Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

The Role of MIF in Hepatic Function, Oxidative Stress, and Inflammation in Thioacetamide-induced Liver Injury in Mice: Protective Effects of Betaine

Author(s): Dušan Vukićević, Branislav Rovčanin, Kristina Gopčević, Sanja Stanković, Danijela Vučević, Bojan Jorgačević, Dušan Mladenović, Milena Vesković, Janko Samardžić, Rada Ješić and Tatjana Radosavljević*

Volume 28, Issue 16, 2021

Published on: 04 November, 2020

Page: [3249 - 3268] Pages: 20

DOI: 10.2174/0929867327666201104151025

Price: $65

Abstract

Background: Macrophage migration inhibitory factor (MIF) is a multipotent cytokine that contributes to the inflammatory response to chemical liver injury. This cytokine exhibits pro- and anti-inflammatory effects depending on the etiology and stage of liver disease.

Objective: Our study aimed to investigate the role of MIF in oxidative stress and inflammation in the liver, and modulatory effects of betaine on MIF in thioacetamide (TAA)-induced chronic hepatic damage in mice.

Methods: The experiment was performed on wild type and knockout MIF-/- C57BL/6 mice. They were divided into the following groups: control; Bet-group that received betaine (2% wt/v dissolved in drinking water); MIF-/- mice group; MIF-/-+Bet; TAA-group that received TAA (200 mg/kg b.w.), intraperitoneally, 3x/week/8 weeks); TAA+Bet; MIF-/-+TAA, and MIF-/-+TAA+Bet. In TAA- and Bet-treated groups, animals received the same doses. After eight weeks of treatment, blood samples were collected for biochemical analysis, and liver specimens were prepared for the assessment of parameters of oxidative stress and inflammation.

Results: In MIF-/-mice, TAA reduced transaminases, γ-glutamyltranspeptidase, bilirubin, malondialdehyde (MDA), oxidative protein products (AOPP), total oxidant status (TOS), C-reactive protein (CRP), IL-6, IFN-γ, and increased thiols and total antioxidant status (TAS). Betaine attenuated the mechanism of MIF and mediated effects in TAA-induced liver injury, reducing transaminases, γ-glutamyltranspeptidase, bilirubin, MDA, AOPP, TOS, CRP, IL-6, IFN-g, and increasing thiols.

Conclusion: MIF is a mediator in hepatotoxic, pro-oxidative, and proinflammatoryeffects of TAA-induced liver injury. MIF-targeted therapy can potentially mitigate oxidative stress and inflammation in the liver, but the exact mechanism of its action requires further investigation. Betaine increases anti-oxidative defense and attenuates hepatotoxic effects of MIF, suggesting that betaine can be used for the prevention and treatment of liver damage.

Keywords: Thioacetamide, liver damage, inflammation, macrophage migration inhibitory factor, betaine, mice.

