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Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury

  • Jang, Sun-Hee (Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University) ;
  • Cho, Sung-Woo (Department of Oriental Rehabilitation Medicine, College of Korean Medicine, Dong-Eui University) ;
  • Yoon, Hyun-Min (Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University) ;
  • Jang, Kyung-Jeon (Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University) ;
  • Song, Chun-Ho (Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University) ;
  • Kim, Cheol-Hong (Department of Acupuncture & Moxibution, College of Korean Medicine and Research Institute of Korean Medicine, Dong-Eui University)
  • Received : 2014.08.25
  • Accepted : 2014.09.11
  • Published : 2014.09.30

Abstract

Objectives: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. Methods: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. Results: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. Conclusion: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress.

Keywords

References

  1. Singal AK, Chaha KS, Rasheed K, Anand BS. Liver transplantation in alcoholic liver disease current status and controversies. World J Gastroenterol. 2013;19(36):5953-63. https://doi.org/10.3748/wjg.v19.i36.5953
  2. Gao B, Bataller R. Alcoholic liver disease: pathogenesis and new therapeutic targets. Gastroenterology. 2011;141(5):1572-85. https://doi.org/10.1053/j.gastro.2011.09.002
  3. Osterreicher CH, Halangk J, Berg T, Patsenker E, Homann N, Hellerbrand C, et al. Evaluation of the transforming growth factor beta1 codon 25 (Arg $\rightarrow$ Pro) polymorphism in alcoholic liver disease. Cytokine. 2008;42(1):18-23. https://doi.org/10.1016/j.cyto.2008.02.003
  4. Meier P, Seitz HK. Age, alcohol metabolism and liver disease. Curr Opin Clin Nutr Metab Care. 2008;11(1):21-6. https://doi.org/10.1097/MCO.0b013e3282f30564
  5. Tuma DJ, Casey CA. Dangerous byproducts of alcohol breakdown-focus on adducts. Alcohol Res Health. 2003;27(4):285-90.
  6. Albano E, French SW, Ingelman-Sundberg M. Hydroxyethyl radicals in ethanol hepatotoxicity. Front Biosci. 1999;4:533-40. https://doi.org/10.2741/Albano
  7. Wu D, Cederbaum AI. Alcohol, oxidative stress, and free radical damage. Alcohol Res Health. 2003;27(4):277-84.
  8. Leung TM, Nieto N. CYP2E1 and oxidant stress in alcoholic and non-alcoholic fatty liver disease. J Hepatol. 2013;58(2):395-8. https://doi.org/10.1016/j.jhep.2012.08.018
  9. Cederbaum AI, Lu Y, Wu D. Role of oxidative stress in alcohol-induced liver injury. Arch Toxicol. 2009;83(6):519-48. https://doi.org/10.1007/s00204-009-0432-0
  10. Wu D, Cederbaum AI. Oxidative stress and alcoholic liver disease. Semin Liver Dis. 2009;29(2):141-54. https://doi.org/10.1055/s-0029-1214370
  11. Koch OR, Pani G, Borrello S, Colavitti R, Cravero A, Farre S, et al. Oxidative stress and antioxidant defenses in ethanol-induced cell injury. Mol Aspects Med. 2004;25(1-2):191-8. https://doi.org/10.1016/j.mam.2004.02.019
  12. Singh M, Gupta S, Singhal U, Pandey R, Aggarwal SK. Evaluation of the oxidative stress in chronic alcoholics. J Clin Diagn Res. 2013;7(8):1568-71.
  13. Zeng T, Zhang CL, Song FY, Zhao XL, Yu LH, Zhu ZP, et al. The activation of HO-1/Nrf-2 contributes to the protective effects of diallyl disulfide (DADS) against ethanol-induced oxidative stress. Biochim Biophys Acta. 2013;1830(10):4848-59. https://doi.org/10.1016/j.bbagen.2013.06.028
