Low molecular weight β-glucan stimulates doxorubicin-induced suppression of immune functions in mice

Springer Science and Business Media LLC - Tập 21 - Trang 645-651 - 2012
Nak-Yun Sung1, Eui-Baek Byun1, Du-Sup Song1, Young-Choon Yoo2, Jae-Kyung Kim1, Jong-Heum Park1, Beom-Seok Song1, Sang-Hyun Park1, Ju-Woon Lee1, Young-Beob Yu3, Jae-Hun Kim1
1Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup, Jeonbuk, Korea
2Myonggok Institute of Medical Science, College of Medicine, Konyang University, Daejeon, Korea
3Department of Herbal Pharmaceutical Development, Nambu University, Gwangju, Korea

Tóm tắt

The aim of this study was to evaluate the protective effect of low molecular weight β-glucan (LMG) against doxorubicin (DOX)-induced immune suppression of tumor-bearing mice. The tumor size and spleen cell functions such as spleen cell proliferation, cytokine production (interferon-γ and interleukin-2), and the population of CD4+ and CD8+ T cells were estimated. In the tumorbearing mice, the tumor size was significantly (p<0.05) decreased by DOX treatment. However, there was no significant difference between mice treated with high molecular weight β-glucan (HMG) and mice treated with LMG. Spleen cell proliferation and cytokine production were significantly (p<0.05) decreased in only DOX treated group, but increased in all β-glucan treated groups with DOX. Moreover, the populations of CD4+ and CD8+ T cells were also increased in the LMG-treated group. It appears that LMG effectively reduces the DOX-induced immune toxicity through activation of immune cells such as splenocytes.