« Previous
[1]
Gulati, K.; Reshi, M.R.; Rai, N.; Ray, A. Hepatotoxicity: its mechanisms, experimental evaluation and protective strategies. Am. J. Pharmacol., 2018, 1(1), 1004.
[2]
Singh, D.; Cho, W.C.; Upadhyay, G. Drug-induced liver toxicity and prevention by herbal antioxidants: an overview. Front. Physiol., 2016, 6, 363.
[http://dx.doi.org/10.3389/fphys.2015.00363] [PMID: 26858648]
[3]
Farzaei, M.H.; Zobeiri, M.; Parvizi, F.; El-Senduny, F.F.; Marmouzi, I.; Coy-Barrera, E.; Naseri, R.; Nabavi, S.M.; Rahimi, R.; Abdollahi, M. Curcumin in liver diseases: a systemic review of the cellular mechanisms of oxidative stress and clinical perspective. Nutrients, 2018, 10(7), 855.
[http://dx.doi.org/10.3390/nu10070855] [PMID: 29966389]
[4]
Asrani, S.K.; Devarbhavi, H.; Eaton, J.; Kamath, P.S. Burden of liver diseases in the world. J. Hepatol., 2019, 70(1), 151-171.
[http://dx.doi.org/10.1016/j.jhep.2018.09.014] [PMID: 30266282]
[5]
Tuñón, M.-J.; Alvarez, M.; Culebras, J.-M.; González-Gallego, J. An overview of animal models for investigating the pathogenesis and therapeutic strategies in acute hepatic failure. World J. Gastroenterol., 2009, 15(25), 3086-3098.
[http://dx.doi.org/10.3748/wjg.15.3086] [PMID: 19575487]
[6]
Liu, Y.; Meyer, C.; Xu, C.; Weng, H.; Hellerbrand, C.; ten Dijke, P.; Dooley, S. Animal models of chronic liver diseases. Am. J. Physiol. Gastrointest. Liver Physiol., 2013, 304(5), G449-G468.
[http://dx.doi.org/10.1152/ajpgi.00199.2012] [PMID: 23275613]
[7]
Heidari, R.; Niknahad, H.; Sadeghi, A.; Mohammadi, H.; Ghanbarinejad, V.; Ommati, M.M.; Hosseini, A.; Azarpira, N.; Khodaei, F.; Farshad, O.; Rashidi, E.; Siavashpour, A.; Najibi, A.; Ahmadi, A.; Jamshidzadeh, A. Betaine treatment protects liver through regulating mitochondrial function and counteracting oxidative stress in acute and chronic animal models of hepatic injury. Biomed. Pharmacother., 2018, 103, 75-86.
[http://dx.doi.org/10.1016/j.biopha.2018.04.010] [PMID: 29635131]
[8]
Bashandy, S.A.E.; Ebaid, H.; Abdelmottaleb Moussa, S.A.; Alhazza, I.M.; Hassan, I.; Alaamer, A.; Al Tamimi, J. Potential effects of the combination of nicotinamide, vitamin B2 and vitamin C on oxidative-mediated hepatotoxicity induced by thioacetamide. Lipids Health Dis., 2018, 17(1), 29.
[http://dx.doi.org/10.1186/s12944-018-0674-z] [PMID: 29444683]
[9]
Hajovsky, H.; Hu, G.; Koen, Y.; Sarma, D.; Cui, W.; Moore, D.S.; Staudinger, J.L.; Hanzlik, R.P. Metabolism and toxicity of thioacetamide and thioacetamide S-oxide in rat hepatocytes. Chem. Res. Toxicol., 2012, 25(9), 1955-1963.
[http://dx.doi.org/10.1021/tx3002719] [PMID: 22867114]
[10]
Li, S.; Tan, H.Y.; Wang, N.; Zhang, Z.J.; Lao, L.; Wong, C.W.; Feng, Y. The role of oxidative stress and antioxidants in liver diseases. Int. J. Mol. Sci., 2015, 16(11), 26087-26124.
[http://dx.doi.org/10.3390/ijms161125942] [PMID: 26540040]
[11]
Jorgačević, B.; Vučević, D.; Samardžić, J.; Mladenović, D.; Vesković, M.; Vukićević, D.; Ješić, R.; Radosavljević, T. The effect of CB1 antagonism on hepatic oxidative/nitrosative stress and inflammation in nonalcoholic fatty liver disease. Curr. Med. Chem., 2021, 28(1), 169-180.
[http://dx.doi.org/10.2174/0929867327666200303122734] [PMID: 32124686]
[12]
Cichoż-Lach, H.; Michalak, A. Oxidative stress as a crucial factor in liver diseases. World J. Gastroenterol., 2014, 20(25), 8082-8091.
[http://dx.doi.org/10.3748/wjg.v20.i25.8082] [PMID: 25009380]
[13]
Jorgačević, B.; Mladenović, D.; Ninković, M.; Vesković, M.; Dragutinović, V.; Vatazević, A.; Vučević, D.; Ješić Vukićević, R.; Radosavljević, T. Rimonabant improves oxidative/nitrosative stress in mice with nonalcoholic fatty liver disease. Oxid. Med. Cell. Longev., 2015, 2015, 842108.
[http://dx.doi.org/10.1155/2015/842108] [PMID: 26078820]
[14]
Grieb, G.; Merk, M.; Bernhagen, J.; Bucala, R. Macrophage migration inhibitory factor (MIF): a promising biomarker. Drug News Perspect., 2010, 23(4), 257-264.
[http://dx.doi.org/10.1358/dnp.2010.23.4.1453629] [PMID: 20520854]
[15]
Marin, V.; Odena, G.; Poulsen, K.; Tiribelli, C.; Bellentani, S.; Barchetti, A.; Bru, P.S.; Rosso, N.; Bataller, R.; Laura, E.; Nagy, L.E. Role of MIF in hepatic inflammatory diseases and fibrosis. In: MIF Family Cytokines in Innate Immunity and Homeostasis. Progress in Inflammation Research; Bucala, R.; Bernhagen, J., Eds.; Springer International. , 2017; pp. 109-134.
[http://dx.doi.org/10.1007/978-3-319-52354-5_7]
[16]
Heinrichs, D.; Knauel, M.; Offermanns, C.; Berres, M.L.; Nellen, A.; Leng, L.; Schmitz, P.; Bucala, R.; Trautwein, C.; Weber, C.; Bernhagen, J.; Wasmuth, H.E. Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74. Proc. Natl. Acad. Sci. USA, 2011, 108(42), 17444-17449.
[http://dx.doi.org/10.1073/pnas.1107023108] [PMID: 21969590]
[17]
Marin, V.; Poulsen, K.; Odena, G.; McMullen, M.R.; Altamirano, J.; Sancho-Bru, P.; Tiribelli, C.; Caballeria, J.; Rosso, N.; Bataller, R.; Nagy, L.E. Hepatocyte-derived macrophage migration inhibitory factor mediates alcohol-induced liver injury in mice and patients. J. Hepatol., 2017, 67(5), 1018-1025.
