The Journal of Korean Medicine (대한한의학회지)

The Society of Korean Medicine (대한한의학회)
권호 표지

Anti-Myelosuppression Effects of Korean Red Ginseng in SD Rat Injected with 5-fluorouracil

  • Park, Hye-Jung (Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University) ;
  • Han, Jong-Min (Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University) ;
  • Kim, Hyeong-Geug (Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University) ;
  • Choi, Min-Kyung (Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University) ;
  • Lee, Jin-Seok (Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University) ;
  • Son, Chang-Gue (Liver and Immunology Research Center, Daejeon Oriental Hospital of Oriental Medical College of Daejeon University)
  • Received : 2012.05.04
  • Accepted : 2012.06.11
  • Published : 2012.06.30
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives: This study aimed to investigate the preventive effect of red ginseng (RG) on 5-fluorouracil (5-FU)-induced side effects focusing on myelosuppression. Methods: Rats (n = 50) were divided into five groups, nave, control (ip, 5-FU injection of 150 mg/kg), and RG pre-treatment (po, 25, 50 and 100 mg/kg for 5 days before 5-FU injection). On the $7^{th}$ day after 5-FU injection, we evaluated the effects using peripheral hematological parameters, colony-forming assay, cytokine levels and histopathological finding. Results: The peripheral white blood cell and the differential count were dramatically suppressed by 5-FU, while RG (50 and 100 mg/kg) treatment significantly improved total white blood cell, neutrophil, lymphocyte and platelet counts. Also, RG (100 mg/kg) pre-treatment significantly increased the number of CFU-GM colony compared with the control group. RG pre-treatment also ameliorated the histopathological damage in bone marrow, spleen, stomach and small intestine tissue. Conclusions: These results demonstrate that Korean RG has preventive effects against 5-FU-induced myelotoxicity and gastrointestinal damage.

