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RETRACTED ARTICLE: Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats

Laboratory Animal Research volume 34, pages 49–57 (2018)Cite this article

This article was retracted on 11 June 2020

This article has been updated

Abstract

Hangover is characterized by a number of unpleasant physical and mental symptoms that occur after heavy alcohol drinking. In addition, consistently excessive alcohol intake is considered as a major reason causes liver disease. The present study investigated the in vivo effects of DA-5513 (Morning careê Kang Hwang) on biological parameters relevant to hangover relief and alcoholic fatty liver. Blood alcohol and acetaldehyde concentrations were determined in rats administered a single dose of alcohol and treated with DA-5513 or commercially available hangover relief beverages (Yeomyungê and Ukonê). The effects of DA-5513 on alcoholic fatty liver were also determined in rats fed alcohol-containing Lieber-DeCarli diets for 4 weeks. Serum liver function markers (aspartate and alanine aminotransferase activities) and serum/liver lipid levels were assessed. Blood alcohol and acetaldehyde concentrations were lower in the groups treated with DA-5513 or Yeomyungê, as compared with control rats. However, Ukonê did not produce any significant effects on these parameters. Treatment with DA-5513 significantly reduced serum aspartate and alanine aminotransferase activities and markedly reduced serum cholesterol and triglyceride levels, as compared with control rats. Histological observations using Oil Red O staining found that DA-5513 delayed the development of alcoholic fatty liver by reversing hepatic fat accumulation. These findings suggest that DA-5513 could have a beneficial effect on alcohol-induced hangovers and has the potential to ameliorate alcoholic fatty liver.

Change history

  • 11 June 2020

    An amendment to this paper has been published and can be accessed via the original article.

References

  1. Rehm J, Mathers C, Popova S, Thavorncharoensap M, Teerawattananon Y, Patra J. Global burden of disease and injury and economic cost attributable to alcohol use and alcohol-use disorders. Lancet 2009; 373(9682): 2223–2233.

    Article  PubMed  Google Scholar 

  2. Wiese J, McPherson S, Odden MC, Shlipak MG. Effect of Opuntia ficus indica on symptoms of the alcohol hangover. Arch Intern Med 2004; 164(12): 1334–1340.

    Article  PubMed  Google Scholar 

  3. Swift R, Davidson D. Alcohol hangover: mechanisms and mediators. Alcohol Health Res World 1998; 22(1): 54–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Lieber CS. Alcoholic fatty liver: its pathogenesis and mechanism of progression to inflammation and fibrosis. Alcohol 2004; 34(1): 9–19.

    Article  CAS  PubMed  Google Scholar 

  5. Altamirano J, Bataller R. Alcoholic liver disease: pathogenesis and new targets for therapy. Nat Rev Gastroenterol Hepatol 2011; 8(9): 491–501.

    Article  CAS  PubMed  Google Scholar 

  6. Purohit V, Gao B, Song BJ. Molecular mechanisms of alcoholic fatty liver. Alcohol Clin Exp Res 2009; 33(2): 191–205.

    Article  CAS  PubMed  Google Scholar 

  7. Lafontan M, Girard J. Impact of visceral adipose tissue on liver metabolism: Part I: Heterogeneity of adipose tissue and functional properties of visceral adipose tissue. Diabetes Metab 2008; 34(4): 317–327.

    Article  CAS  PubMed  Google Scholar 

  8. Wree A, Kahraman A, Gerken G, Canbay A. Obesity affects the liver-the link between adipocytes and hepatocytes. Digestion 2011; 83(1-2): 124–133.

    Article  PubMed  Google Scholar 

  9. Zhong W, Zhao Y, Tang Y, Wei X, Shi X, Sun W, Sun X, Yin X, Sun X, Kim S, McClain CJ, Zhang X, Zhou Z. Chronic alcohol exposure stimulates adipose tissue lipolysis in mice: role of reverse triglyceride transport in the pathogenesis of alcoholic steatosis. Am J Pathol 2012; 180(3): 998–1007.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Addolorato G, Capristo E, Greco AV, Stefanini GF, Gasbarrini G. Influence of chronic alcohol abuse on body weight and energy metabolism: is excess ethanol consumption a risk factor for obesity or malnutrition? J Intern Med 1998; 244(5): 387–395.