[http://dx.doi.org/10.1016/j.jhep.2017.06.014] [PMID: 28647568]
[18]
Ohta, S.; Kawakami, Y.; Okano, H. MIF: functions in brain and glioblastoma. Oncotarget, 2017, 8(29), 46706-46707.
[http://dx.doi.org/10.18632/oncotarget.18489] [PMID: 28636550]
[19]
Leyton-Jaimes, M.F.; Kahn, J.; Israelson, A. Macrophage migration inhibitory factor: a multifaceted cytokine implicated in multiple neurological diseases. Exp. Neurol., 2018, 301(Pt B), 83-91.
[http://dx.doi.org/10.1016/j.expneurol.2017.06.021] [PMID: 28679106]
[20]
Calandra, T.; Roger, T. Macrophage migration inhibitory factor: a regulator of innate immunity. Nat. Rev. Immunol., 2003, 3(10), 791-800.
[http://dx.doi.org/10.1038/nri1200] [PMID: 14502271]
[21]
Lehmann, L.E.; Weber, S.U.; Fuchs, D.; Book, M.; Klaschik, S.; Schewe, J.C.; Hoeft, A.; Stüber, F. Oxidoreductase Macrophage Migration Inhibitory Factor is simultaneously increased in leukocyte subsets of patients with severe sepsis. Biofactors, 2008, 33(4), 281-291.
[http://dx.doi.org/10.1002/biof.5520330404] [PMID: 19509463]
[22]
Sinitski, D.; Kontos, C.; Krammer, C.; Asare, Y.; Kapurniotu, A.; Bernhagen, J. Macrophage migration inhibitory factor (MIF)-based therapeutic concepts in atherosclerosis and inflammation. Thromb. Haemost., 2019, 119(4), 553-566.
[http://dx.doi.org/10.1055/s-0039-1677803] [PMID: 30716779]
[23]
Bilsborrow, J.B.; Doherty, E.; Tilstam, P.V.; Bucala, R. Macrophage migration inhibitory factor (MIF) as a therapeutic target for rheumatoid arthritis and systemic lupus erythematosus. Expert Opin. Ther. Targets, 2019, 23(9), 733-744.
[http://dx.doi.org/10.1080/14728222.2019.1656718] [PMID: 31414920]
[24]
Mizue, Y.; Ghani, S.; Leng, L.; McDonald, C.; Kong, P.; Baugh, J.; Lane, S.J.; Craft, J.; Nishihira, J.; Donnelly, S.C.; Zhu, Z.; Bucala, R. Role for macrophage migration inhibitory factor in asthma. Proc. Natl. Acad. Sci. USA, 2005, 102(40), 14410-14415.
[http://dx.doi.org/10.1073/pnas.0507189102] [PMID: 16186482]
[25]
Bruchfeld, A.; Carrero, J.J.; Qureshi, A.R.; Lindholm, B.; Barany, P.; Heimburger, O.; Hu, M.; Lin, X.; Stenvinkel, P.; Miller, E.J. Elevated serum macrophage migration inhibitory factor (MIF) concentrations in chronic kidney disease (CKD) are associated with markers of oxidative stress and endothelial activation. Mol. Med., 2009, 15(3-4), 70-75.
[http://dx.doi.org/10.2119/molmed.2008.00109] [PMID: 19081768]
[26]
Kleemann, R.; Bucala, R. Macrophage migration inhibitory factor: critical role in obesity, insulin resistance, and associated comorbidities. Mediators Inflamm., 2010, 2010, 610479.
[http://dx.doi.org/10.1155/2010/610479] [PMID: 20169173]
[27]
Hoi, A.Y.; Iskander, M.N.; Morand, E.F. Macrophage migration inhibitory factor: a therapeutic target across inflammatory diseases. Inflamm. Allergy Drug Targets, 2007, 6(3), 183-190.
[http://dx.doi.org/10.2174/187152807781696455] [PMID: 17897055]
[28]
Liu, A.; Fang, H.; Dirsch, O.; Jin, H.; Dahmen, U. Early release of macrophage migration inhibitory factor after liver ischemia and reperfusion injury in rats. Cytokine, 2012, 57(1), 150-157.
[http://dx.doi.org/10.1016/j.cyto.2011.11.009] [PMID: 22136975]
[29]
Akbar, S.M.; Abe, M.; Murakami, H.; Tanimoto, K.; Kumagi, T.; Yamashita, Y.; Michitaka, K.; Horiike, N.; Onji, M. Macrophage migration inhibitory factor in hepatocellular carcinoma and liver cirrhosis; relevance to pathogenesis. Cancer Lett., 2001, 171(2), 125-132.
[http://dx.doi.org/10.1016/S0304-3835(01)00606-1] [PMID: 11520595]
[30]
Nanji, A.A.; Lau, G.K.; Tipoe, G.L.; Yuen, S.T.; Chen, Y.X.; Thomas, P.; Lan, H.Y. Macrophage migration inhibitory factor expression in male and female ethanol-fed rats. J. Interferon Cytokine Res., 2001, 21(12), 1055-1062.
[http://dx.doi.org/10.1089/107999001317205187] [PMID: 11798463]
[31]
Akyildiz, M.; Gunsar, F.; Nart, D.; Sahin, O.; Yilmaz, F.; Akay, S.; Ersoz, G.; Karasu, Z.; Ilter, T.; Batur, Y.; Berdeli, A.; Akarca, U. Macrophage migration inhibitory factor expression and MIF gene -173 G/C polymorphism in nonalcoholic fatty liver disease. Eur. J. Gastroenterol. Hepatol., 2010, 22(2), 192-198.
[http://dx.doi.org/10.1097/MEG.0b013e328331a596] [PMID: 19829123]
[32]
Craig, S.A.S. Betaine in human nutrition. Am. J. Clin. Nutr., 2004, 80(3), 539-549.
[http://dx.doi.org/10.1093/ajcn/80.3.539] [PMID: 15321791]
[33]
Tsai, M.-T.; Chen, C.-Y.; Pan, Y.-H.; Wang, S.-H.; Mersmann, H.J.; Ding, S.-T. Alleviation of carbon-tetrachloride-induced liver injury and fibrosis by betaine supplementation in chickens. Evid. Based Complement. Alternat. Med., 2015, 2015, 725379.
[http://dx.doi.org/10.1155/2015/725379] [PMID: 26491462]
[34]
Zeisel, S.H.; Mar, M.H.; Howe, J.C.; Holden, J.M. Concentrations of choline-containing compounds and betaine in common foods. J. Nutr., 2003, 133(5), 1302-1307.
[http://dx.doi.org/10.1093/jn/133.5.1302] [PMID: 12730414]
[35]