Keywords

References

  1. Griggs JJ. Reducing the toxicity of anticancer therapy: new strategies. Leuk Res 1998; 22 Suppl 1:S27-S33. https://doi.org/10.1016/S0145-2126(98)00036-8
  2. Kopecna L. Late effects of anticancer therapy on kidney function in children with acute lymphoblastic leukemia. Bratisl Lek Listy 2001; 102(8):357-360.
  3. Gustafsson LL, Eriksson LS, Dahl ML, Eleborg L, Ericzon BG, Nyberg A. Cyclophosphamideinduced acute liver failure requiring transplantation in a patient with genetically deficient debrisoquine metabolism: a causal relationship? J Intern Med 1996; 240(5):311-314. https://doi.org/10.1046/j.1365-2796.1996.42867000.x
  4. Fernandez-Ortega P, Caloto MT, Chirveches E, Marquilles R, Francisco JS, Quesada A, et al. Chemotherapy-induced nausea and vomiting in clinical practice: impact on patients' quality of life. Support Care Cancer 2012.
  5. Grem JL. 5-Fluorouracil: forty-plus and still ticking. A review of its preclinical and clinical development. Invest New Drugs 2000; 18(4):299-313. https://doi.org/10.1023/A:1006416410198
  6. Toxicity of fluorouracil in patients with advanced colorectal cancer: effect of administration schedule and prognostic factors. Meta-Analysis Group In Cancer. J Clin Oncol 1998; 16(11):3537-3541. https://doi.org/10.1200/JCO.1998.16.11.3537
  7. Tomiak A, Vincent M, Kocha W, Taylor M, Winquist E, Keith B, et al. Standard dose (Mayo regimen) 5-fluorouracil and low dose folinic acid: prohibitive toxicity? Am J Clin Oncol 2000; 23(1):94-98. https://doi.org/10.1097/00000421-200002000-00025
  8. Jodrell DI, Stewart M, Aird R, Knowles G, Bowman A, Wall L, et al. 5-fluorouracil steady state pharmacokinetics and outcome in patients receiving protracted venous infusion for advanced colorectal cancer. Br J Cancer 2001; 84(5):600-603 https://doi.org/10.1054/bjoc.2000.1664
  9. Park D, Bae DK, Jeon JH, Lee J, Oh N, Yang G, et al. Immunopotentiation and antitumor effects of a ginsenoside Rg-fortified red ginseng preparation in mice bearing H460 lung cancer cells. Environ Toxicol Pharmacol 2011; 31(3):397-405 https://doi.org/10.1016/j.etap.2011.01.008
  10. Oyagi A, Ogawa K, Kakino M, Hara H. Protective effects of a gastrointestinal agent containing Korean red ginseng on gastric ulcer models in mice. BMC Complement Altern Med 2010; 10:45. https://doi.org/10.1186/1472-6882-10-45
  11. Lee HJ, Kim JS, Song MS, Seo HS, Moon C, Kim JC, et al. Photoprotective effect of red ginseng against ultraviolet radiation-induced chronic skin damage in the hairless mouse. Phytother Res 2009; 23(3):399-403. https://doi.org/10.1002/ptr.2640
  12. Shin HJ, Kim YS, Kwak YS, Song YB, Park JD. Enhancement of antitumor effects of paclitaxel (taxol) in combination with red ginseng acidic polysaccharide(RGAP). Planta Med 2004; 70 (11):1033-1038. https://doi.org/10.1055/s-2004-832643
  13. Kim JH, Yoon IS, Lee BH, Choi SH, Lee JH, Jeong SM, et al. Effects of Korean red ginseng extract on cisplatin-induced nausea and vomiting. Arch Pharm Res 2005; 28(6):680-684. https://doi.org/10.1007/BF02969358
  14. Joo SS, Won TJ, Kim MS, Lee DI. Hematopoietic effect of ginsenoside Rg3 in ICR mouse primary cultures and its application to a biological response modifier. Fitoterapia 2004; 75(3-4): 337-341. https://doi.org/10.1016/j.fitote.2004.02.008
  15. Sassi G, Striano B, Merlo UA. A reporting system for the assessment of chemotherapy toxicity. J Oncol Pharm Pract 2005; 11(2):63-67. https://doi.org/10.1191/1078155205jp154oa
  16. Earl HM, Hiller L, Dunn JA, Bathers S, Harvey P, Stanley A, et al. NEAT: National Epirubicin Adjuvant Trial--toxicity, delivered dose intensity and quality of life. Br J Cancer 2008; 99(8):1226-1231. https://doi.org/10.1038/sj.bjc.6604674
  17. Meyerhardt JA, Mayer RJ. Systemic therapy for colorectal cancer. N Engl J Med 2005; 352(5): 476-487. https://doi.org/10.1056/NEJMra040958
  18. Saegusa Y, Ichikawa T, Iwai T, Goso Y, Ikezawa T, Nakano M, et al. Effects of acid antisecretory drugs on mucus barrier of the rat against 5- fluorouracil-induced gastrointestinal mucositis. Scand J Gastroenterol 2008; 43(5):531-537. https://doi.org/10.1080/00365520701811693
