DOI QR코드

DOI QR Code

Effect of High Protein Diet and Resveratrol Supplementation on the Nutritional Status and Immunoreactivity in the Irradiation-induced Inflammatory Rats

방사선 조사된 흰쥐에서 고단백식이와 레스베라트롤 첨가가 영양상태 및 면역기능 증진에 미치는 효과

  • Kim, Kyoung-Ok (Division of Biological Science, College of Science, Sookmyung Women's University) ;
  • Chun, Mi-Son (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Kang, Seung-Hee (Department of Radiation Oncology, Ajou University School of Medicine) ;
  • Kim, Hyun-Sook (Division of Biological Science, College of Science, Sookmyung Women's University)
  • 김경옥 (숙명여자대학교 생명과학부 식품영양과학) ;
  • 전미선 (아주대학교 의과대학 방사선종양학과) ;
  • 강승희 (아주대학교 의과대학 방사선종양학과) ;
  • 김현숙 (숙명여자대학교 생명과학부 식품영양과학)
  • Published : 2009.10.31

Abstract

Most cancer patients are treated with surgery, chemotherapy or radiation as anticancer therapies. Especially in the case of radiation, these treatments produce adverse effects such as vomiting, weight loss, anorexia, normal cell damage and malabsorption. The major goal of this study was to determine the effect of irradiation on the nutritional and immune status in irradiated rats. A secondary goal was to determine the effectiveness of high protein diet (HP) and resveratrol (Res) in minimizing the adverse effects of radiation. Rats were divided into four groups: normal diet (NP), HP, NP + Res and HP + Res groups. Each group was further divided into subgroups that received radiation (RT group) and one that did not (non-RT group). Each diet was supplied from $12^{th}$ day prior to irradiation treatment with irradiation dose of 17.5 Gy. The diets were continued until 10th day after radiation treatment and animals were sacrificed. The radiation treatment showed decreased body weight, serum protein and HDL levels and increased TG and LDL levels in nutritional status. HP, NP + Res and HP + Res groups reduced the level of serum LDL and TG in irradiated rats. NP + Res and HP + Res groups increased reduced albumin level of serum in RT group. In case of immune status, the radiation treat-ment showed decreased WBC, lymphocytes and increased neutrophil and eosinophil levels. The levels of serum IL-2 and IL-6 were significantly increased by radiation, however the cytokine levels decreased in all dietary treatment groups. These results showed that high protein diet and resveratrol supplementation seem to minimize the adverse effects of radiation on lipid nutritional status and inflammation response in the rat model.