    Article  CAS  PubMed  Google Scholar 

  11. Li Y, Wong K, Giles A, Jiang J, Lee JW, Adams AC, Kharitonenkov A, Yang Q, Gao B, Guarente L, Zang M. Hepatic SIRT1 attenuates hepatic steatosis and controls energy balance in mice by inducing fibroblast growth factor 21. Gastroenterology 2014; 146(2): 539–549. e7.

    Article  CAS  PubMed  Google Scholar 

  12. Suter PM, Schutz Y, Jequier E. The effect of ethanol on fat storage in healthy subjects. N Engl J Med 1992; 326(15): 983–987.

    Article  CAS  PubMed  Google Scholar 

  13. Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 2010; 52(2): 774–788.

    Article  PubMed  CAS  Google Scholar 

  14. Pulido-Moran M, Moreno-Fernandez J, Ramirez-Tortosa C, Ramirez-Tortosa M. Curcumin and health. Molecules 2016; 21(3): 264.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  15. You Y, Duan X, Wei X, Su X, Zhao M, Sun J, Ruenroengklin N, Jiang Y. Identification of major phenolic compounds of Chinese water chestnut and their antioxidant activity. Molecules 2007; 12(4): 842–852.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Vargas-Mendoza N, Madrigal-Santillán E, Morales-González Á, Esquivel-Soto J, Esquivel-Chirino C, García-Luna y González-Rubio M, Gayosso-de-Lucio JA, Morales-González JA. Hepatoprotective effect of silymarin. World J Hepatol 2014; 6(3): 144–149.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Chang BY, Lee DS, Lee JK, Kim YC, Cho HK, Kim SY. Protective activity of kudzu (Pueraria thunbergiana) vine on chemically-induced hepatotoxicity: in vitro and in vivo studies. BMC Complement Altern Med 2016; 16: 39.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Mattei R, Dias RF, Espínola EB, Carlini EA, Barros SB. Guarana (Paullinia cupana): toxic behavioral effects in laboratory animals and antioxidants activity in vitro. J Ethnopharmacol 1998; 60(2): 111–116.

    Article  CAS  PubMed  Google Scholar 

  19. Cheng N, Du B, Wang Y, Gao H, Cao W, Zheng J, Feng F. Antioxidant properties of jujube honey and its protective effects against chronic alcohol-induced liver damage in mice. Food Funct 2014; 5(5): 900–908.

    Article  CAS  PubMed  Google Scholar 

  20. Kober H, Tatsch E, Torbitz VD, Cargnin LP, Sangoi MB, Bochi G V, da Silva AR, Barbisan F, Ribeiro EE, da Cruz IB, Moresco RN. Genoprotective and hepatoprotective effects of Guarana (Paullinia cupana Mart. var. sorbilis) on CCl4-induced liver damage in rats. Drug Chem Toxicol 2016; 39(1): 48–52.

    Article  CAS  PubMed  Google Scholar 

  21. Kim CI, Leo MA, Lowe N, Lieber CS. Differential effects of retinoids and chronic ethanol consumption on membranes in rats. J Nutr 1988; 118(9): 1097–1103.

    Article  CAS  PubMed  Google Scholar 

  22. Yin HQ, Lee BH. Temporal changes in the hepatic fatty liver in mice receiving standard Lieber-DeCarli diet. Toxicological Research 2008; 24(2): 113–117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Bligh EG, Dyer WJ. A rapid method of total lipid extraction and purification. Canadian journal of biochemistry and physiology 1959; 37(8): 911–917.

    Article  CAS  PubMed  Google Scholar 

  24. Levene AP, Kudo H, Thursz MR, Anstee QM, Goldin RD. Is oil red-O staining and digital image analysis the gold standard for quantifying steatosis in the liver? Hepatology 2010; 51(5): 1859.

    Article  PubMed  Google Scholar 

  25. Kucherenko MM, Marrone AK, Rishko VM, Yatsenko AS, Klepzig A, Shcherbata HR. Paraffin-embedded and frozen sections of drosophila adult muscles. J Vis Exp 2010; (46): 2438.

    Google Scholar 

  26. Fakhoury-Sayegh N, Trak-Smayra V, Khazzaka A, Esseily F, Obeid O, Lahoud-Zouein M, Younes H. Characteristics of nonalcoholic fatty liver disease induced in wistar rats following four different diets. Nutr Res Pract 2015; 9(4): 350–357.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Yogalakshmi B, Sreeja S, Geetha R, Radika MK, Anuradha C V. Grape Seed Proanthocyanidin Rescues Rats from Steatosis: A Comparative and Combination Study with Metformin. J Lipids 2013; 2013: 153897.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Lieber CS. Alcohol: its metabolism and interaction with nutrients. Annual review of nutrition 2000; 20(1): 395–430.