  14. Bianchi GP, Fiorella PL, Bargossi AM, Grossi G, Marchesini G. Reduced ubiquinone plasma levels in patients with liver cirrhosis and in chronic alcoholics. Liver. 1994;14(3):138-40.
  15. Kim JD, Kang DI. A descriptive statistical approach to the Korean pharmacopuncture therapy. J Acupunct Meridian Stud. 2010;3(3):141-9. https://doi.org/10.1016/S2005-2901(10)60029-5
  16. Yin CS, Park HJ, Chae YB, Ha EY, Park HK, Lee HS, et al. Korean acupuncture: the individualized and practical acupuncture. Neurol Res. 2007;29 Suppl 1:S10-5. https://doi.org/10.1179/016164107X172301
  17. Xu Z, Chen X, Zhong Z, Chen L, Wang Y. Ganoderma lucidum polysaccharides: immunomodulation and potential anti-tumor activities. Am J Chin Med. 2011;39(1):15-27. https://doi.org/10.1142/S0192415X11008610
  18. Weng CJ, Yen GC. The in vitro and in vivo experimental evidences disclose the chemopreventive effects of ganoderma lucidum on cancer invasion and metastasis. Clin Exp Metastasis. 2010;27(5):361-9. https://doi.org/10.1007/s10585-010-9334-z
  19. Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, Bisen PS. Ganoderma lucidum: a potent pharmacological macrofungus. Curr Pharm Biotechnol. 2009;10(8):717-42. https://doi.org/10.2174/138920109789978757
  20. Boh B, Berovic M, Zhang J, Zhi-Bin L. Ganoderma lucidum and its pharmaceutically active compounds. Biotechnol Annu Rev. 2007:13:265-301. https://doi.org/10.1016/S1387-2656(07)13010-6
  21. Chen P, Wang Z, Zeng L, Yang X, Wang S, Dong W, et al. A novel soluble beta-glucan salecan protects against acute alcoholinduced hepatotoxicity in mice. Bioscience, Biotechnology and Biochemistry. 2011;75:1990-93. https://doi.org/10.1271/bbb.110412
  22. Misra HP, Fridovich I. The role of superoxide anion in the autoxidation of epinephrine and a simple assay for superoxide dismutase. J Biol Chem. 1972;247(10):3170-5.
  23. Reuben A. Alcohol and the liver. Curr Opin Gastroenterol. 2006;22(3):263-71.
  24. Bergheim I, McClain CJ, Arteel GE. Treatment of alcoholic liver disease. Dig Dis. 2005;23(3-4):275-84. https://doi.org/10.1159/000090175
  25. Maddrey WC. Alcohol-induced liver disease. Clin Liver Dis. 2000;4(1):115-31. https://doi.org/10.1016/S1089-3261(05)70099-4
  26. Nordmann R. Alcohol and antioxidant systems. Alcohol and Alcoholism. 1994;29(5):513-22.
  27. Kurose I, Higuchi H, Kato S, Miura S, Watanabe N, Kamegaya Y, et al. Oxidative stress on mitochondria and cell membrane of cultured rat hepatocytes and perfused liver exposed to ethanol. Gastroenterology. 1997;112(4):1331-43. https://doi.org/10.1016/S0016-5085(97)70147-1
  28. Rouach H, Fataccioli V, Gentil M, French SW, Morimoto M, Nordmann R. Effect of chronic ethanol feeding on lipid peroxidation and protein oxidation in relation to liver pathology. Hepatology. 1997;25(2):351-5. https://doi.org/10.1002/hep.510250216
  29. Wieland P, Lauterburg BH. Oxidation of mitochondrial proteins and DNA following administration of ethanol. Biochem Biophys Res Commun. 1995;213(3):815-9. https://doi.org/10.1006/bbrc.1995.2202
  30. Masini A, Ceccarelli D, Gallesi D, Giovannini F, Trenti T. Lipid hydroperoxide induced mitochondrial dysfunction following acute ethanol intoxication in rats. the critical role for mitochondrial reduced glutathione. Biochem Pharmacol. 1994;47(2):217-24. https://doi.org/10.1016/0006-2952(94)90009-4