방사선 치료는 대부분의 암환자 치료에 적용되고 있다. 그러나 방사선 조사로 인한 부작용으로 환자들은 고통을 받고 있으며, 이러한 방사선치료의 부작용을 줄이고 환자의 영양상태 및 면역기능을 강화시킴으로써 암을 이겨낼 수 있는 능력을 강화시키는 것은 매우 중요한 일이다. 따라서 본 연구에서는 방사선 조사로 염증이 유도된 흰쥐를 사용하여 고단백식이와 레스베라트롤을 식이에 첨가하였을 경우 영양상태와 면역지표에 변화가 있는지를 조사하여 다음과 같은 결론을 얻었다. 1) 방사선 조사로 인한 체중 감소 현상이 모든 군에서 뚜렷하게 나타났다. 정상식이 섭취량에 있어서는 방사선조사 전에는 모든 군에서 유사하게 나타났으나 방사선 치료후 유의하게 식이섭취가 감소하였다. 증가된 IL-6는 leptin의 분비와 단백질 분해를 야기시키고 이로 인하여 식욕감 퇴로 이어져 체중감소가 생긴다. 2) 본 연구에서는 방사선 조사로 인한 영양상태 변화를 살펴 본 결과 혈중 총 단백질과 알부민 농도가 모든 군에서 현저하게 감소하였으며, 레스베라트롤을 식이에 첨가하였을 경우 식이단백질 수준에 상관없이 혈중 알부민 농도를 증가시켰다. 3) 방사선 조사로 인하여 혈중 중성지방 농도가 증가하였으며, LDL-cholesterol 농도의 증가와 함께 HDL-cholesterol 농도가 감소됨으로써 지질 영양상태는 매우 불량한 상태를 초래하였다. 이 경우 단백질 섭취 수준을 높이거나 식이에 레스베라트롤을 첨가한 모든 군에서 혈중 중성지방 농도를 유의하게 감소시킬 수 있었으며, 특히 레스베라트롤을 첨가함으로써 혈중 LDL-cholesterol 수준도 유의하게 낮출 수 있는 것으로 나타났다. 3) 방사선 조사에 따른 혈액세포 수의 변화에 있어서는 유의한 백혈구의 증가와 혈소판의 감소를 들 수 있는데 고단백과 레스베라트롤을 동시에 처리한 군에서 백혈구수를 정상대조군 수준으로 낮출 수 있었으며, 감소된 혈소판 농도는 식이단백질 수준을 높임으로써 정상대조군 수준으로 회복시킬 수 있었다. 4) 또한 본 실험에서는 방사선조사에 의한 백혈구 백분율 변화에 있어서도 림프구의 백분율이 현저하게 감소한 반면 중성구와 호산구의 비율은 유의하게 증가하였다. 이 경우 레스베라트롤 첨가와 무관하게 단백질 섭취 수준을 높임으로써 방사선 조사에 의한 호산구 비율의 증가를 유의하게 낮출 수 있었다. 5) 방사선조사에 의하여 혈중 사이토카인 농도에도 변화가 있었다. 가장 현저한 변화로는 방사선 조사에 의하여 혈중 IL-2와 IL-6의 농도가 유의하게 증가하였으며 두 경우 모두에서 단백질 수준을 높이거나 레스베라트롤을 첨가함으로써 사이토카인의 농도를 정상대조군 수준으로 회복 시켰다. 또한 방사선 조사에 의하여 혈중 IL-12 농도가 현저히 감소하였는데 레스베라트롤을 첨가함으로써 식이단백질 수준에 상관없이 정상대조군 수준으로 증가시켰다. 본 연구의 결과를 통해 항암치료를 위하여 널리 사용되고 있는 방사선 조사는 환자의 영양상태와 면역능에 있어 다양한 변화를 초래함으로써 부작용을 야기시키는 것으로 확인되었다. 이 경우 식이의 단백질 수준을 높이거나 식이에 적정 수준의 레스베라트롤을 첨가함으로써 저하된 환자의 기능을 증진시켜 영양불균형을 개선함과 동시에 면역기능을 높여 염증반응의 부작용을 완화시킬 수 있는 것으로 나타났다.

