail.comРадутаЕ. Ф.RadutaH. F.

Радута Елена Францевна – ст. науч. сотрудник

Бульвар Ленинского комсомола, 50, 230030, г. Гродно

Helena F. Raduta – Senior researcher

50, BLK, 230030, Grodno

e.raduta@ibiochemistry.byИнститут биохимии биологически активных соединений НАН БеларусиInstitute of Biochemistry of Biologically Active Compounds of the National Academy of Sciences of Belarus201901072019162244256Copyright © Семененя И.Н., Шляхтун А.Г., Радута Е.Ф., 20192019Семененя И.Н., Шляхтун А.Г., Радута Е.Ф.Semenenya I.N., Shlyahtun A.H., Raduta H.F.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://vestimed.belnauka.by/jour/article/view/501

Настоящий обзор посвящен систематизации разрозненных данных о биологической роли рецепторов, активирующих пролиферацию пероксисом (PPARs), и изучению возможности использования агонистов PPARs в лечении пациентов с алкогольной зависимостью и сопутствующими заболеваниями печени. Рассмотрены наиболее важные работы последних лет, раскрывающие терапевтический потенциал агонистов PPARs в качестве средств для лечения пациентов с алкогольной зависимостью.

The article is aimed to summarize the scattered data on the role of peroxisome proliferator-activated receptors (PPAR) and the possibility of using PPAR’s agonists for treatment of alcohol dependence and alcoholic liver disease. Earlier it was shown that some PPAR agonists can reduce ethanol consumption and preference in rodents. Several hypotheses considering the antialcoholic activity of PPAR agonists and the roles of PPAR in the development of alcohol dependence were discussed. In light of these data, the therapeutic potential of PPARs agonists as an agent for the treatment of alcoholism, has been reviewed.

рецепторыактивирующие пролиферацию пероксисом (PPARs)агонисты PPARsалкоголизмалкогольная болезнь печениPeroxisome proliferator-activated receptorPPARalcoholismalcoholic liver diseaseReferencesMiller, P. M. Medical treatment of alcohol dependence: a systematic review / P. M. Miller, S. W. Book, S. H. Stewart // Int. J. Psychiatry Med. – 2011. – Vol. 42, N 3. – P. 227–266. https://doi.org/10.2190/PM.42.3.bMiller P. M., Book S. W., Stewart S. H. Medical treatment of alcohol dependence: a systematic review. International Journal of Psychiatry, 2011, vol. 42, no. 3, pp. 227–266. https://doi.org/10.2190/PM.42.3.bControl of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors / C. Dreyer [et al.] // Cell. – 1992. – Vol. 68, N 5. – P. 879–887. https://doi.org/10.1016/0092-8674(92)90031-7Dreyer C., Krey G., Keller H., Givel F., Helftenbein G., Wahli W. Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell, 1992, vol. 68, no. 5, pp. 879–887. https://doi.org/10.1016/0092-8674(92)90031-7Issemann, I. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators / I. Issemann, S. Green // Nature. – 1990. – Vol. 347, N 6294. – P. 645–650. https://doi.org/10.1038/347645a0Issemann I., Green S. Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature, 1990, vol. 347, no. 6294, pp. 645–650. https://doi.org/10.1038/347645a0Differential expression and activation of a family of murine peroxisome proliferator-activated receptors / S. A. Kliewer [et al.] // Proc. Natl. Acad. Sci. – 1994. – Vol. 91, N 15. – P. 7355–7359. https://doi.org/10.1073/pnas.91.15.7355Kliewer S. A., Forman B. M., Blumberg B., Ong E. S., Borgmeyer U., Mangelsdorf D. J., Umesono K., Evans R. M. Differential expression and activation of a family of murine peroxisome proliferator-activated receptors. Proceedings of the National Academy of Sciences, 1994, vol. 91, no. 15, pp. 7355–7359. https://doi.org/10.1073/pnas.91.15.7355Grygiel-Górniak, B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review / B. Grygiel-Górniak // Nutr. J. – 2014. – Vol. 13. – Art. 17. https://doi.org/10.1186/1475-2891-13-17Grygiel-Górniak B. Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications – a review. Nutrition Journal, 2014, vol. 13, аrt. 17. https://doi.org/10.1186/1475-2891-13-17Regulation of peroxisome proliferator-activated receptor-alpha expression during lung inflammation / J. Becker [et al.] // Pulm. Pharmacol. Ther. – 2008. – Vol. 21, N 2. – P. 324–330. https://doi.org/10.1016/j.pupt.2007.08.001Becker J., Delayre-Orthez C., Frossard N., Pons F. Regulation of peroxisome proliferator-activated receptor-alpha expression during lung inflammation. Pulmonary Pharmacology and Therapeutics, 2008, vol. 21, no. 2, pp. 324–330. https://doi.org/10.1016/j.pupt.2007.08.001Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms / E. Mueller [et al.] // J. Biol. Chem. – 2002. – Vol. 277, N 44. – P. 41925–41930. https://doi.org/10.1074/jbc.M206950200Mueller E., Drori S., Aiyer A., Yie J., Sarraf P., Chen H. [et al.]. Genetic analysis of adipogenesis through peroxisome proliferator-activated receptor gamma isoforms. Journal of Biological Chemistry, 2002, vol. 277, no. 44, pp. 41925–41930. https://doi.org/10.1074/jbc.M206950200Brunmeir, R. Functional regulation of PPARs through post-translational modifcations / R. Brunmeir, F. Xu // Int. J. Mol. Sci. – 2018. – Vol. 19, N 6. – Art. 1738. https://doi.org/10.3390/ijms19061738Brunmeir R., Xu F. Functional regulation of PPARs through post-translational modifcations. International Journal of Molecular Sciences, 2018, vol. 19, no. 6, аrt. 1738. https://doi.org/10.3390/ijms19061738Rochette-Egly, C. Nuclear receptors: integration of multiple signalling pathways through phosphorylation / C. Rochette-Egly // Cell Signal. – 2003. – Vol. 15, N 4. – P. 355–366. https://doi.org/10.1016/S0898-6568(02)00115-8Rochette-Egly C. Nuclear receptors: integration of multiple signalling pathways through phosphorylation. Cellular Signalling, 2003, vol. 15, no. 4, pp. 355–366. https://doi.org/10.1016/S0898-6568(02)00115-8Zoete, V. Peroxisome proliferator-activated receptor structures: ligand specifcity, molecular switch and interactions with regulators / V. Zoete, A. Grosdidier, O. Michielin // Biochim. Biophys. Acta – Mol. Cell Biol. Lipids. – 2007. – Vol. 1771, N 8. – P. 915–925. https://doi.org/10.1016/j.bbalip.2007.01.007Zoete V., Grosdidier A., Michielin O. Peroxisome proliferator-activated receptor structures: ligand specifcity, molecular switch and interactions with regulators. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2007, vol. 1771, no. 8, pp. 915–925. https://doi.org/10.1016/j.bbalip.2007.01.007Sonoda, J. Nuclear receptors: decoding metabolic disease / J. Sonoda, L. Pei, R. M. Evans // FEBS Lett. – 2008. – Vol. 582, N 1. – P. 2–9. https://doi.org/10.1016/j.febslet.2007.11.016Sonoda J., Pei L., Evans R. M. Nuclear receptors: decoding metabolic disease. FEBS Letters, 2008, vol. 582, no. 1, pp. 2–9. https://doi.org/10.1016/j.febslet.2007.11.016Molecular recognition of fatty acids by peroxisome proliferator-activated receptors / H. E. Xu [et al.] // Mol. Cell. – 1999. – Vol. 3, N 3. – P. 397–403. https://doi.org/10.1016/S1097-2765(00)80467-0Xu H. E., Lambert M. H., Montana V. G., Parks D. J., Blanchard S. G., Brown P. J. [et al.]. Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Molecular Cell, 1999, vol. 3, no. 3, pp. 397–403. https://doi.org/10.1016/S1097-2765(00)80467-0Fatty acids, eicosanoids, and hypolipidemic agents identifed as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay / G. Krey [et al.] // Mol. Endocrinol. – 1997. – Vol. 11, N 6. – P. 779–791. https://doi.org/10.1210/mend.11.6.0007Krey G., Braissant O., L’Horset F., Kalkhoven E., Perroud M., Parker M. G., Wahli W. Fatty acids, eicosanoids, and hypolipidemic agents identifed as ligands of peroxisome proliferator-activated receptors by coactivator-dependent receptor ligand assay. Molecular Endocrinology, 1997, vol. 11, no. 6, pp. 779–791. https://doi.org/10.1210/mend.11.6.0007Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1 alpha in human skeletal muscle, but not lipid regulatory genes / M. J. Watt [et al.] // J. Mol. Endocrinol. – 2004. – Vol. 33, N 2. – P. 533–544. https://doi.org/10.1677/jme.1.01499Watt M. J., Southgate R. J., Holmes A. G., Febbraio M. A. Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) alpha and delta and PPAR coactivator 1 alpha in human skeletal muscle, but not lipid regulatory genes. Journal of Molecular Endocrinology, 2004, vol. 33, no. 2, pp. 533–544. https://doi.org/10.1677/jme.1.01499Siersbaek, R. PPARgamma in adipocyte differentiation and metabolism – novel insights from genome-wide studies / R. Siersbaek, R. Nielsen, S. Mandrup // FEBS Lett. – 2010. – Vol. 584, N 15. – P. 3242–3249. https://doi.org/10.1016/j.febslet.2010.06.010Siersbaek R., Nielsen R., Mandrup S. PPARgamma in adipocyte differentiation and metabolism – novel insights from genome-wide studies. FEBS Letters, 2010, vol. 584, no. 15, pp. 3242–3249. https://doi.org/10.1016/j.febslet.2010.06.010Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPARalpha, -beta, and -gamma in the adult rat / O. Braissant [et al.] // Endocrinology. – 1996. – Vol. 137, N 1. – P. 354–366. https://doi.org/10.1210/endo.137.1.8536636.Braissant O., Foufelle F., Scotto C., Dauça M., Wahli W. Differential expression of peroxisome proliferator-activated receptors (PPARs): tissue distribution of PPAR-alpha, -beta, and -gamma in the adult rat. Endocrinology, 1996, vol. 137, no. 1, pp. 354–366. https://doi.org/10.1210/endo.137.1.8536636Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis / P. Lefebvre [et al.] // J. Clin. Invest. – 2006. – Vol. 116, N 3. – P. 571–580. https://doi.org/10.1172/JCI27989Lefebvre P., Chinetti G., Fruchart J.-Ch., Staels B. Sorting out the roles of PPAR alpha in energy metabolism and vascular homeostasis. Journal of Clinical Investigation, 2006, vol. 116, no. 3, pp. 571–580. https://doi.org/10.1172/JCI27989Mechanism of action of fbrates on lipid and lipoprotein metabolism / B. Staels [et al.] // Circulation. – 1998. – Vol. 98, N 19. – P. 2088–2093. https://doi.org/10.1161/01.cir.98.19.2088Staels B., Dallongeville J., Auwerx J., Schoonjans K., Leitersdorf E., Fruchart J.-Ch. Mechanism of action of fbrates on lipid and lipoprotein metabolism. Circulation, 1998, vol. 98, no. 19, pp. 2088–2093. https://doi.org/10.1161/01.cir.98.19.2088The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism / S. Kersten [et al.] // FASEB J. – 2001. – Vol. 15, N 11. – P. 1971–1978. https://doi.org/10.1096/fj.01-0147comKersten S., Mandard S., Escher P., Gonzalez F. J., Tafuri S., Desvergne B., Wahli W. The peroxisome proliferator-activated receptor alpha regulates amino acid metabolism. FASEB Journal, 2001, vol. 15, no. 11, pp. 1971–1978. https://doi.org/10.1096/fj.01-0147comPPAR alpha regulation of the immune response and autoimmune encephalomyelitis / Y. Yang [et al.] // PPAR Res. – 2008. – Vol. 2008. – Art. ID 546753. https://doi.org/10.1155/2008/546753Yang Y., Gocke A. R., Lovett-Racke A., Drew P. D., Racke M. K. PPAR alpha regulation of the immune response and autoimmune encephalomyelitis. PPAR Research, 2008, vol. 2008, art. ID 546753. https://doi.org/10.1155/2008/546753Cannabinoids and PPARalpha signaling / Y. Sun [et al.] // Biochem. Soc. Trans. – 2006. – Vol. 34, N 6. – P. 1095–1097. https://doi.org/10.1042/BST0341095Sun Y., Alexander S. P. H., Kendall D. A., Bennett A. J. Cannabinoids and