  31. Bury RW, Desmond PV, Mashford ML, Westwood B, Shaw G, Breen KJ. The effect of ethanol administration on the disposition and elimination of chlormethiazole. Eur J Clin Pharmacol. 1983;24(3):383-5. https://doi.org/10.1007/BF00610059
  32. Nagy LE. Molecular aspects of alcohol metabolism: transcription factors involved in early ethanol-induced liver injury. Annu Rev Nutr. 2004;24:55-78. https://doi.org/10.1146/annurev.nutr.24.012003.132258
  33. Zeng T, Xie KQ. Ethanol and liver: recent advances in the mechanisms of ethanol-induced hepatosteatosis. Arch Toxicol. 2009;83(12):1075-81. https://doi.org/10.1007/s00204-009-0457-4
  34. Kim YJ, Kim MC, Lee CH, Kim JU, Yook TH. The effect of needle-embedding therapy and pharmacopuncture therapy on patients with urinary incontinence. J Acupunct Meridian Stud. 2011;4(4):220-4. https://doi.org/10.1016/j.jams.2011.10.012
  35. Boh B. Ganoderma lucidum: a potential for biotechnological production of anti-cancer and immunomodulatory drugs. Recent Pat Anticancer Drug Discov. 2013;8(3):255-87. https://doi.org/10.2174/1574891X113089990036
  36. Wu GS, Guo JJ, Bao JL, Li XW, Chen XP, Lu JJ, et al. Anti-cancer properties of triterpenoids isolated from Ganoderma lucidum - a review. Expert Opin Investig Drugs. 2013;22(8):981-92. https://doi.org/10.1517/13543784.2013.805202
  37. Wu X, Zeng J, Hu J, Liao Q, Zhou R, Zhang P, et al. Hepatoprotective effects of aqueous extract from lingzhi or reishi medicinal mushroom Ganoderma lucidum (higher basidiomycetes) on α-amanitin-induced liver injury in mice. Int J Med Mushrooms. 2013;15(4):383-91. https://doi.org/10.1615/IntJMedMushr.v15.i4.60
  38. Orman ES, Odena G, Bataller R. Alcoholic liver disease: pathogenesis, management, and novel targets for therapy. J Gastroenterol Hepatol. 2013;28 Suppl 1:77-84. https://doi.org/10.1111/jgh.12030
  39. Crawford JM. Histologic findings in alcoholic liver disease. Clin Liver Dis. 2012;16(4):699-716. https://doi.org/10.1016/j.cld.2012.08.004
  40. Helander A. Biological markers in alcoholism. J Neural Transm Suppl. 2003;(66):15-32.
  41. Sharpe PC. Biochemical detection and monitoring of alcohol abuse and abstinence. Ann Clin Biochem. 2001;38(6):652-64. https://doi.org/10.1258/0004563011901064
  42. Panda V, Ashar H, Srinath S. Antioxidant and hepatoprotective effect of garcinia indica fruit rind in ethanol-induced hepatic damage in rodents. Interdiscip Toxicol. 2012;5(4):207-13.
  43. Conigrave KM, Davies P, Haber P, Whitfield JB. Traditional markers of excessive alcohol use. Addiction. 2003;98 Suppl 2:31-43 . https://doi.org/10.1046/j.1359-6357.2003.00581.x
  44. Amacher DE. Serum transaminase elevations as indicators of hepatic injury following the administration of drugs. Regul Toxicol Pharmacol. 1998;27(2):119-30. https://doi.org/10.1006/rtph.1998.1201
  45. Dey A, Cederbaum AI. Alcohol and oxidative liver injury. Hepatology. 2006;43 Suppl 1:S63-74. https://doi.org/10.1002/hep.20957
  46. Singal AK, Jampana SC, Weinman SA. Antioxidants as therapeutic agents for liver disease. Liver Int. 2011;31(10):1432-48. https://doi.org/10.1111/j.1478-3231.2011.02604.x
  47. Dinda PK, Kossev P, Beck IT, Buell MG. Role of xanthine oxidase-derived oxidants and leukocytes in ethanol-induced jejunal mucosal injury. Dig Dis Sci. 1996;41(12):2461-70. https://doi.org/10.1007/BF02100144
  48. Thuluvath PJ, Triger DR. Selenium in chronic liver disease. J Hepatol. 1992;14(2-3):176-82. https://doi.org/10.1016/0168-8278(92)90155-I

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