Keywords

References

  1. Carmia Borek. Antioxidants and radiation therapy. J Nutr 2004; 134(11): 3207S-3209S https://doi.org/10.1093/jn/134.11.3207S
  2. Greenspan D, Xerostomia. Diagnosis and management. Oncology (Williston Park)1996; 10: 7-11
  3. Whitmyer CC, Waskowski JC, Iffland HA. Radiotherapy and oral sequelae: preventive and management protocols. J Dent Hyg 1997; 71(1): 23-29
  4. Jang HJ, Yu HS, Jeon MS, Jang GH, Lee JP. Comparison of Concurrent Chemoradiotherapy Regimen Toxicities in the Treatment of Loco-Regionally Advanced Cervical Cancer. Korean Society of Obstetrics and Gynecology 2004; 47(5): 908-916
  5. Hamberger AD, Unal A, Gershenson DM, Fletcher GH. Analysis of the severe complications of irradiation of carconoma of the cervix: whole pelvis irradiation and intracavitary radium. Int J Radiat Oncol Biol Phys 1983; 9: 367-371 https://doi.org/10.1016/0360-3016(83)90298-5
  6. Weijl NI, Cleton FJ, Osanto S, Free radicals and antioxidants in chemotherapy-induced tosicity. Cancer Treat Rev 1997; 23: 209-240 https://doi.org/10.1016/S0305-7372(97)90012-8
  7. Sangeetha P, Das UN, Koratkar R, Suryaprabha P. Increase in free radical generation and lipid peroxidation following chemotherapy in patients with cancer. Free Radic Biol Med 1990; 8: 15-19 https://doi.org/10.1016/0891-5849(90)90139-A
  8. Durken M, Agbenu J, Finckh B, Hübner C, Pichlmeier U, Eeller W, Winkler K, Zander A, Kohlschütter A. Deteriorating free radicaltrapping capacity and antioxidant status in plasma during bone marrow transplantation. Bone Marrow Transplant 1995; 15: 757-762
  9. Lauterburg BH, Nguyen T, Hartmann B, Junker E, Kupfer A, Cerny T. Depletion of total cysteine, glutathione, and homocysteine in plasma by ifosfamide/mesna therapy. Cancer Chemother Pharmacol 1994; 35: 132-136 https://doi.org/10.1007/BF00686635
  10. Alfonso Vidal, Cristina de la Cuerda, Jose Luis Escat, Irene Breton, Miguel Camblor, Pilar Garcia-Peris. Chronic radiation enteritis after ovarian cancerFrom home parenteral nutrition to oral diet. Clin Nutr 2006; 25: 701-704 https://doi.org/10.1016/j.clnu.2006.04.004
  11. Galland BB, Spencer J. Natural history and surgical management of radiation enteritis. Br J Surg 1987; 74: 742-747 https://doi.org/10.1002/bjs.1800740833
  12. Leiro J, Arranz JA, Fraiz N, Sanmartin ML, Quezada E, Orallo F. Effect of cis-resveratrol on genes involved in nuclear factor kappa B signaling. Int Immunopharmacol 2005; 5(2): 393-406 https://doi.org/10.1016/j.intimp.2004.10.006
  13. Delmas D, Lancon A, Colin D, Jannin B, Latruffe N. Resveratrol as a chemopreventive agent: a promising molecule for fighting cancer. Current Drug Targets 2006 7(4): 423-442 https://doi.org/10.2174/138945006776359331
  14. Faber AC, Chiles TC. Resveratrol induces apoptosis in transformed follicular lymphoma OCI-LY8 cells: evidence for a novel mechanism involving inhibition of BCL6 signaling. Intern J Oncology 2006 29(6): 1561-1566
  15. Riles WL, Erickson J, Nayyar S, Atten MJ, Attar BM, Holian O. Resveratrol engages selective apoptotic signals in gastric adeno-carcinoma cells. World J Gastroenterology 2006; 12(35): 5628-5634 https://doi.org/10.3748/wjg.v12.i35.5628
  16. Sareen D, van Ginkel PR, Takach JC, Mohiuddin A, Darjatmoko SR, Albert DM, Polans AS. Mitochondria as the primary target of resveratrol-induced apoptosis in human retinoblastoma cells. Investigative Ophthamology & Visual Science 2006 47(9): 3708-3716 https://doi.org/10.1167/iovs.06-0119
  17. Faith SA, Sweet TJ, Bailey E, Booth T, Docherty JJ. Resveratrol suppresses nuclear factor-kappaB in herpes simplex virus infected cells. Antiviral Research 2006; 72(3): 242-251 https://doi.org/10.1016/j.antiviral.2006.06.011
  18. Palamara AT, Nencioini L, Aquilano K, et al. Inhibition of influenza A virus replication by resveratrol. J Infectious Diseases 2005; 191(10): 1719-1729 https://doi.org/10.1086/429694
  19. Chun MS, Kang SH, Jin YM, Oh YT, Kil HJ, Ahn BO, Oh TY. Radiation-Induced Proctitis in Rand and Role of Nitric Oxide. J Korean Soc Ther Radiol Oncol 2001; 19(3): 265-274
  20. Dunlop R. Clinical epidemiology of cancer cachexia. In: Bruera E, Higginson I, eds. Cachexia-anorexia in cancer patients. Oxford: Oxford University Press; 1996. p.76-82
  21. MacDonald N, Easson NM, Mazurak VC, Dunn GP, Baracos VE. Understanding and managing cancer cachexia. J Am Coll Surg 2003; 197: 143-161 https://doi.org/10.1016/S1072-7515(03)00382-X