    Article  CAS  PubMed  Google Scholar 

  29. Lu Y, Cederbaum AI. CYP2E1 and oxidative liver injury by alcohol. Free Radic Biol Med 2008; 44(5): 723–738.

    Article  CAS  PubMed  Google Scholar 

  30. Guengerich FP, Beaune PH, Umbenhauer DR, Churchill PF, Bork RW, Dannan GA, Knodell R G, Lloyd RS, Martin M V. Cytochrome P-450 enzymes involved in genetic polymorphism of drug oxidation in humans. Biochem Soc Trans 1987; 15(4): 576–578.

    Article  CAS  PubMed  Google Scholar 

  31. Stewart S, Jones D, Day CP. Alcoholic liver disease: new insights into mechanisms and preventative strategies. Trends Mol Med 2001; 7(9): 408–413.

    Article  CAS  PubMed  Google Scholar 

  32. Ceni E, Mello T, Galli A. Pathogenesis of alcoholic liver disease: role of oxidative metabolism. World J Gastroenterol 2014; 20(47): 17756–17772.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Lakshman MR. Some novel insights into the pathogenesis of alcoholic steatosis. Alcohol 2004; 34(1): 45–48.

    Article  CAS  PubMed  Google Scholar 

  34. Lieber CS, DeCarli LM, Sorrell MF. Experimental methods of ethanol administration. Hepatology 1989; 10(4): 501–510.

    Article  CAS  PubMed  Google Scholar 

  35. Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology 2005; 129(1): 113–121.

    Article  PubMed  Google Scholar 

  36. Hong M, Li S, Tan H Y, Wang N, Tsao SW, Feng Y. Current status of herbal medicines in chronic liver disease therapy: the biological effects, molecular targets and future prospects. Int J Mol Sci 2015; 16(12): 28705–28745.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lee HS, Song J, Kim TM, Joo SS, Park D, Jeon JH, Shin S, Park HK, Lee WK, Ly S Y, Kim MR, Lee DI, Kim YB. Effects of a preparation of combined glutathione-enriched yeast and rice embryo/soybean extracts on ethanol hangover. J Med Food 2009; 12(6): 1359–1367.

    Article  CAS  PubMed  Google Scholar 

  38. Takahashi H, Greenway H, Matsumura H, Tsutsumi N, Nakazono M. Rice alcohol dehydrogenase 1 promotes survival and has a major impact on carbohydrate metabolism in the embryo and endosperm when seeds are germinated in partially oxygenated water. Ann Bot 2014; 113(5): 851–859.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Kiso Y, Suzuki Y, Watanabe N, Oshima Y, Hikino H. Antihepatotoxic principles of Curcuma longa rhizomes. Planta medica 1983; 49(11): 185–187.

    Article  CAS  PubMed  Google Scholar 

  40. Reddy AC, Lokesh BR. Effect of dietary turmeric (Curcuma longa) on iron-induced lipid peroxidation in the rat liver. Food Chem Toxicol 1994; 32(3): 279–283.

    Article  CAS  PubMed  Google Scholar 

  41. Sasaki H, Sunagawa Y, Takahashi K, Imaizumi A, Fukuda H, Hashimoto T, Wada H, Katanasaka Y, Kakeya H, Fujita M, Hasegawa K, Morimoto T. Innovative preparation of curcumin for improved oral bioavailability. Biol Pharm Bull 2011; 34(5): 660–665.

    Article  CAS  PubMed  Google Scholar 

  42. Hamano T, Nishi M, Itoh T, Ebihara S, Watanabe Y. The effect of beverage containing curcuma longa L. extract on the alcohol metabolism of healthy volunteers. Oyo Yakuri (Pharmacometrics) 2007; 72(1-2): 31–38.

    Google Scholar 

  43. Kamal-Eldin A, Frank J, Razdan A, Tengblad S, Basu S, Vessby B. Effects of dietary phenolic compounds on tocopherol, cholesterol, and fatty acids in rats. Lipids 2000; 35(4): 427–435.