PPARalpha signaling. Biochemical Society Transactions, 2006, vol. 34, no. 6, pp. 1095–1097. https://doi.org/10.1042/BST0341095Linoleic acid-enriched phospholipids act through peroxisome proliferator-activated receptors alpha to stimulate hepatic apolipoprotein A-I secretion / N. R. Pandey [et al.] // Biochemistry. – 2008. – Vol. 47, N 6. – P. 1579–1587. https://doi.org/10.1021/bi702148fPandey N. R., Renwick J., Misquith A., Sokoll K., Sparks D. L. Linoleic acid-enriched phospholipids act through peroxisome proliferator-activated receptors alpha to stimulate hepatic apolipoprotein A-I secretion. Biochemistry, 2008, vol. 47, no. 6, pp. 1579–1587. https://doi.org/10.1021/bi702148fThe organization, promoter analysis, and expression of the human PPARgamma gene / L. Fajas [et al.] // J. Biol. Chem. – 1997. – Vol. 272, N 30. – P. 18779–18789. https://doi.org/10.1074/jbc.272.30.18779Fajas L., Auboeuf D., Raspé E., Schoonjans K., Lefebvre A.-M., Saladin R. [et al.]. The organization, promoter analysis, and expression of the human PPARgamma gene. Journal of Biological Chemistry, 1997, vol. 272, no. 30, pp. 18779–18789. https://doi.org/10.1074/jbc.272.30.18779PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes / T. Han [et al.] // J. Pharmacol. Sci. – 2019. – Vol. 139, N 1. – P. 1–8. https://doi.org/10.1016/j.jphs.2018.09.013Han T., Lv Y., Wang S., Hu T., Hong H., Fu Z. PPARγ overexpression regulates cholesterol metabolism in human L02 hepatocytes. Journal of Pharmacological Sciences, 2019, vol. 139, no. 1, pp. 1–8. https://doi.org/10.1016/j.jphs.2018.09.013Wang, S. PPARγ signaling and emerging opportunities for improved therapeutics / S. Wang, E. J. Dougherty, R. L. Danner // Pharmacol. Res. – 2016. – Vol. 111. – P. 76–85. https://doi.org/10.1016/j.phrs.2016.02.028Wang S., Dougherty E. J., Danner R. L. PPARγ signaling and emerging opportunities for improved therapeutics. Pharmacological Research, 2016, vol. 111, pp. 76–85. https://doi.org/10.1016/j.phrs.2016.02.028PPARgamma in the control of brown adipocyte differentiation / J. Nedergaard [et al.] // Biochim. Biophys. Acta – Mol. Cell Biol. Lipids. – 2005. – Vol. 1740, N 2. – P. 293–304. https://doi.org/10.1016/j.bbadis.2005.02.003Nedergaard J., Petrovic N., Lindgren E. M., Jacobsson A., Cannon B. PPARgamma in the control of brown adipocyte differentiation. Biochimica et Biophysica Acta (BBA) – Molecular Basis of Disease, 2005, vol. 1740, no. 2, pp. 293–304. https://doi.org/10.1016/j.bbadis.2005.02.003Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs / J. R. Barson [et al.] // Alcohol. – 2009. – Vol. 43, N 6. – P. 433–441. https://doi.org/10.1016/j.alcohol.2009.07.003Barson J. R., Karatayev O., Chang G.-Q., Johnson D. F., Bocarsly M. E., Hoebel B. G., Leibowitz S. F. Positive relationship between dietary fat, ethanol intake, triglycerides, and hypothalamic peptides: counteraction by lipid-lowering drugs. Alcohol, 2009, vol. 43, no. 6, pp. 433–441 https://doi.org/10.1016/j.alcohol.2009.07.003Activation of nuclear PPARγ receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking / S. Stopponi [et al.] // Biol. Psychiatry. – 2011. – Vol. 69, N 7. – P. 642–649. https://doi.org/10.1016/j.biopsych.2010.12.010Stopponi S., Somaini L., Cippitelli A., Cannella N., Braconi S., Kallupi M. [et al.]. Activation of nuclear PPARγ receptors by the antidiabetic agent pioglitazone suppresses alcohol drinking and relapse to alcohol seeking. Biological Psychiatry, 2011, vol. 69, no. 7, pp. 642–649. https://doi.org/10.1016/j.biopsych.2010.12.010Activation of PPARγ by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats / S. Stopponi [et al.] // Alcoholism: Clin. Exp. Res. – 2013. – Vol. 37, N 8. – P. 1351–1360. https://doi.org/10.1111/acer.12091Stopponi S., de Guglielmo G., Somaini L., Cippitelli A., Cannella N., Kallupi M. [et al.]. Activation of PPARγ by pioglitazone potentiates the effects of naltrexone on alcohol drinking and relapse in msP rats. Alcoholism: Clinical and Experimental Research, 2013, vol. 37, no. 8, pp. 1351–1360. https://doi.org/10.1111/acer.12091Different immune cells mediate mechanical pain hypersensitivity in male and female mice / R. E. Sorge [et al.] // Nat. Neurosci. – 2015. – Vol. 18, N 8. – P. 1081–1083. https://doi.org/10.1038/nn.4053Sorge R. E., Mapplebeck J. C. S., Rosen S., Beggs S., Taves S., Alexander J. K. [et al.]. Different immune cells mediate mechanical pain hypersensitivity in male and female mice. Nature Neuroscience, 2015, vol. 18, no. 8, pp. 1081–1083. https://doi.org/10.1038/nn.4053Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans / Y. A. Blednov [et al.] // Alcoholism: Clin. Exp. Res. – 2015. – Vol. 39, N 1. – P. 136–145. https://doi.org/10.1111/acer.12610Blednov Y. A., Benavidez J. M., Black M., Ferguson L. B., Schoenhard G. L., Goate A. M. [et al.]. Peroxisome proliferator-activated receptors α and γ are linked with alcohol consumption in mice and withdrawal and dependence in humans. Alcoholism: Clinical and Experimental Research, 2015, vol. 39, no. 1, pp. 136–145. https://doi.org/10.1111/acer.12610PPAR agonists: I. Role of receptor subunits in alcohol consumption in male and female mice / Y. A. Blednov [et al.] // Alcoholism: Clin. Exp. Res. – 2016. – Vol. 40, N 3. – P. 553–562. https://doi.org/10.1111/acer.12976Blednov Y. A., Black M., Benavidez J. M., Stamatakis E. E., Harris R. A. PPAR agonists: I. Role of receptor subunits in alcohol consumption in male and female mice. Alcoholism: Clinical and Experimental Research, 2016, vol. 40, no. 3, pp. 553–562. https://doi.org/10.1111/acer.12976PPAR agonists: II. Fenofbrate and tesaglitazar alter behaviors related to voluntary alcohol consumption / Y. A. Blednov [et al.] // Alcoholism: Clin. Exp. Res. – 2016. – Vol. 40, N 3. – P. 563–571. https://doi.org/10.1111/acer.12972Blednov Y. A., Black M., Benavidez J. M., Stamatakis E. E., Harris R. A. PPAR agonists: II. Fenofbrate and tesaglitazar alter behaviors related to voluntary alcohol consumption. Alcoholism: Clinical and Experimental Research, 2016, vol. 40, no. 3, pp. 563–571. https://doi.org/10.1111/acer.12972Fenofbrate – a lipid-lowering drug – reduces voluntary alcohol drinking in rats / E. Karahanian [et al.] // Alcohol. – 2014. – Vol. 48, N 7. – P. 665–670. https://doi.org/10.1016/j.alcohol.2014.08.004Karahanian E., Quintanilla M. E., Fernandez K., Israel Y. Fenofbrate – a lipid-lowering drug – reduces voluntary alcohol drinking in rats. Alcohol, 2014, vol. 48, no. 7, pp. 665–670. https://doi.org/10.1016/j.alcohol.2014.08.004Влияние активаторов и ингибиторов каталазы на показатели фармакокинетики этанола и активность ферментов метаболизма этанола и ацетальдегида печени и мозга крыс / Л. Р. Бардина [и др.] // Биомед. химия. – 2010. – Т. 56, № 4. – С. 499–505.Bardina L. R., Pron’ko P. S., Satanovskaya V. I., Alieva E. V. Effects of catalase activators and inhibitors on ethanol pharmacokinetics and the activity of enzymes involved in metabolism of ethanol and acetaldehyde in the liver and brain of rats. Biomeditsinskaya khimiya [Biomedical chemistry], 2010, vol. 56, no. 4, pp. 499–505 (in Russian).PPAR agonists regulate brain gene expression: Relationship to their effects on ethanol consumption / L. B. Ferguson [et al.] // Neuropharmacology. – 2014. – Vol. 86. – P. 397–407. https://doi.org/10.1016/j.neuropharm.2014.06.024Ferguson L. B., Most D., Blednov Y. A., Harris R. A. PPAR agonists regulate brain gene expression: Relationship to their effects on ethanol consumption. Neuropharmacology, 2014, vol. 86, pp. 397–407 https://doi.org/10.1016/j.neuropharm.2014.06.024Новые фармакологические подходы в терапии алкогольной зависимости: агонисты PPAR-рецепторов / А. Г. Шляхтун [и др.] // Современные проблемы биохимии и молекулярной биологии : сб. науч. ст., Гродно, 17–18 мая 2018 г. / НАН Беларуси, Ин-т биохимии биол. активных соединений НАН Беларуси ; под общ. ред. И. Н. Семенени, А. Г. Мойсеенка. – Минск, 2018. – С. 730–735.Shlyakhtun A. G., Buben A. L., Loban’ Yu. V., Satanovskaya V. I., Pron’ko P. S. New pharmacological approaches in the treatment of alcohol dependence: PPAR receptor agonists. Sovremennye problemy biokhimii i molekulyarnoi biologii: sbornik nauchnykh statei (Grodno, 17–18 maya 2018 goda) [Modern problems of biochemistry and molecular biology: a collection of scientifc articles (Grodno, May 17–18, 2018)]. Minsk, 2018, pp. 730–735 (in Russian).Kelley, K. W. Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders / K. W. Kelley, R. Dantzer // Brain Behav. Immun. – 2011. – Vol. 25, Suppl. 1. – P. S13–S20. https://doi.org/10.1016/j.bbi.2010.12.013Kelley K. W., Dantzer R. Alcoholism and inflammation: neuroimmunology of behavioral and mood disorders. Brain, Behavior, and Immunity, 2011, vol. 25, suppl. 1, pp. S13–S20. https://doi.org/10.1016/j.bbi.2010.12.013Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation / C. Blanquart [et al.] // J. Steroid. Biochem. Mol. Biol. – 2003. – Vol. 85, N 2–5. – P. 267–273. https://doi.org/10.1016/S0960-0760(03)00214-0Blanquart C., Barbier O., Fruchart J. Ch., Staels B., Glineur C. Peroxisome proliferator-activated receptors: regulation of transcriptional activities and roles in inflammation. Journal of Steroid Biochemistry and Molecular Biology, 2003, vol. 85, no. 2–5, pp. 267–273. https://doi.org/10.1016/S0960-0760(03)00214-0Peroxisome proliferator-activated receptor (PPAR)-gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels / S. Aleshin [et al.] // Mol. Pharmacol. – 2009. – Vol. 76, N 2. – P. 414–424. https://doi.org/10.1124/mol.109.056010Aleshin S., Grabeklis S., Hanck T., Sergeeva M., Reiser G. Peroxisome proliferator-activated receptor (PPAR)- gamma positively controls and PPARalpha negatively controls cyclooxygenase-2 expression in rat brain astrocytes through a convergence on PPARbeta/delta via mutual control of PPAR expression levels. Molecular Pharmacology, 2009, vol. 76, no. 2, pp. 414–424. https://doi.org/10.1124/mol.109.056010Nan, Y.-M. Peroxisome proliferator-activated receptor α, a potential therapeutic target for alcoholic liver disease / Y.-M. Nan, R.-Q. Wang, N. Fu // World J Gastroenterol. – 2014. – Vol. 20, N 25. – P. 8055–8060. https://doi.org/10.3748/wjg.v20.i25.8055Nan Y.-M., Wang R.-Q., Fu N. Peroxisome proliferator-activated receptor α, a potential therapeutic target for alcoholic liver disease. World Journal of Gastroenterology, 2014, vol. 20, no. 25, pp. 8055–8060. https://doi.org/10.3748/wjg.v20.i25.8055Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepatitis in mice / L. Kong [et al.] // Lipids Health. Dis. – 2011. – Vol. 10. – Art. 246. https://doi.org/10.1186/1476-511X-10-246Kong L., Ren W., Li W., Zhao S., Mi H., Wang R., Zhang Y., Wu W., Nan Y., Yu J. Activation of peroxisome proliferator activated receptor alpha ameliorates ethanol induced steatohepatitis in mice. Lipids in Health and Diseases, 2011, vol. 10, art. 246. https://doi.org/10.1186/1476-511X-10-246Alteration of hepatic nuclear receptor-mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking / C. Wu [et al.] // Hepatology. – 2011. – Vol. 54, N 6. – P. 1966–1974. https://doi.org/10.1002/hep.24645Wu C., Gilroy R., Taylor R., Olyaee M., Abdulkarim B., Forster J., O’Neil M., Damjanov I., Wan Y.