  22. Joanne L Hutton, Lisa Martin, Catherine J Field, Wendy V Wismer, Eduardo D Bruera, Sharon M Watanabe, Vickie E Baracos. Dietry patterns in patients with advanced cancer: implications for anorexia- cachexia therapy. Am J Clin Nutr 2006; 84: 1163-1170 https://doi.org/10.1093/ajcn/84.5.1163
  23. Igura K, Ohta T, Kuroda Y, Kaji K. Resveratrol and quercetin inhibit angiogenesis in vitro. Cancer Lett 2001; 171: 11-16 https://doi.org/10.1016/S0304-3835(01)00443-8
  24. Weiss JF, Landauer MR. Protection against ionizing radiation by antioxidant nutrients and phytochemicals. Toxicology 2003; 189: 1-20 https://doi.org/10.1016/S0300-483X(03)00149-5
  25. Borek C. Antioxidant health effects of aged garlic extract. J Nutr 2001; 131: 1010S-1015S https://doi.org/10.1093/jn/131.3.1010S
  26. Gridley DS, Makinde AY, Luo X, Rizvi A, Crapo JD, Dewhirst MW, Moeller BJ, Pearlstein RD, Slater JM. Radiation and a metalloporphyrin radioprotectant in a mouse prostate tumor model. Anticancer Res 2007; 27(5A): 3101-3109
  27. Sagar SM, Yance D, Wong RK. Natural health products that inhibit angiogenesis: a potential source for investigational new agents to treat cancer-part 2. Current Oncology 2006; 13(3): 99-107
  28. Cole AT, Slater K, Sokal M, Hawkey CJ. In vivo rectal inflammatory mediator changes with radiotherapy to the pelvis. Gut 1993; 34(9): 1210-1214 https://doi.org/10.1136/gut.34.9.1210
  29. Kim TI, Park HJ, Moon HY, Song SY, Kim GE, Cho NH, Park IS. Clinical Investigations Chronic Radiation Proctitis. Korean J Gastroenterol 1996; 28: 28-35
  30. Harding RK, Leach KE, Prud'home-Lalonde L, Ferrarotto CL. Release of inflammatory mediators from irradiated gastrointestinal tissue. Gastroenterology 1990; 102: A258
  31. Lauritsen K, Laursen LS, Bukhave K, Rask-Madsen J. Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E2 and leukotriene B4 levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis. Gastroenterology 1986; 91: 837-844 https://doi.org/10.1016/0016-5085(86)90684-0
  32. Chen Y, Williams J, Ding I, Hernady E, Liu W, Smudzin T, Finkelstein JN, Rubin P, Okunieff P. Radiation pneumonitis and early circulatory cytokines markers. Semin Radiat Oncol 2002; 12: 26-33 https://doi.org/10.1053/srao.2002.31360
  33. Chen Y, Rubin P, Williams J, Hernady E, Smudzin T, Okunieff P. Circulating IL-6 as a predictor of radiation pneumonitis. Int J Radiat Oncol Biol Phys 2001; 49(3): 641-648 https://doi.org/10.1016/S0360-3016(00)01445-0
  34. Indaram AV, Visvalingam V, Locke M, Bank S. Mucosal cytokine production in radiation-induced proctosigmoiditis compared with inflammatory bowel disease. Am J Gastroenterol 2000; 95(5): 1221-1225 https://doi.org/10.1111/j.1572-0241.2000.02013.x
  35. Athar M, Back JH, Kopelovich L, Bickers DR, Kim AL. Multiple molecular targets of resveratrol: Anti-carcinogenic mechanisms. Arch Biochem Biophys 2009; 486(2): 95-102 https://doi.org/10.1016/j.abb.2009.01.018
  36. Goswami SK, Das DK. Resveratrol and chemoprevention. Cancer Lett 2009; 284(1): 1-6 https://doi.org/10.1016/j.canlet.2009.01.041
  37. Brisdelli F, D'Andrea G, Bozzi A. Resveratrol: a natural polyphenol with multiple chemopreventive properties. Curr Drug Metab 2009; 10(6): 530-546 https://doi.org/10.2174/138920009789375423
  38. Li T, Fan GX, Wang W, Li T, Yuan YK. Resveratrol induces apoptosis, influences IL-6 and exerts immunomodulatory effect on mouse lymphocytic leukemia both in vitro and in vivo. Int Immunopharmacol 2007; 7(9): 1221-1231 https://doi.org/10.1016/j.intimp.2007.05.008
  39. Xiaohua Gao, Yong X. Xu, Nalini Janakiraman, Robert A. Chapman, Subhash C. Gautam. Immunomodulatory activity of resveratrol: suppression of lymphocyte proliferation, development of cell-mediated cytotoxicity, and cytokine production. Biochemical Pharmacology 2001; 62: 1299-1308 https://doi.org/10.1016/S0006-2952(01)00775-4

Cited by

  1. Hesperidin Partially Restores Impaired Immune and Nutritional Function in Irradiated Mice vol.14, pp.5, 2011, https://doi.org/10.1089/jmf.2010.1269
  2. Effect of quercetin on impaired immune function in mice exposed to irradiation vol.6, pp.4, 2012, https://doi.org/10.4162/nrp.2012.6.4.301
  3. Korean Traditional Natural Herbs and Plants as Immune Enhancing, Antidiabetic, Chemopreventive, and Antioxidative Agents: A Narrative Review and Perspective vol.17, pp.1, 2014, https://doi.org/10.1089/jmf.2013.3059