    Article  CAS  PubMed  Google Scholar 

  44. Fehér J, Deák G, Müzes G, Láng I, Niederland V, Nékám K, Kárteszi M. Liver-protective action of silymarin therapy in chronic alcoholic liver diseases. Orv Hetil 1989; 130(51): 2723–2727.

    PubMed  Google Scholar 

  45. Ferenci P, Dragosics B, Dittrich H, Frank H, Benda L, Lochs H, Meryn S, Base W, Schneider B. Randomized controlled trial of silymarin treatment in patients with cirrhosis of the liver. J Hepatol 1989; 9(1): 105–113.

    Article  CAS  PubMed  Google Scholar 

  46. Kim YS, Hwang JW, Jang JH, Son S, Seo IB, Jeong JH, Kim EH, Moon SH, Jeon BT, Park PJ. Trapa japonica pericarp extract reduces LPS-induced inflammation in macrophages and acute lung injury in mice. Molecules 2016; 21(3): 392.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  47. Kim YS, Hwang JW, Han YK, Kwon HJ, Hong H, Kim EH, Moon SH, Jeon BT, Park PJ. Antioxidant activity and protective effects of Trapa japonica pericarp extracts against tert-butylhydroperoxide-induced oxidative damage in Chang cells. Food Chem Toxicol 2014; 64: 49–56.

    Article  CAS  PubMed  Google Scholar 

  48. Kim YS, Kim EK, Hwang JW, Seo IB, Jang JH, Son S, Jeong JH, Moon SH, Jeon BT, Park PJ. Characterization of the antioxidant fraction of Trapa japonica pericarp and its hepatic protective effects in vitro and in vivo. Food Funct 2016; 7(3): 1689–1699.

    Article  CAS  PubMed  Google Scholar 

  49. Chen G, Li L. Nutrient consumption and production of isoflavones in bioreactor cultures of Pueraria Iobata (Willd). J Environ Biol 2007; 28(2): 321–326.

    CAS  PubMed  Google Scholar 

  50. Yamazaki T, Hosono T, Matsushita Y, Kawashima K, Someya M, Nakajima Y, Narui K, Hibi Y, Ishizaki M, Kinjo J, Nohara T. Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans. Int J Clin Pharmacol Res 2002; 22(1): 23–28.

    CAS  PubMed  Google Scholar 

  51. Shi P, Chen B, Chen C, Xu J, Shen Z, Miao X, Yao H. Honey reduces blood alcohol concentration but not affects the level of serum MDA and GSH-Px activity in intoxicated male mice models. BMC Complement Altern Med 2015; 15: 225.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Lowenstein LM, Simone R, Boulter P, Nathan P. Effect of fructose on alcohol concentrations in the blood in man. JAMA 1970; 213(11): 1899–1901.

    Article  CAS  PubMed  Google Scholar 

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Author notes

  1. These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Formulation Development, Dong-A Pharmaceutical Co. Ltd., Yongin, Korea

    Jae Young Yu, Hyoung Geun Park & Joon Ho Jun

  2. College of Pharmacy, Yeungnam University, 214-1, Dae-dong, Gyeongsan, 712-749, Korea

    Hanh Thuy Nguyen, Chul Soon Yong & Jong Oh Kim

  3. National Institute of Pharmaceutical Technology, Hanoi University of Pharmacy, Hanoi, Vietnam

    Hanh Thuy Nguyen

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  1. Jae Young Yu
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  2. Hanh Thuy Nguyen
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  4. Hyoung Geun Park
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Corresponding author

Correspondence to Jong Oh Kim.

Additional information

This article has been retracted at the request of authors. It has come to our attention that Seoul National University co-own the data presented in the current study with Dong-A Pharma. Unfortunately, we did not obtain permission to publish the data prior to publication and did not give proper credit to all collaborators on this research project. In addition, authors have been unable to replicate the results presented after conducting further experiments using DA-5513. We are therefore concerned about the reliability of the findings. All authors agreed to this retraction.

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Yu, J.Y., Nguyen, H.T., Yong, C.S. et al. RETRACTED ARTICLE: Effects of DA-5513 on alcohol metabolism and alcoholic fatty liver in rats. Lab Anim Res 34, 49–57 (2018). https://doi.org/10.5625/lar.2018.34.2.49

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  • DOI: https://doi.org/10.5625/lar.2018.34.2.49

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Laboratory Animal Research

ISSN: 2233-7660