Lever, M.; Slow, S. The clinical significance of betaine, an osmolyte with a key role in methyl group metabolism. Clin. Biochem., 2010, 43(9), 732-744.
[http://dx.doi.org/10.1016/j.clinbiochem.2010.03.009] [PMID: 20346934]
[36]
Day, C.R.; Kempson, S.A. Betaine chemistry, roles, and potential use in liver disease. Biochim. Biophys. Acta, 2016, 1860(6), 1098-1106.
[http://dx.doi.org/10.1016/j.bbagen.2016.02.001] [PMID: 26850693]
[37]
Jung, Y.S.; Kim, S.J.; Kwon, D.Y.; Ahn, C.W.; Kim, Y.S.; Choi, D.W.; Kim, Y.C. Alleviation of alcoholic liver injury by betaine involves an enhancement of antioxidant defense via regulation of sulfur amino acid metabolism. Food Chem. Toxicol., 2013, 62, 292-298.
[http://dx.doi.org/10.1016/j.fct.2013.08.049] [PMID: 23994088]
[38]
Bingül, İ.; Başaran-Küçükgergin, C.; Aydın, A.F.; Çoban, J.; Doğan-Ekici, I.; Doğru-Abbasoğlu, S.; Uysal, M. Betaine treatment decreased oxidative stress, inflammation, and stellate cell activation in rats with alcoholic liver fibrosis. Environ. Toxicol. Pharmacol., 2016, 45, 170-178.
[http://dx.doi.org/10.1016/j.etap.2016.05.033] [PMID: 27314760]
[39]
Bingül, İ.; Aydın, A.F.; Başaran-Küçükgergin, C.; Doğan-Ekici, I.; Çoban, J.; Doğru-Abbasoğlu, S.; Uysal, M. High- fat diet plus carbon tetrachloride-induced liver fibrosis is alleviated by betaine treatment in rats. Int. Immunopharmacol., 2016, 39, 199-207.
[http://dx.doi.org/10.1016/j.intimp.2016.07.028] [PMID: 27494683]
[40]
Veskovic, M.; Mladenovic, D.; Milenkovic, M.; Tosic, J.; Borozan, S.; Gopcevic, K.; Labudovic-Borovic, M.; Dragutinovic, V.; Vucevic, D.; Jorgacevic, B.; Isakovic, A.; Trajkovic, V.; Radosavljevic, T. Betaine modulates oxidative stress, inflammation, apoptosis, autophagy, and Akt/mTOR signaling in methionine-choline deficiency-induced fatty liver disease. Eur. J. Pharmacol., 2019, 848, 39-48.
[http://dx.doi.org/10.1016/j.ejphar.2019.01.043] [PMID: 30689995]
[41]
Heinrichs, D.; Berres, M.-L.; Coeuru, M.; Knauel, M.; Nellen, A.; Fischer, P.; Philippeit, C.; Bucala, R.; Trautwein, C.; Wasmuth, H.E.; Bernhagen, J. Protective role of macrophage migration inhibitory factor in nonalcoholic steatohepatitis. FASEB J., 2014, 28(12), 5136-5147.
[http://dx.doi.org/10.1096/fj.14-256776] [PMID: 25122558]
[42]
Lowry, O.H.; Rosebrough, N.J.; Farr, A.L.; Randall, R.J. Protein measurement with the Folin phenol reagent. J. Biol. Chem., 1951, 193(1), 265-275.
[http://dx.doi.org/10.1016/S0021-9258(19)52451-6] [PMID: 14907713]
[43]
Girotti, M.J.; Khan, N.; McLellan, B.A. Early measurement of systemic lipid peroxidation products in the plasma of major blunt trauma patients. J. Trauma, 1991, 31(1), 32-35.
[http://dx.doi.org/10.1097/00005373-199101000-00007] [PMID: 1846013]
[44]
Witko, V.; Nguyen, A.T.; Descamps-Latscha, B. Microtiter plate assay for phagocyte-derived taurine-chloramines. J. Clin. Lab. Anal., 1992, 6(1), 47-53.
[http://dx.doi.org/10.1002/jcla.1860060110] [PMID: 1542083]
[45]
Capeillère-Blandin, C.; Gausson, V.; Descamps-Latscha, B.; Witko-Sarsat, V. Biochemical and spectrophotometric significance of advanced oxidized protein products. Biochim. Biophys. Acta, 2004, 1689(2), 91-102.
[http://dx.doi.org/10.1016/j.bbadis.2004.02.008] [PMID: 15196590]
[46]
Sun, M.; Zigman, S. An improved spectrophotometric assay for superoxide dismutase based on epinephrine autoxidation. Anal. Biochem., 1978, 90(1), 81-89.
[http://dx.doi.org/10.1016/0003-2697(78)90010-6] [PMID: 727489]
[47]
Beers, R.F., Jr; Sizer, I.W. A spectrophotometric method for measuring the breakdown of hydrogen peroxide by catalase. J. Biol. Chem., 1952, 195(1), 133-140.
[http://dx.doi.org/10.1016/S0021-9258(19)50881-X] [PMID: 14938361]
[48]
Hu, M.L.; Louie, S.; Cross, C.E.; Motchnik, P.; Halliwell, B. Antioxidant protection against hypochlorous acid in human plasma. J. Lab. Clin. Med., 1993, 121(2), 257-262.
[PMID: 8381845]
[49]
Erel, O. A novel automated direct measurement method for total antioxidant capacity using a new generation, more stable ABTS radical cation. Clin. Biochem., 2004, 37(4), 277-285.
[http://dx.doi.org/10.1016/j.clinbiochem.2003.11.015] [PMID: 15003729]
[50]
Erel, O. A new automated colorimetric method for measuring total oxidant status. Clin. Biochem., 2005, 38(12), 1103-1111.
[http://dx.doi.org/10.1016/j.clinbiochem.2005.08.008] [PMID: 16214125]
[51]
Singh, R.; Kumar, S.; Rana, A.C.; Sharma, N. Different models of hepatotoxicity and related liver diseases: a review. Int. Res. J Pharm., 2012, 3(7), 86-95.
[52]
Singh, A.; Bhat, T.K.; Sharma, O.P. Clinical biochemistry of hepatotoxicity. J. Clin. Toxicol., 2011, 4(1), 1-9.
[http://dx.doi.org/10.4172/2161-0495.S4-001]
[53]
Shin, R-H.; Ri, H-C.; Ri, J-H.; Ri, H-C.; Ri, A-J. Effect of lesimarin against thioacetamide-induced liver cirrhosis in rat. Braz. J. Pharm. Sci., 2019, 55, e17821.
[http://dx.doi.org/10.1590/s2175-97902019000217821]
[54]
Chen, I.S.; Chen, Y.C.; Chou, C.H.; Chuang, R.F.; Sheen, L.Y.; Chiu, C.H. Hepatoprotection of silymarin against thioacetamide-induced chronic liver fibrosis. J. Sci. Food Agric., 2012, 92(7), 1441-1447.
