Advances in Traditional Medicine

Kyung Hee Oriental Medicine Research Center (경희대학교 융합한의과학연구소)
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Protective effect of methanolic extract of Ganoderma lucidum P. Karst. Reishi from South India against doxorubicin-induced cardiotoxicity in rats

  • Published : 2005.03.30
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Abstract

Doxorubicin is a powerful anticancer antibiotic extensively used in the treatment of several types of cancers. Long-term administration of this drug results in cumulative dose related cardiotoxicity due to enhanced production of free radicals leading to oxidative stress. Our earlier investigations have demonstrated significant antioxidant, anti-inflammatory and antitumour properties of Ganoderma lucidum extracts. We extended our investigations to evaluate the protective effect of Ganoderma lucidum extract against doxorubicin-induced cardiotoxicity. Administration of 3 doses of doxorubicin, 6 mg/kg body weights, i.p. per each dose, alternative days, showed dear signs of cardiotoxicity in rats. The drug enhanced serum creatine kinase (CK) activity and lipid peroxidation in tissue drastically. The drug also induced significant decrease in GSH level and activities of CAT, SOD and GPx. Administration of methanolic extract of G.lucidum (500 and 1,000 mg/kg body weight) significantly increased the level of GSH and activities of CAT, SOD and GPx. Activity of CK was significantly lowered in a dose dependent manner. The treatment also caused significant decrease in lipid peroxidation (MDA). The results thus indicated that methanolic extract of G.lucidum prevented oxidative stress caused by doxorubicin administration and the increase in serum CK activity and lipid peroxidation in the tissue. The experimental findings suggest the therapeutic potential of G.lucidum as adjuvant in cancer chemotherapy.