  19. Nag SA, Qin JJ, Wang W, Wang MH, Wang H, Zhang R. Ginsenosides as Anticancer Agents: In vitro and in vivo Activities, Structure-Activity Relationships, and Molecular Mechanisms of Action. Front Pharmacol 2012; 3:25.
  20. Zhang QH, Wu CF, Duan L, YangJY. Protective effects of total saponins from stem and leaf of Panax ginseng against cyclophosphamide-induced genotoxicity and apoptosis in mouse bone marrow cells and peripheral lymphocyte cells. Food Chem Toxicol 2008; 46(1):293-302. https://doi.org/10.1016/j.fct.2007.08.025
  21. Lee JI, Ha YW, Choi TW, Kim HJ, Kim SM, Jang HJ, et al. Cellular uptake of ginsenosides in Korean white ginseng and red ginseng and their apoptotic activities in human breast cancer cells. Planta Med 2011; 77(2):133-140. https://doi.org/10.1055/s-0030-1250160
  22. Kim JH, Kang SA, Han SM, Shim I. Comparison of the antiobesity effects of the protopanaxadioland protopanaxatriol-type saponins of red ginseng. Phytother Res 2009; 23(1):78-85. https://doi.org/10.1002/ptr.2561
  23. Yang Y, Xu S, Xu Q, Liu X, Gao Y, Steinmetz A, et al. Protective effect of dammarane sapogenins against chemotherapy-induced myelosuppression in mice. Exp Biol Med (Maywood) 2011; 236 (6):729-735. https://doi.org/10.1258/ebm.2011.010369
  24. Kojima S, Takaba K, Kimoto N, Takeda T, Kakuni M, Mizutani M, et al. Protective effects of glutathione on 5-fluorouracil-induced myelosuppression in mice. Arch Toxicol 2003; 77(5):285-290. https://doi.org/10.1007/s00204-003-0448-9
  25. Takano F, Tanaka T, Aoi J, Yahagi N, Fushiya S. Protective effect of (+)-catechin against 5- fluorouracil-induced myelosuppression in mice. Toxicology 2004; 201(1-3):133-142. https://doi.org/10.1016/j.tox.2004.04.009
  26. Eaves AC, Bruce WR. [Altered sensitivity of hematopoietic stem cells to 5-fluorouracil (NSC- 19893) following endotoxin(NSC-189681), cyclophosphamide( NSC-26271), or irradiation]. Cancer Chemother Rep 1974; 58(6):813-820.
  27. Shin JW, Lee MM, Son JY, Lee NH, Cho CK, Chung WK, et al. Myelophil, a mixture of Astragali Radix and Salviae Radix extract, moderates toxic side effects of fluorouracil in mice. World J Gastroenterol 2008; 14(15):2323- 2328. https://doi.org/10.3748/wjg.14.2323
  28. Raghavendran HR, Rekha S, Shin JW, Kim HG, Wang JH, Park HJ, et al. Effects of Korean ginseng root extract on cisplatin-induced emesis in a rat-pica model. Food Chem Toxicol 2011; 49(1):215-221. https://doi.org/10.1016/j.fct.2010.10.019
  29. Raghavendran HR, Sathyanath R, Shin J, Kim HK, Han JM, Cho J, et al. Panax ginseng Modulates Cytokines in Bone Marrow Toxicity and Myelopoiesis: GinsenosideRg1 Partially Supports Myelopoiesis. PLoS One 2012; 7(4):e33733. https://doi.org/10.1371/journal.pone.0033733
  30. Kaushansky K. Lineage-specific hematopoietic growth factors. N Engl J Med 2006; 354(19): 2034-2045. https://doi.org/10.1056/NEJMra052706
  31. Koike K, Ogawa M, Ihle JN, Miyake T, Shimizu T, Miyajima A, et al. Recombinant murine granulocyte-macrophage(GM) colony-stimulating factor supports formation of GM and multipotential blast cell colonies in culture: comparison with the effects of interleukin-3. J Cell Physiol 1987; 131(3):458-464. https://doi.org/10.1002/jcp.1041310319
  32. Leary AG, Yang YC, Clark SC, Gasson JC, Golde DW, Ogawa M. Recombinant gibbon interleukin 3 supports formation of human multilineage colonies and blast cell colonies in culture: comparison with recombinant human granulocyte-macrophage colony-stimulating factor. Blood 1987; 70(5):1343-1348.
  33. Takaba J, Mishima Y, Hatake K, Kasahara T. Role of bone marrow-derived monocytes/macrophages in the repair of mucosal damage caused by irradiation and/or anticancer drugs in colitis model. Mediators Inflamm 2010; 2010:634145.
  34. Sonis ST. Regimen-related gastrointestinal toxicities in cancer patients. Curr Opin Support Palliat Care 2010; 4(1):26-30. https://doi.org/10.1097/SPC.0b013e328335fb76
  35. Sonis ST, Elting LS, Keefe D, Peterson DE, Schubert M, Hauer-Jensen M, et al. Perspectives on cancer therapy-induced mucosal injury: pathogenesis, measurement, epidemiology, and consequences for patients. Cancer 2004; 100(9 Suppl):1995-2025.