[http://dx.doi.org/10.1002/jsfa.4723] [PMID: 22102319]
[55]
Sukalingam, K.; Ganesan, K.; Xu, B. Protective effect of aqueous extract from the leaves of justicia tranquebariesis against thioacetamide-induced oxidative stress and hepatic fibrosis in rats. Antioxidants, 2018, 7(7), 78.
[http://dx.doi.org/10.3390/antiox7070078] [PMID: 29932107]
[56]
Reuben, A. Hy’s law. Hepatology, 2004, 39(2), 574-578.
[http://dx.doi.org/10.1002/hep.20081] [PMID: 14768020]
[57]
Wang, Z.; Yao, T.; Pini, M.; Zhou, Z.; Fantuzzi, G.; Song, Z. Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease. Am. J. Physiol. Gastrointest. Liver Physiol., 2010, 298(5), G634-G642.
[http://dx.doi.org/10.1152/ajpgi.00249.2009] [PMID: 20203061]
[58]
Khodayar, M.J.; Kalantari, H.; Khorsandi, L.; Rashno, M.; Zeidooni, L. Upregulation of Nrf2-related cytoprotective genes expression by acetaminophen-induced acute hepatotoxicity in mice and the protective role of betaine. Hum. Exp. Toxicol., 2020, 39(7), 948-959.
[http://dx.doi.org/10.1177/0960327120905962] [PMID: 32081044]
[59]
Xie, J.; Yang, L.; Tian, L.; Li, W.; Yang, L.; Li, L. Macrophage migration inhibitor factor upregulates MCP-1 expression in an autocrine manner in hepatocytes during acute mouse liver injury. Sci. Rep., 2016, 6, 27665.
[http://dx.doi.org/10.1038/srep27665] [PMID: 27273604]
[60]
Abdel-Daim, M.M.; Abdellatief, S.A.; Abdellatief, S.A. Attenuating effects of caffeic acid phenethyl ester and betaine on abamectin-induced hepatotoxicity and nephrotoxicity. Environ. Sci. Pollut. Res. Int., 2018, 25(16), 15909-15917.
[http://dx.doi.org/10.1007/s11356-018-1786-8] [PMID: 29589235]
[61]
Radosavljevic, T.S.; Mladenovic, D.R.; Ninkovic, M.B.; Vucevic, D.B.; Boricic, I.V.; Jesic-Vukicevic, R.S.; Sljivancanin, T.; Lopicic, S.N.; Todorovic, V.N. Oxidative stress in rat liver during acute cadmium and ethanol intoxication. J. Serb. Chem. Soc., 2012, 77(2), 159-176.
[http://dx.doi.org/10.2298/JSC110330174R]
[62]
Ahn, M.; Park, J.S.; Chae, S.; Kim, S.; Moon, C.; Hyun, J.W.; Shin, T. Hepatoprotective effects of Lycium chinense Miller fruit and its constituent betaine in CCl4-induced hepatic damage in rats. Acta Histochem., 2014, 116(6), 1104-1112.
[http://dx.doi.org/10.1016/j.acthis.2014.05.004] [PMID: 24998029]
[63]
Zhang, M.; Zhang, H.; Li, H.; Lai, F.; Li, X.; Tang, Y.; Min, T.; Wu, H. Antioxidant mechanism of betaine without free radical scavenging ability. J. Agric. Food Chem., 2016, 64(42), 7921-7930.
[http://dx.doi.org/10.1021/acs.jafc.6b03592] [PMID: 27677203]
[64]
Zhao, G.; He, F.; Wu, C.; Li, P.; Li, N.; Deng, J.; Zhu, G.; Ren, W.; Peng, Y. Betaine in inflammation: mechanistic aspects and applications. Front. Immunol., 2018, 24(9), 1070.
[http://dx.doi.org/10.3389/fimmu.2018.01070] [PMID: 29881379 ]
[65]
Nguyen, M.T.; Lue, H.; Kleemann, R.; Thiele, M.; Tolle, G.; Finkelmeier, D.; Wagner, E.; Braun, A.; Bernhagen, J. The cytokine macrophage migration inhibitory factor reduces pro-oxidative stress-induced apoptosis. J. Immunol., 2003, 170(6), 3337-3347.
[http://dx.doi.org/10.4049/jimmunol.170.6.3337] [PMID: 12626594]
[66]
Israelson, A.; Ditsworth, D.; Sun, S.; Song, S.; Liang, J.; Hruska-Plochan, M.; McAlonis-Downes, M.; Abu-Hamad, S.; Zoltsman, G.; Shani, T.; Maldonado, M.; Bui, A.; Navarro, M.; Zhou, H.; Marsala, M.; Kaspar, B.K.; Da Cruz, S.; Cleveland, D.W. Macrophage migration inhibitory factor as a chaperone inhibiting accumulation of misfolded SOD1. Neuron, 2015, 86(1), 218-232.
[http://dx.doi.org/10.1016/j.neuron.2015.02.034] [PMID: 25801706]
[67]
Ko, J.A.; Sotani, Y.; Ibrahim, D.G.; Kiuchi, Y. Role of macrophage migration inhibitory factor (MIF) in the effects of oxidative stress on human retinal pigment epithelial cells. Cell Biochem. Funct., 2017, 35(7), 426-432.
[http://dx.doi.org/10.1002/cbf.3292] [PMID: 28906008]
[68]
Hu, Y.; Xia, W.; Hou, M. Macrophage migration inhibitory factor serves a pivotal role in the regulation of radiation-induced cardiac senescencethrough rebalancing the microRNA-34a/sirtuin 1 signaling pathway. Int. J. Mol. Med., 2018, 42(5), 2849-2858.
[http://dx.doi.org/10.3892/ijmm.2018.3838] [PMID: 30226567]
[69]
Ruze, A.; Chen, B.D.; Liu, F.; Chen, X.C.; Gai, M.T.; Li, X.M.; Ma, Y.T.; Du, X.J.; Yang, Y.N.; Gao, X.M. Macrophage migration inhibitory factor plays an essential role in ischemic preconditioning-mediated cardioprotection. Clin. Sci. (Lond.), 2019, 133(5), 665-680.
[http://dx.doi.org/10.1042/CS20181013] [PMID: 30804219]
[70]
Li, J.H.; Tang, Y.; Lv, J.; Wang, X.H.; Yang, H.; Tang, P.M.K.; Huang, X.R.; He, Z.J.; Zhou, Z.J.; Huang, Q.Y.; Klug, J.; Meinhardt, A.; Fingerle-Rowson, G.; Xu, A.P.; Zheng, Z.H.; Lan, H.Y. Macrophage migration inhibitory factor promotes renal injury induced by ischemic reperfusion. J. Cell. Mol. Med., 2019, 23(6), 3867-3877.
[http://dx.doi.org/10.1111/jcmm.14234] [PMID: 30968541]
[71]
Merk, M.; Mitchell, R.A.; Endres, S.; Bucala, R. D-dopachrome tautomerase (D-DT or MIF-2): doubling the MIF cytokine family. Cytokine, 2012, 59(1), 10-17.