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References

  1. Childs AC, Phaneuf SL, Dirks AJ, Philips T, Leeuwenburgh C. (2002) Doxorubicin treatment in vivo causes cytochrome c release and cardiomyocytes apoptosis, as well as increased mitochondrial efficiency,superoxide dismutase activity, and Bcl-2: Bax ratio. Cancer Res. 62,4592- 4598.
  2. Doroshow JH. (1983) Effect of anthracycline antibiotics on oxygen radical formation in rat heart. Cancer Res. 43, 460-472.
  3. Dubois M, Gilles GA, Hamiliton JK (1956) Colorimetric estimation of carbohydrates by phenol-sulphuric acid method. Ann. Chem. 28, 350-356. https://doi.org/10.1021/ac60111a017
  4. Hafemann DC, Sunde RA, Houestra We. (1974) Effect of dietary selenium on erythrocyte and liver glutathione peroxidase in the rat. J. Nutr. 104, 580-583. https://doi.org/10.1093/jn/104.5.580
  5. Harbome JB. (1973). Phytochemical Methods, pp. 33-80,Chapman & Hall, London.
  6. Hobbs C. (1995) Medicinal Mushrooms: An exploration of tradition healing and culture, 2nd ed, pp. 251, Botanica Press, Santa Cruz, C A.
  7. Jong SC Birmingham JM. (1992) Edible mushrooms in Biotechnology. Pro. Asian Mycol. Symp. Seoul 18-35.
  8. Jong SC, Birmingham JM. (1992) Medicinal benefits of the mushroom Ganoderma. Adv. Appl. Microbiol. 37, 101-134. https://doi.org/10.1016/S0065-2164(08)70253-3
  9. Jones S, Janardhanan KK. (2000) Antioxidant and antitumor activity of Ganoderma lucidum (Curt.: Fr.) P. Karst.-reishi (Aphyllophoro mycetideae) from South India. Int. J. Med. Mushr. 2, 195-200.
  10. Kang YJ, Chen Y, Epstein PN. (1996) Suppression of doxorubicininduced cardiotoxicity by overexpression of catalase in the heart of transgenic mice. J. Biol. Chem. 271,12610-12616. https://doi.org/10.1074/jbc.271.21.12610
  11. Kang YJ, Chen Y, Yu A, Voss-McCowan M, Epstein PN. (1997) Over expression of metallothionein in the heart of transgenic mice suppresses doxorubicin cardiotoxicity. J. Clin. Investig. 100, 1501-1506. https://doi.org/10.1172/JCI119672
  12. Kottamraju S, Konorev EA, Joseph J, Kalyanaraman B. (2000) Doxorubicin induced apoptosisin endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen: Role of reactive oxygen and nitrogen species. J. BioI. Chem. 275, 33585-33592. https://doi.org/10.1074/jbc.M003890200
  13. Lowry H, Rosenberg NJ, Farr AI, Randa RJ. (1951) Proteinmeasurement with the Folinphenol reagent. J. BioI. Chem. 193, 265-275.
  14. Mc Cord JM, Fridovich1. (1969) Superoxide dismutase, an enzymatic function for erythrocuprein. J. Bioi. Chem. 244, 6049-6055.
  15. Minotti G. (1989) Adriamycin-dependent release of iron from microsomal membranes. Arch. Biochem. Biophys. 268,398-403. https://doi.org/10.1016/0003-9861(89)90601-2
  16. Moron MA, Depierre JW, Mannervik B. (1979) Levels of glutathione reductase and glutathione s-transferace activities in rat lung and liver. Biochem. Biophys. Act. 67, 582-586.
  17. Moss DW, Henderson AR. (1999) Teitz textbook of clinical Chemistry, pp. 662-664, W.B.Sounders Company, Singapore.
  18. Mott MG. (1997) Anthracycline cardiotoxicity and its prevention. Ann. N Y Acad. Sci. 824, 221-228. https://doi.org/10.1111/j.1749-6632.1997.tb46225.x
  19. Naidu MUR, Vijay Kumar K, Krishna Mohan I, Sundaram C, Sashi Singh. (2002) Protective effect of Gingko biloba extract against doxorubicin- induced cardiotoxicity in mice. Ind. J. Exp. Bioi. 40, 894-900.
  20. Ohkawa H, Ohishi N, Yagi K. (1979) Assay for lipid peroxidation in animal tissue by thiobarbituric acid reaction. Annal. Biochem. 95,351-358. https://doi.org/10.1016/0003-2697(79)90738-3
  21. Shan K, Lincoff AM, Young JB. (1996) Anthracycline induced cardiotoxicity. Ann. Intern. Med. 125,47-58. https://doi.org/10.7326/0003-4819-125-1-199607010-00008
  22. Sheena N, Ajith TA, Janardhanan KK. (2003a) Antiinflammatory and antinociceptive activities of Ganoderma lucidum occurring in South India. Pharm. Biol. 41, 301-304. https://doi.org/10.1076/phbi.41.4.301.15677
  23. Sheena N, Ajith TA, JanardhananKK (2003b) Prevention of nephrotoxicity induced by the anticancer drug cisplatin, using Ganoderma lucidum occurring in South India. Curro Sci. 85, 478-482.
  24. Van Acker SABE, Voest EE,Beems DB, Madhuizen HT, Jong JD, Bast A, Van der Vijgh WJF. (1993) Cardioprotective properties of O - (${\beta}$- Hydroxyethyl)rutosides in doxorubicin- pretreated BALB/c mice. Cancer Res. 53, 4603-4607.
  25. Yen HC, Oberley TD, Vichitbandha S, Ho YS, St Clair DK. (1996) The protective role of manganese superoxide dismutase against adriamycin-induced acute cardiac toxicity in transgenic mice. J. Clin. Investig. 98, 1253-1260. https://doi.org/10.1172/JCI118909
  26. Yemm EW, Wills AJ. (1954) The estimation of carbohydrate in plant extract by anthrone. Biochem. J. 57, 508-514. https://doi.org/10.1042/bj0570508