Tài liệu tham khảo

Kang JK, Lee YJ, No KO, Jung EY, Sung JH, Kim YB, Nam SY. Ginseng intestinal metabolite-I (GIM-I) reduces doxorubicin toxicity in the mouse testis. Reprod. Toxicol. 16: 291–298 (2002) Wasptra FH. Van Goor H, De Jong PE, Navis GJ, De Zeeuw D. Dose of doxorubicin determines severity of renal damage and responsiveness to ACE-inhibition in experimental nephrosis. J. Pharmacol. Toxicol. 41: 69–73 (1999) Richardson DS, Johnson SA. Anthracyclines in haematology: Preclinical studies, toxicity, and delivery systems. Blood Rev. 11: 201–223 (1997) Bernuzzi F, Recalcati S, Alberghini A, Cairo G. Reactive oxygen species-independent apoptosis in doxorubicin-treated H9c2 cardiomyocytes: Role for heme oxygenase-1 down-modulation. Chem.-Biol. Interact. 177: 12–20 (2009) Masse A, Ramirez LH, Bindoula G, Grillon C, Wdzieczak-Bakala J, Raddassi E, Deschamps de Paillette E, Mencia-Huerta JM, Koscielny S, Potier P, Sainteny F, Carde P. The tetrapeptide acetyl-N-Ser-Asp-Lys-Pro (goralatide) protects from doxorubicin-induced toxicity: Improvement in mice survival and protection of bone marrow stem cells and progenitors. Blood 91: 441–449 (1998) Lin H, She YH, Cassileth BR, Sirotnak F, Rundles SC. Maitake β-glucan MD-fraction enhances bone marrow colony formation and reduces doxorubicin toxicity in vitro. Int. Immunopharmacol. 4: 91–99 (2004) Olson LE, Bedja D, Alvey SJ, Cardounel AJ, Gabrielson KL, Reeves RH. Protection from doxorubicin-induced cardiac toxicity in mice with a null allele of carbonyl reductase-1. Cancer Res. 63: 6602–6606 (2003) Yagmurca M, Bas O, Mollaoglu H, Sahin O, Nacar A, Karaman O, Songurb A. Protective effects of erdosteine on doxorubicin-induced hepatotoxicity in rats. Arch. Med. Res. 38: 380–385 (2007) Lee JW, Sung NY, Kim JK, Kim JH, Raghavendran HRB, Yoo YC, Shin MG, Byun MW. Effect of γ irradiation on the spleen cell function and cytotoxicity of doxorubicin. Chem. -Biol. Interact. 173: 205–214 (2008) Brown GD, Gordon S. Fungal β-glucans and mammalian immunity. Immunity 19: 311–315 (2003) Goldman RC. Biological response modification by β-d-glucans. Annu. Rep. Med. Chem. 30: 129–138 (1995) Ross GD, Vetvicka V, Yan J, Xia Y, Vetvickova J. Therapeutic intervention with complement and β-glucans in cancer. Int. Immunopharmacol. 42: 61–74 (1999) Borchers AT, Keen CL, Gershwin ME. Minireview-mushrooms, tumors, and immunity: An update. Exp. Biol. Med. 229: 393–406 (2004) Kim JH, Sung NY, Byun EH, Kwon SK, Song BS, Choi J, Yoon Y, Kim JK, Byun MW, Lee JW. Effects of γ irradiation on immunological activities of β-glucan. Food Sci. Biotechnol. 18: 1305–1309 (2009) Lee JW, Byun EH, Sung NY, Raghavendran HRB, Byun EB, Kim JH, Choi J, Shin MG, Byun MW. Effect of γ irradiation on the efficacy of β-glucan against acetaminophen induced toxicity in mice. Chem. -Biol. Interact. 180: 98–105 (2008) Byun EH, Kim JH, Sung NY, Choi J, Lim ST, Kim KH, Yook HS, Byun MW, Lee JW. Effects of β-irradiation on the physical and structural properties of β-glucan. Radiat. Phys. Chem. 77: 781–786 (2008) Zhanga XY, Lib WG, Wub YJ, Zhenga TZ, Lia W, Qu SY, Liu NF. Proanthocyanidin from grape seeds potentiates anti-tumor activity of doxorubicin via immunomodulatory mechanism. Int. Immunopharmacol. 5: 1247–1257 (2005) Carter SK. Adriamycin-A review. J. Natl. Cancer Inst. 55: 1265–1274 (1975) Gabbay EJ, Grier D, Fingerle RE, Reimer R, Levy R, Pearce SW, Wilson WD. Interaction specificity of the anthracyclines with deoxyribonucleic acid. Biochemistry 15: 2062–2070 (1976) Dimarco A, Zunino F, Silvestrinic R, Gambarucci C, Gambetta RA. Interaction of some daunomycin derivatives with deoxyribonucleic acid and their biological activity. Biochem. Pharmacol. 20: 1323–1328 (1971) Dalloz F, Maingon P, Cottin Y, Briot F, Horiot JC, Rochette L. Effects of combined irradiation and doxorubicin treatment: On cardiac function and antioxidant defenses in the rat. Free Radical Bio. Med. 26: 785–800 (1999) Gibaud S, Andreux JP, Weingarten C, Renard M, Couvreur P. Increased bone marrow toxicity of doxorubicin bound to nanoparticles. Eur. J. Cancer 30: 820–826 (1994) Elsea CR, Elsea DA, Roberts, Druker BJ, Wood LJ. Inhibition of p38 MAPK suppresses inflammatory cytokine induction by etoposide, 5-fluorouracil, and doxorubicin without affecting tumoricidal activity. PLoS ONE 3: e2355 (2008) Vereschagin EI, Van Lambalgen AA, Dushkin MI, Schwartz YS, Polyakov L, Heemskerk A, Huisamn E, Thijs LG, van den Bos GC. Soluble glucan protects against endotoxin shock in the rat: The role of the scavenger receptor. Shock 9: 193–198 (1998) Chen J, Seviour R. Medicinal importance of fungal β-(13), (16)-glucans, Mycol. Res. 111: 635–652 (2007) Tada R, Yoshikawa M, Kuge T, Tanioka A, Ishibashi K, Adachi Y, Tsubaki K, Ohno N. A highly branched 1,3-β-D-glucan extracted from Aureobasidium pullulans induces cytokine production in DBA/2 mouse-derived splenocytes. Int. Immunopharmacol. 9: 1431–1436 (2009) Lehmann J, Kunze R. Water-soluble low-molecular-weight β-glucans for modulating immunological responses in mammalian system. U.S. Patent 6,143,883 (2000) Vetvicka V, Dvorak B, Vetvickova J, Richter J, Krizan J, Sima P, Yvin JC. Orally administered marine (13)-β-d-glucan phycarine stimulates both humoral and cellular immunity. Int. J. Biol. Macromol. 40: 291–298 (2007) Rice PJ, Lockhart BE, Barker LA, Adams EL, Ensley HE, Williams DL. Pharmacokinetics of fungal (1–3)-β-d-glucans following intravenous administration in rats. Int. Immunopharmacol. 4: 1209–1215 (2004) Cheung NK, Modak S, Vickers A, Knuckles B. Orally administered β-glucans enhance anti-tumor effects of monoclonal antibodies. Cancer Immunol. Immun. 51: 557–564 (2002) Neutra MR, Phillips TL, Mayer EL, Fishkind DJ. Transport of membrane-bound macromolecules by M cells in follicle-associated epithelium of rabbit Peyer’s patch. Cell Tissue Res. 86: 345–348 (1987) Owen RL. Uptake and transport of intestinal macromolecules and microorganisms by M cells in Peyer’s patches-a personal and historical perspective. Semin. Immunol. 11: 157–163 (1999) Liang E, Kabcenell AK, Coleman JR, Robson J, Ruffles R, Yazdanian M. Permeability measurement of macromolecules and assessment of mucosal antigen sampling using in vitro converted M cells. J. Pharmacol. Toxicol. 46: 93–101 (2002) Sung NY, Byun EH, Kwon SK, Song BS, Choi J, Kim JH, Byun MW, Yoo YC, Kim MR, Lee JW. Immune-enhancing activities of low molecular weight β-glucan depolymerized by γ irradiation. Radiat. Phys. Chem. 78: 433–436 (2009) Suzanne OR. Immune surveillance: A balance between protumor and antitumor immunity. Curr. Opin. Genet. Dev. 18: 1–8 (2007) Earvin L, Alisa KK, James RC, John R, Royal R, Mehran Y. Permeability measurement of macromolecules and assessment of mucosal antigen sampling using in vitro converted M cells. J. Phamacol. Toxicol. 46: 93–101 (2002)