[http://dx.doi.org/10.1016/j.cyto.2012.03.014] [PMID: 22507380]
[72]
Kleemann, R.; Kapurniotu, A.; Frank, R.W.; Gessner, A.; Mischke, R.; Flieger, O.; Jüttner, S.; Brunner, H.; Bernhagen, J. Disulfide analysis reveals a role for macrophage migration inhibitory factor (MIF) as thiol-protein oxidoreductase. J. Mol. Biol., 1998, 280(1), 85-102.
[http://dx.doi.org/10.1006/jmbi.1998.1864] [PMID: 9653033]
[73]
Schinagl, A.; Kerschbaumer, R.J.; Sabarth, N.; Douillard, P.; Scholz, P.; Voelkel, D.; Hollerweger, J.C.; Goettig, P.; Brandstetter, H.; Scheiflinger, F.; Thiele, M. Role of the cysteine 81 residue of macrophage migration inhibitory factor as a molecular redox switch. Biochemistry, 2018, 57(9), 1523-1532.
[http://dx.doi.org/10.1021/acs.biochem.7b01156] [PMID: 29412660]
[74]
Yukitake, H.; Takizawa, M.; Kimura, H. Macrophage migration inhibitory factor as an emerging drug target to regulate antioxidant response element system. Oxid. Med. Cell. Longev., 2017, 2017, 8584930.
[http://dx.doi.org/10.1155/2017/8584930] [PMID: 28191280]
[75]
Riad, A.; Jäger, S.; Sobirey, M.; Escher, F.; Yaulema-Riss, A.; Westermann, D.; Karatas, A.; Heimesaat, M.M.; Bereswill, S.; Dragun, D.; Pauschinger, M.; Schultheiss, H.P.; Tschöpe, C. Toll-like receptor-4 modulates survival by induction of left ventricular remodeling after myocardial infarction in mice. J. Immunol., 2008, 180(10), 6954-6961.
[http://dx.doi.org/10.4049/jimmunol.180.10.6954] [PMID: 18453617]
[76]
Kharbanda, K.K.; Mailliard, M.E.; Baldwin, C.R.; Beckenhauer, H.C.; Sorrell, M.F.; Tuma, D.J. Betaine attenuates alcoholic steatosis by restoring phosphatidylcholine generation via the phosphatidylethanolamine methyltransferase pathway. J. Hepatol., 2007, 46(2), 314-321.
[http://dx.doi.org/10.1016/j.jhep.2006.08.024] [PMID: 17156888]
[77]
Yi, E-Y.; Kim, Y-J. Betaine inhibits in vitro and in vivo angiogenesis through suppression of the NF-κB and Akt signaling pathways. Int. J. Oncol., 2012, 41(5), 1879-1885.
[http://dx.doi.org/10.3892/ijo.2012.1616] [PMID: 22940742]
[78]
Jacobs, R.L.; van der Veen, J.N.; Vance, D.E. Finding the balance: the role of S-adenosylmethionine and phosphatidylcholine metabolism in development of nonalcoholic fatty liver disease. Hepatology, 2013, 58(4), 1207-1209.
[http://dx.doi.org/10.1002/hep.26499] [PMID: 23703836]
[79]
Kim, S.K.; Kim, Y.C. Effects of betaine supplementation on hepatic metabolism of sulfur-containing amino acids in mice. J. Hepatol., 2005, 42(6), 907-913.
[http://dx.doi.org/10.1016/j.jhep.2005.01.017] [PMID: 15885362]
[80]
Jacobs, R.L.; van der Veen, J.N.; Vance, D.E. Finding the balance: the role of S-adenosylmethionine and phosphatidylcholine metabolism in development of nonalcoholic fatty liver disease. Hepatology, 2013, 58(4), 1207-1209.
[http://dx.doi.org/10.1002/hep.26499] [PMID: 23703836]
[81]
Okada, T.; Kawakami, S.; Nakamura, Y.; Han, K-H.; Ohba, K.; Aritsuka, T.; Uchino, H.; Shimada, K.; Sekikawa, M.; Ishii, H.; Fukushima, M. Amelioration of D-galactosamine-induced acute liver injury in rats by dietary supplementation with betaine derived from sugar beet molasses. Biosci. Biotechnol. Biochem., 2011, 75(7), 1335-1341.
[http://dx.doi.org/10.1271/bbb.110105] [PMID: 21737928]
[82]
Yeung, J.H.K.; Or, P.M. Effects of polysaccharide peptides from COV-1 strain of Coriolus versicolor on glutathione and glutathione-related enzymes in the mouse. Food Chem. Toxicol., 2007, 45(6), 953-961.
[http://dx.doi.org/10.1016/j.fct.2006.12.005] [PMID: 17240508]
[83]
Go, E.K.; Jung, K.J.; Kim, J.M.; Lim, H.; Lim, H.K.; Yu, B.P.; Chung, H.Y. Betaine modulates age-related NF-kappaB by thiol-enhancing action. Biol. Pharm. Bull., 2007, 30(12), 2244-2249.
[http://dx.doi.org/10.1248/bpb.30.2244] [PMID: 18057706]
[84]
Kanbak, G.; Akyüz, F.; Inal, M. Preventive effect of betaine on ethanol-induced membrane lipid composition and membrane ATPases. Arch. Toxicol., 2001, 75(1), 59-61.
[http://dx.doi.org/10.1007/s002040000179] [PMID: 11357522]
[85]
Alirezaei, M.; Khoshdel, Z.; Dezfoulian, O.; Rashidipour, M.; Taghadosi, V. Beneficial antioxidant properties of betaine against oxidative stress mediated by levodopa/benserazide in the brain of rats. J. Physiol. Sci., 2015, 65(3), 243-252.
[http://dx.doi.org/10.1007/s12576-015-0360-0] [PMID: 25665954]
[86]
Merk, M.; Baugh, J.; Zierow, S.; Leng, L.; Pal, U.; Lee, S.J.; Ebert, A.D.; Mizue, Y.; Trent, J.O.; Mitchell, R.; Nickel, W.; Kavathas, P.B.; Bernhagen, J.; Bucala, R. The Golgi-associated protein p115 mediates the secretion of macrophage migration inhibitory factor. J. Immunol., 2009, 182(11), 6896-6906.
[http://dx.doi.org/10.4049/jimmunol.0803710] [PMID: 19454686]
[87]
Ping, Z.; Peng, Y.; Lang, H.; Xinyong, C.; Zhiyi, Z.; Xiaocheng, W.; Hong, Z.; Liang, S. Oxidative stress in radiation-induced cardiotoxicity. Oxid. Med. Cell. Longev., 2020, 2020, 3579143.
[http://dx.doi.org/10.1155/2020/3579143] [PMID: 32190171]
[88]
Wheelhouse, N.M.; Dowidar, N.; Dejong, C.H.; Garden, O.J.; Powell, J.J.; Barber, M.D.; Sangster, K.; Maingay, J.P.; Ross, J.A. The effects of macrophage migratory inhibitory factor on acute-phase protein production in primary human hepatocytes. Int. J. Mol. Med., 2006, 18(5), 957-961.
[http://dx.doi.org/10.3892/ijmm.18.5.957] [PMID: 17016627]
[89]
Kozaci, L.D.; Sari, I.; Alacacioglu, A.; Akar, S.; Akkoc, N. Evaluation of inflammation and oxidative stress in ankylosing spondylitis: a role for macrophage migration inhibitory factor. Mod. Rheumatol., 2010, 20(1), 34-39.
[http://dx.doi.org/10.3109/s10165-009-0230-9] [PMID: 19787418]
[90]
Park, M.C.; Kwon, O.C.; Lee, S.W.; Song, J.J.; Park, Y.B. MiR-451 suppresses inflammatory responses in ankylosing spondylitis by targeting macrophage migration inhibitory factor. Clin. Exp. Rheumatol., 2020, 38(2), 275-281.
[PMID: 31287414]
[91]
Eissa, L.A.; Kenawy, H.I.; El-Karef, A.; Elsherbiny, N.M.; El-Mihi, K.A. Antioxidant and anti-inflammatory activities of berberine attenuate hepatic fibrosis induced by thioacetamide injection in rats. Chem. Biol. Interact., 2018, 294, 91-100.
[http://dx.doi.org/10.1016/j.cbi.2018.08.016] [PMID: 30138605]
[92]
Wang, J.; Gujar, S.A.; Cova, L.; Michalak, T.I. Bicistronic woodchuck hepatitis virus core and gamma interferon DNA vaccine can protect from hepatitis but does not elicit sterilizing antiviral immunity. J. Virol., 2007, 81(2), 903-916.
[http://dx.doi.org/10.1128/JVI.01537-06] [PMID: 17079319]
[93]
Tan, G.; Song, H.; Xu, F.; Cheng, G. When hepatitis B virus meets interferons. Front. Microbiol., 2018, 9, 1611.
[http://dx.doi.org/10.3389/fmicb.2018.01611] [PMID: 30072974]
[94]
Calandra, T.; Bucala, R. Macrophage migration inhibitory factor (MIF): a glucocorticoid counter-regulator within the immune system. Crit. Rev. Immunol., 2017, 37(2-6), 359-370.
[http://dx.doi.org/10.1615/CritRevImmunol.v37.i2-6.90] [PMID: 29773026]
[95]
Ruiz-Rosado, J.D.; Olguín, J.E.; Juárez-Avelar, I.; Saavedra, R.; Terrazas, L.I. Partida-Sánchez, Robledo-Avila, F.H.; Vazquez-Mendoza, A.; Fernández, J.; Satoskar, A.R.; Rodriguez-Sosa, M. MIF promotes classical activation and conversion of inflammatory Ly6c(high) monocytes into TipDCs during murine toxoplasmosis. Mediators Inflamm., 2016, 2016, 9101762.
[http://dx.doi.org/10.1155/2016/9101762] [PMID: 27057101]
[96]
Wang, Y.; Yu, W.; Shen, C.; Wang, W.; Zhang, L.; Liu, F.; Sun, H.; Zhao, Y.; Che, H.; Zhao, C. Predictive value of serum IFN-γ inducible protein-10 and IFN-γ/IL-4 ratio for liver fibrosis progression in CHB patients. Sci. Rep., 2017, 7, 40404.
[http://dx.doi.org/10.1038/srep40404] [PMID: 28067328]
[97]
Leng, L.; Metz, C.N.; Fang, Y.; Xu, J.; Donnelly, S.; Baugh, J.; Delohery, T.; Chen, Y.; Mitchell, R.A.; Bucala, R. MIF signal transduction initiated by binding to CD74. J. Exp. Med., 2003, 197(11), 1467-1476.
[http://dx.doi.org/10.1084/jem.20030286] [PMID: 12782713]
[98]
van der Vorst, E.P.C.; Döring, Y.; Weber, C. Chemokines and their receptors in Atherosclerosis. J. Mol. Med. (Berl.), 2015, 93(9), 963-971.
[http://dx.doi.org/10.1007/s00109-015-1317-8] [PMID: 26175090]
[99]
Barnes, M.A.; McMullen, M.R.; Roychowdhury, S.; Pisano, S.G.; Liu, X.; Stavitsky, A.B.; Bucala, R.; Nagy, L.E. Macrophage migration inhibitory factor contributes to ethanol-induced liver injury by mediating cell injury, steatohepatitis, and steatosis. Hepatology, 2013, 57(5), 1980-1991.
[http://dx.doi.org/10.1002/hep.26169] [PMID: 23174952]
[100]
Qin, D.; Jiang, Y.; Jin, X. Effect of macrophage migration inhibitory factor on inflammatory cytokines and fibrogenic gene expression in human RPE cells. Mol. Med. Rep., 2019, 20(1), 830-836.
[http://dx.doi.org/10.3892/mmr.2019.10277] [PMID: 31180524]
[101]
Poulsen, K.L.; McMullen, M.R.; Huang, E.; Kibler, C.D.; Sheehan, M.M.; Leng, L.; Bucala, R.; Nagy, L.E. Novel role of macrophage migration inhibitory factor in upstream control of the unfolded protein response after ethanol feeding in mice. Alcohol. Clin. Exp. Res., 2019, 43(7), 1439-1451.
[http://dx.doi.org/10.1111/acer.14065] [PMID: 31009094]
[102]
Poulsen, K.; Mcmullen, M.; Sheehan, M.; Leng, L.; Bucala, R.; Nagy, L. Protection from Gao-Binge induced liver injury in Mif-/- Mice is associated with decreased ER stress. J. Hepatol., 2018, 68, S47-S48.
[http://dx.doi.org/10.1016/S0168-8278(18)30313-1]
[103]
Lang, T.; Lee, J.P.W.; Elgass, K.; Pinar, A.A.; Tate, M.D.; Aitken, E.H.; Fan, H.; Creed, S.J.; Deen, N.S.; Traore, D.A.K.; Mueller, I.; Stanisic, D.; Baiwog, F.S.; Skene, C.; Wilce, M.C.J.; Mansell, A.; Morand, E.F.; Harris, J. Macrophage migration inhibitory factor is required for NLRP3 inflammasome activation. Nat. Commun., 2018, 9(1), 2223.
[http://dx.doi.org/10.1038/s41467-018-04581-2] [PMID: 29884801]
[104]
Tsiomita, S.; Georgopoulou, U.; Doumba, P.P.; Koskinas, J.; Adamidis, K.; Papaloukas, C.; Thyphronitis, G. Evaluation of alternative serum biomarkers to monitor the progression of chronic HBV and HCV infection. Infect. Genet. Evol., 2018, 58, 17-22.
