Improvement of Hematopoietic and Immunologic Findings in Sublethal Gamma Irradiated Rats Treated with Bone Marrow Transplantation and Wheat Germ Oil


The objective of this study was to evaluate the efficacy of the wheat germ oil (WGO) and bone marrow transplantation (BMT) in boosting the immuno response and protecting from oxidative stress in irradiated rats. BM was given by intravenous injection to male rats, one hour post gamma irradiation at the dose level of 5 Gy. Rats were orally administrated with 54 mg/Kg body wt of wheat germ oil daily for 2 weeks before irradiation. After 14 days, results revealed that total body irradiation induced significant decreases in RBCs, WBCs and lymphocytes, as well as Glutathione (GSH) and zinc superoxide dismutase (Zn/SOD), splenocyte count, bone marrow lymphocyte count and viability. Tumor necrosis factor alpha (TNF-α) and interleukin 2 (IL-2) also recorded significant decrease while interleukin 6 (IL-6) and lipid peroxidation marker malondialdehde (MDA) in serum and spleen were conversely elevated. In irradiated animals receiving BMT and WGO, values of MDA in serum and tissue were significantly depressed as compared with the irradiated group, while lymphocytes, bone marrow viability percentage, splenocytes percentage, IL-2, IL-6 and GSH were significantly elevated. The curative action of WGO enforcing significant innate response could trigger and augment adaptive immune response by BMT, thus protecting immune system from radiation induced damage as well as oxidative stress.

Share and Cite:

Soliman, M. , Ashry, O. , Ahmed, M. and El-Naby, Y. (2015) Improvement of Hematopoietic and Immunologic Findings in Sublethal Gamma Irradiated Rats Treated with Bone Marrow Transplantation and Wheat Germ Oil. Journal of Immune Based Therapies, Vaccines and Antimicrobials, 4, 9-18. doi: 10.4236/jibtva.2015.42002.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Pourhomayoun, M., Fowler, M.L. and Jin, Z. (2014) Robustness Analysis of Sparsity Based Tumor Localization under Tissue Configuration Uncertainty. IEEE Signal Processing in Medicine and Biology Symposium (SPMB12), 3, 8-15.
[2] Sankaranarayanan, A. (2006) Analysis of Radiation-Associated Changes in Gene Expression Using Microarray Technology. The British Journal of Radiology, 26, 131.
[3] Maurya, D.K., Adhikari, S., Nair, C.K. and Devasagayam, P.A. (2007) DNA Protective Properties of Vanillian against γ-Radiation under Different Conditions Possible Mechanisms. Mutation Research, 7, 634-669.
[4] Ornoy, A. (2007) Embryonic Oxidative Stress as a Mechanism of Teratogenesis with Special Emphasis on Diabetic Embryopathy. Reproductive Toxicology, 7, 24-31.
[5] Bonadio, R.K., Loh, Y. and Pearce, W. (2005) Clinical Applications of Blood-Derived and Marrow-Derived Stem Cells for Nonmalignant Diseases. Journal of the American Medical Association, 299, 925-936.
[6] Atkins, H.L. and Freedman, M.S. (2013) Hematopoietic Stem Cell Therapy for Multiple Sclerosis: Top 10 Lessons Learned. Neurotherapeutics, 10, 68-76.
[7] Van Burik, J.A. and Weisdrof, C.G. (1999) Infectious Complications Following Unrelated Cord Blood Transplantation. Bailliere’s Clinical Infectious Diseases,92, 289-296.
[8] Cowan, M.M. (1999) Plant Products as Antimicrobial Agents. Clinical Microbiology Reviews, 12, 564-582.
[9] Singh, K., Parekh, I., Brown, S., Kao, T. and Mog, R. (2010) Tocopherol Succinate: Modulation of Antioxidant Enzymes and Oncogene Expression, and Hematopoietic Recovery. International Journal of Radiation Oncology, Biology, Physics, 79, 571-578.
[10] Jensen, M.K., Koh-Banerjee, P., Hu, F.B., Franz, M. and Sampson, L. (2004) Intakes of Whole Grains, Bran and Germ and the Risk of Coronary Heart Disease in Men. The American Journal of Clinical Nutrition, 80, 1492-1499.
[11] Lui, R.H. (2007) Whole Grain Phytochemicals and Health. Journal of Cereal Science, 46, 207-219.
[12] Traber, M.G. (1999) Vitamin E. In: Shils, M.E., Olson, J.A. and Shike, M., Eds., Modern Nutrition in Health and Disease, 10th Edition, Vol. 1, Williams & Wilkins, Baltimore, 347-362.
[13] Gelmeza, N., Kincal, N.S. and Yener, M.E. (2009) Optimization of Supercritical Carbon Dioxide Extraction of Antioxidants from Roasted Wheat Germ Based on Yield, Total Phenolic and Tocopherol Contents, and Antioxidant Activities of the Extracts. The Journal of Supercritical Fluids, 48, 217-224.
[14] Hargrove, H., Greenspan, P. and Hartle, D.K. (2014) Nutritional Significance and Metabolism of Very Long Chain Fatty Alcohols and Acids from Dietary Waxes. Experimental Biology and Medicine, 229, 215-226.
[15] Dacie, S.T. and Lewis, S.M. (1993) Practical Haematology. Chap. 5, ELBS and Churchill, Levingston, London, 37-47.
[16] Beutler, E., Duron, O. and Kelly, B.M. (1963) Improved Method for the Determination of Blood Glutathione. Journal of Laboratory and Clinical Medicine, 61, 882-888.
[17] Yoshioka, T., Kawada, K., Shimada, T. and Mori, M. (1979) Lipid Peroxidation in Maternal Cord Blood and Protective Mechanism against Activated Oxygen Toxicity in Blood. American Journal of Obstetrics and Gynecology, 135, 372-376.
[18] Chan, V.S. and Perlstein, L.D. (1987) Affinity Chromatographic Separation of Alpha-Fetoprotein Variants. Academic Press, New York, 71.
[19] Kaminska, J., Kowalska, M.M., Nowacki, M.P., Chwalinski, M.G., Rysinska, A. and Fuksiewicz, M. (2000) CRP, TNFα, IL-1ra, IL-6, IL-8 and IL-10 in Blood Serum of Colorectal Cancer Patients. Pathology Oncology Research, 6, 38-41.
[20] Aramachi, T. (1989) Japan’s Bioventures Today. Immuno-Biological Laboratories Company, Ltd., Japan, 370, 831.
[21] