NMR metabolic profiling of the liver following administrationof alcohol andthemushroom Ganoderma lucidum in rats. M. S. Krestina, O. B. Shevelev, I. V. Koptyug, L. A. Gerlinskaya, S. E. Peltek, A. E. Akulov ВАВИЛОВСКИЙ

Abstract:

We have evaluated the efficiency of a metabonomic approach to metabolic phenotyping and detection of early metabolic changes under a toxic influence. For this purpose, a metabolic profiling of rat liver was performed with 1H NMR spectroscopy. Rat tissues from animals in three groups were analyzed. Group C consisted of control animals; animals in group A received alcohol repeatedly (15 % ethanol); and animals in group A+ R received alcohol in combination with a hepatoprotective herbal medicine (Reishi, Ganoderma lucidum) repeatedly. Noteworthy, alcohol consumption did not cause pathological changes, but stimulated hepatocyte proliferation. Our data suggest that changes in metabolite concentrations in A represent a typical metabolic response to alcohol consumption, namely decrease in glycine, leucine, isoleucine, valine, choline and lactate content pornoa.tube/tags/, and increase in TMAO content. Treatment with Reishi (A+ R) had positive effects, in that it restored the levels of glycine, valine and TMAO. Furthermore, increase in NAD, ATP, UTP, succinate, pyranose, and acetate concentrations was observed in A+ R. A correlation was found between the valine, isoleucine, lactate, choline, and pyranose content and the number of binuclear hepatocytes. Binuclear hepatocytes indicate proliferative activity, and the concentration of the metabolites participating in the formation of new hepatic cells decreases. Thus, the study of liver tissues by 1H NMR spectroscopy allows for detection of early changes in metabolite concentrations following chronic consumption of alcohol at insignificant doses. Consequently, 1H NMR spectroscopy can serve as a promising approach to detecting alcohol-related liver diseases pathologies and assessing the efficiency of the therapy used.

About The Authors:

M. S. Krestina. International Tomography Center of the Siberian Branch of the Russian Academy of Sciences; Novosibirsk State University, Russian Federation, Novosibirsk

O. B. Shevelev. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

I. V. Koptyug. International Tomography Center of the Siberian Branch of the Russian Academy of Sciences, Russian Federation, Novosibirsk

L. A. Gerlinskaya. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

S. E. Peltek. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

A. E. Akulov. Institute of Cytology and Genetics SB RAS, Russian Federation, Novosibirsk

References:

1. Bollard M.E., Contel N.R., Ebbels T.M., Smith L., Beckonert O., Cantor G.H., Lehman-McKeeman L., Holmes E.C., Lindon J.C., Nicholson J.K., Keun H.C. NMR-based metabolic profiling identifies biomarkers of liver regeneration following partial hepatectomy in the rat. J. Proteome Res. 2010;9(1):59-69. DOI:10.1021/pr900200v

2. Bruha R., Dvorak K., Petrtyl J. Alcoholic liver disease. World. J. Hepatol. 2012;4(3):81-90. DOI:10.4254/wjh.v4.i3.81

3. Fehér P., Ujhelyi Z., Vecsernyés M., Fenyvesi F., Damache G., Ardelean A., Costache M., Dinischiotu A., Hermenean A., Bácskay I. Hepatoprotective effects of a self-micro emulsifying drug delivery system containing Silybum marianum native seed oil against experimentally induced liver injury. Pharmazie. 2015;70(4):231-238. DOI: 1691/ph.2015.4146

4. Feng J., Isern N.J., Burton S.D., Zhi Hu J. Studies of secondary melanoma on C57BL/6J mouse liver using 1H NMR metabolomic. Metabolites. 2013;3(4):1011-1035. DOI: 10.3390/metabo3041011

5. Gao Y., Zhou S., Jiang W., Huang M., Dai X. Effects of ganopoly (a Ganoderma lucidum polysaccharide extract) on the immune functions in advanced-stage cancer patients. Immunol. Invest. 2003;32(3):201-215. DOI: 10.1081/IMM-120022979

6. Gika H.G., Wilson I.D. Global metabolic profiling for the study of alcohol-related disorders. Bioanalysis. 2014;6(1):59-77. DOI: 10.4155/bio.13.301

7. Jang Z.H., Chung H.C., Ahn Y.G., Kwon Y.K., Kim J.S., Ryu J.H., Ryu Do H., Kim C.H., Hwang G.S. Metabolic profiling of analcoholic fatty liver in zebrafish (Danio rerio). Mol. Biosyst. 2012;8(7):2001-2009. DOI:10.1039/c2mb25073j

8. Kato A., Tanaka H., Kawaguchi T., Kanazawa H., Iwasa M., Sakaida I., Moriwaki H., Murawaki Y., Suzuki K., Okita K. Nutritional management contributes to improvement in minimal hepatic encephalopathy and quality of life in patients with liver cirrhosis: A preliminary, prospective, open-label study. Hepatol. Res. 2013;43(5):452-458. DOI: 10.1111/j.1872-034X.2012.01092.x

9. Koeth R.A., Wang Z., Levison B.S., Buffa J.A., Org E., Sheehy B.T., Britt E.B., Fu X., Wu Y., Li L., Smith J.D., DiDonato J.A., Chen J., Li H., Wu G.D., Lewis J.D., Warrier M., Brown J.M., Krauss R.M., Tang W.H., Bushman F.D., Lusis A.J., Hazen S.L. Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis. Nat. Med. 2013;19(5):576-585. DOI: 10.1038/nm.3145

10. Kushnerova N.F., Fedoreev S.A., Fomenko S.E., Sprygin V.G., Kulesh N.I., Mishchenko N.P., Veselova M.V., Momot T.V. Hepatoprotective properties of isoflavonoids from roots of Maackia amurensis on experimental carbon tetrachloride-induced hepatic damage. Eksp. Klin. Farmakol. 2014;77(2):26-30.

11. Kwon S.C., Kim Y.B. Antifibrotic activity a fermentation filtrate of Ganoderma lucidum. Lab. Anim. Res. 2011;27(4):369-371. DOI: 10.5625/lar.2011.27.4.369

12. Lieber C.S. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol. 2004;34(1):9-19. DOI: 10.1016/j.alcohol.2004.07.008

13. Malaguarnera M., Risino C., Cammalleri L., Malaguarnera L., Astuto M., Vecchio I., Rampello L. Branched chain amino acids supplemented with L-acetylcarnitine versus BCAA treatment in hepatic coma: a randomized and controlled double blind study. Eur. J. Gastroenterol. Hepatol. 2009;21(7):762-770. DOI:10.1097/MEG.0b013e328309c791

14. Nelson D.L., Cox M.M. Lehninger Principles of Biochemistry. W.H. Freeman; Fifth Edition, 2008.

15. Nicholas P.C., Kim D., Crews F.T., Macdonald J.M. 1H NMR-based metabolomic analysis of liver, serum, and brain following ethanol administration in rats. Chem. Res. Toxicol. 2008;21(2):408-420. DOI:10.1021/tx700324t

16. Psychogios N., Hau D.D., Peng J., Gui A.C., Mandal R., Bouatra S., Sinelnikov I., Krishnamurthy R., Eisner R., Gautam B., Young N., Xia J., Knox C., Dong E., Huang P., Hollander Z., Pedersen T.L., Smith S.R., Bamforth F., Greiner R., McManus B., Newman J.W., Goodfriend T., Wishart D.S. The human serum metabolome. PLoS ONE. 2011;6(2):e16957. DOI: 10.1371/journal.pone.0016957

17. Romero-Martínez Á., Moya-Albiol L. Neuropsychology of perpetrators of domestic violence: the role of traumatic brain injury and alcohol abuse and/or dependence. Rev. Neurol. 2013;57(11):515-522.

18. Roslundet M.U., Tahtinen P., Niemitz M., Sjoholm R. Complete assignments of the 1H and 13C chemical shifts and JH,H coupling constants in NMR spectra of d-glucopyranose and all d-glucopyranosyld-glucopyranosides. Carbohydr. Res. 2008;343(1):101-112. DOI: 10.1016/j.carres.2007.10.008

19. Shayakhmetova G.M., Bondarenko L.B., Kovalenko V.M., Kharchenko O.L., Bohun L.I., Omelchenko Y.O. Multiparameter rodent chronic model for complex evaluation of alcoholism-mediated metabolic violations. J. Basic Clin. Physiol. Pharmacol. 2015;26(1):43-51. DOI: 10.1515/jbcpp-2013-0163

20. Shevelev O.B., Akulov A.E., Dotsenko A.S., Kontsevaya G.V., Zolotykh M.A., Gerlinskaya L.A., Veprev S.G., Goryachkovskaya T.N., Zhukova N.A., Kolchanov N.A., Pel’tek S.E., Moshkin M.P. Neurometabolic effect of Altaian fungus Ganoderma lucidum (Reishi mushroom) in rats under moderate alcohol consumption. Alcohol.: Clin. Exp. Res. 2015;39(7):1128-1136. DOI: 10.1111/acer.12758

21. Shi Y., Sun J., He H., Guo H., Zhang S. Hepatoprotective effects of Ganoderma lucidum peptides against D-galactosamine-induced liver injury in mice. J. Ethnopharmacol. 2008;117(3):415-419. DOI:10.1016/j.jep.2008.02.023

22. Shieh Y.H., Liu C.F., Huang Y.K., Yang J.Y., Wu I.L., Lin C.H., Li S.C. Evaluation of the hepatic and renal-protective effects of Ganoderma lucidum in mice. Am. J. Chin. Med. 2001;29(3/4):501-507. DOI:10.1142/S0192415X01000526

23. Siler S.Q., Neese R.A., Christiansen M.P., Hellerstein M.K. The inhibition of gluconeogenesis following alcohol in humans. Am. J. Physiol. 1998;275(5 Pt 1):E897-E907.

24. Tang W.H., Wang Z., Levison B.S., Koeth R.A., Britt E.B., Fu X., Wu Y., Hazen S.L. Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk. N. Engl. J. Med. 2013;368(17):1575-1584. DOI:10.1056/NEJMoa1109400

25. Wang M.Y., Liu Q., Che Q.M., Lin Z.B. Effects of total triterpenoids extract from Ganoderma lucidum (Curt: Fr) P Karst (Reishi mushroom) on experimental liver injury models induced by carbon tetrachloride or D-galactosamine in mice. Acta Pharmaceut Sin. 2000;35:326-329.

26. Wen H., Kang S., Song Y., Song Y., Sung S.H., Park S. Differentiation of cultivation sources of Ganoderma lucidum by NMR-based metabolomics approach. Phytochem. Anal. 2010;21(1):73-79. DOI:10.1002/pca.1166

27. Wu Y.W., Fang H.L., Lin W.C. Post-treatment of Ganoderma lucidum reduced liver fibrosis induced by thioacetamide in mice. Phytother. Res. 2010;24(4):494-499. DOI: 10.1002/ptr.2949

28. Zhao H.B., Lin S.Q., Liu J.H., Lin Z.B. Polysaccharide extract isolated from ganoderma lucidum protects rat cerebral cortical neurons from hypoxia/reoxygenation injury. J. Pharmacol. Sci. 2004;95(2):294-298. DOI:10.1254/jphs.SC0040011