[http://dx.doi.org/10.1016/j.meegid.2017.12.002] [PMID: 29221787]
[105]
Rodriguez-Sosa, M.; Cabellos-Avelar, T.; Sanchez-Zamora, Y.; Juárez-Avelar, I.; García-Reyes, E.; Lira-León, A.; Benítez-Flores, J.D.C.; Pacheco-Fernández, T.; Hiriart, M.; Gutiérrez-Cirlos, E.B. Proinflammatory cytokine MIF plays a role in the pathogenesis of type-2 diabetes mellitus, but does not affect hepatic mitochondrial function. Cytokine, 2017, 99, 214-224.
[http://dx.doi.org/10.1016/j.cyto.2017.07.012] [PMID: 28780379]
[106]
Sanchez-Zamora, Y.; Terrazas, L.I.; Vilches-Flores, A.; Leal, E.; Juárez, I.; Whitacre, C.; Kithcart, A.; Pruitt, J.; Sielecki, T.; Satoskar, A.R.; Rodriguez-Sosa, M. Macrophage migration inhibitory factor is a therapeutic target in treatment of non-insulin-dependent diabetes mellitus. FASEB J., 2010, 24(7), 2583-2590.
[http://dx.doi.org/10.1096/fj.09-147066] [PMID: 20203087]
[107]
Li, Y.-H.; Wen, K.; Zhu, L.-L.; Lv, S.-K.; Cao, Q.; Li, Q.; Deng, L.; Chen, T.; Wang, X.; Deng, K.-Y.; Wang, L.-F.; Xin, H.-B. Tautomerase activity-lacking of the macrophage migration inhibitory factor alleviates the inflammation and insulin tolerance in high fat diet-induced obese mice. Front. Endocrinol. (Lausanne), 2020, 11, 134.
[http://dx.doi.org/10.3389/fendo.2020.00134] [PMID: 32265835]
[108]
Gligorovska, L.; Bursać, B.; Kovačević, S.; Veličković, N.; Matić, G.; Djordjevic, A. Mif deficiency promotes adiposity in fructose-fed mice. J. Endocrinol., 2019, 240(2), 133-145.
[http://dx.doi.org/10.1530/JOE-18-0333] [PMID: 30400058]
[109]
Ju, C.; Mandrekar, P. Macrophages and alcohol-related liver inflammation. Alcohol Res., 2015, 37(2), 251-262.
[PMID: 26717583]
[110]
Jankauskas, S.S.; Wong, D.W.L.; Bucala, R.; Djudjaj, S.; Boor, P. Evolving complexity of MIF signaling. Cell. Signal., 2019, 57, 76-88.
[http://dx.doi.org/10.1016/j.cellsig.2019.01.006] [PMID: 30682543]
[111]
Barnes, M.A.; McMullen, M.R.; Roychowdhury, S.; Madhun, N.Z.; Niese, K.; Olman, M.A.; Stavitsky, A.B.; Bucala, R.; Nagy, L.E. Macrophage migration inhibitory factor is required for recruitment of scar-associated macrophages during liver fibrosis. J. Leukoc. Biol., 2015, 97(1), 161-169.
[http://dx.doi.org/10.1189/jlb.3A0614-280R] [PMID: 25398607]
[112]
Heinrichs, D.; Knauel, M.; Offermanns, C.; Berres, M.-L.; Nellen, A.; Leng, L.; Schmitz, P.; Bucala, R.; Trautwein, C.; Weber, C.; Bernhagen, J.; Wasmuth, H.E. Macrophage migration inhibitory factor (MIF) exerts antifibrotic effects in experimental liver fibrosis via CD74. Proc. Natl. Acad. Sci. USA, 2011, 108(42), 17444-17449.
[http://dx.doi.org/10.1073/pnas.1107023108] [PMID: 21969590]
[113]
Thuy, T.T.; Kawada, N.; Kawada, N. Antifibrotic role of macrophage migration inhibitory factor: discovery of an unexpected function. Hepatology, 2012, 55(4), 1295-1297.
[http://dx.doi.org/10.1002/hep.25605] [PMID: 22461077]
[114]
Kim, M.J.; Kim, W.S.; Kim, D.O.; Byun, J.E.; Huy, H.; Lee, S.Y.; Song, H.Y.; Park, Y.J.; Kim, T.D.; Yoon, S.R.; Choi, E.J.; Ha, H.; Jung, H.; Choi, I. Macrophage migration inhibitory factor interacts with thioredoxin-interacting protein and induces NF-κB activity. Cell. Signal., 2017, 34, 110-120.
[http://dx.doi.org/10.1016/j.cellsig.2017.03.007] [PMID: 28323005]
[115]
Shin, M.S.; Kang, Y.; Wahl, E.R.; Park, H.J.; Lazova, R.; Leng, L.; Mamula, M.; Krishnaswamy, S.; Bucala, R.; Kang, I. Macrophage migration inhibitory factor regulates u1 small nuclear RNP immune complex-mediated activation of the NLRP3 inflammasome. Arthritis Rheumatol., 2019, 71(1), 109-120.
[http://dx.doi.org/10.1002/art.40672] [PMID: 30009530]
[116]
Miller, E.J.; Li, J.; Leng, L.; McDonald, C.; Atsumi, T.; Bucala, R.; Young, L.H. Macrophage migration inhibitory factor stimulates AMP-activated protein kinase in the ischaemic heart. Nature, 2008, 451(7178), 578-582.
[http://dx.doi.org/10.1038/nature06504] [PMID: 18235500]
[117]
Zhang, L.; Qi, Y.; ALuo, Z.; Liu, S.; Zhang, Z.; Zhou, L. Betaine increases mitochondrial content and improves hepatic lipid metabolism. Food Funct., 2019, 10(1), 216-223.
[http://dx.doi.org/10.1039/C8FO02004C] [PMID: 30534761]
[118]
Jung Kim, M. Betaine enhances the cellular survival via mitochondrial fusion and fission factors, MFN2 and DRP1. Anim Cells Syst (Seoul), 2018, 22(5), 289-298.
[http://dx.doi.org/10.1080/19768354.2018.1512523] [PMID: 30460110]
[119]
Sivanesan, S.; Taylor, A.; Zhang, J.; Bakovic, M. Betaine and choline improve lipid homeostasis in obesity by participation in mitochondrial oxidative demethylation. Front. Nutr., 2018, 5, 61.
[http://dx.doi.org/10.3389/fnut.2018.00061] [PMID: 30042948]
[120]
Meng, X.; Li, Y.; Li, S.; Gan, R-Y.; Li, H-B. Natural products for prevention and treatment of chemical-induced liver injuries. Compr. Rev. Food Sci. Food Saf., 2018, 17(2), 472-495.
[http://dx.doi.org/10.1111/1541-4337.12335] [PMID: 33350084]

Rights & Permissions Print Cite
Article Metrics
38
1
© 2024 Bentham Science Publishers | Privacy Policy