-J. Y. Alteration of hepatic nuclear receptor- mediated signaling pathways in hepatitis C virus patients with and without a history of alcohol drinking. Hepatology, 2011, vol. 54, no. 6, pp. 1966–1974. https://doi.org/10.1002/hep.24645Hepatic peroxisome proliferator-activated receptor gamma signaling contributes to alcohol-induced hepatic steatosis and inflammation in mice / W. Zhang [et al.] // Alcohol Clin. Exp. Res. – 2016. – Vol. 40, N 5. – P. 988–999. https://doi.org/10.1111/acer.13049Zhang W., Sun Q., Zhong W., Sun X., Zhou Z. Hepatic peroxisome proliferator-activated receptor gamma signaling contributes to alcohol-induced hepatic steatosis and inflammation in mice. Alcoholism: Clinical and Experimental Research, 2016, vol. 40, no. 5, pp. 988–999. https://doi.org/10.1111/acer.13049The ameliorating effect of rosiglitazone on experimental nonalcoholic steatohepatitis is associated with regulating adiponectin receptor expression in rats / S. Liu [et al.] // Eur. J. Pharmacol. – 2011. – Vol. 650, N 1. – P. 384–389. https://doi.org/10.1016/j.ejphar.2010.09.082Liu S., Wu H.-J., Zhang Z.-Q., Chen Q., Liu B., Wu J.-P., Zhu L. The ameliorating effect of rosiglitazone on experimental nonalcoholic steatohepatitis is associated with regulating adiponectin receptor expression in rats. European Journal of Pharmacology, 2011, vol. 650, no. 1, pp. 384–389. https://doi.org/10.1016/j.ejphar.2010.09.082Zhang, F. Peroxisome proliferator-activated receptor-γ cross-regulation of signaling events implicated in liver fbrogenesis / F. Zhang, Y. Lu, S. Zheng // Cell. Signal. – 2012. – Vol. 24, N 3. – P. 596–605. https://doi.org/10.1016/j.cellsig.2011.11.008Zhang F., Lu Y., Zheng S. Peroxisome proliferator-activated receptor-γ cross-regulation of signaling events implicated in liver fbrogenesis. Cellular Signalling, 2012, vol. 24, no. 3, pp. 596–605. https://doi.org/10.1016/j.cellsig.2011.11.008PPARδ agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair / M. Pang [et al.] // J. Hepatol. – 2009. – Vol. 50, N 6. – P. 1192–1201. https://doi.org/10.1016/j.jhep.2009.01.021Pang M., de la Monte S. M., L. Longato, M. Tong, He J., Chaudhry R., Duan K., Ouh J., Wands J. R. PPARδ agonist attenuates alcohol-induced hepatic insulin resistance and improves liver injury and repair. Journal of Hepatology, 2009, vol. 50, no. 6, pp. 1192–1201. https://doi.org/10.1016/j.jhep.2009.01.021Differential activation of catalase expression and activity by PPAR agonists: implications for astrocyte protection in anti-glioma therapy / N. K. H. Khoo [et al.] // Redox Biol. – 2013. – Vol. 1, N 1. – P. 70–79. https://doi.org/10.1016/j.redox.2012.12.006Khoo N. K. H., Hebbar S., Zhao W., Moore S. A., Domann F. E., Robbins M. E. Differential activation of catalase expression and activity by PPAR agonists: implications for astrocyte protection in anti-glioma therapy. Redox Biology, 2013, vol. 1, no. 1, pp. 70–79. https://doi.org/10.1016/j.redox.2012.12.006Fenofbrate decreases radiation sensitivity via peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells / X. Liu [et al.] // Radiat. Oncol. J. – 2012. – Vol. 30, N 2. – P. 88–95. https://doi.org/10.3857/roj.2012.30.2.88Liu X., Jang S. S., An Z., Song H., Kim W.-D., Yu J.-R., Park W.-Y. Fenofbrate decreases radiation sensitivityvia peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells. Radiationvia peroxisome proliferator-activated receptor α-mediated superoxide dismutase induction in HeLa cells. RadiationOncology Journal, 2012, vol. 30, no. 2, pp. 88–95. https://doi.org/10.3857/roj.2012.30.2.88Oncology Journal, 2012, vol. 30, no. 2, pp. 88–95. https://doi.org/10.3857/roj.2012.30.2.88

The authors declare that there are no conflicts of interest present.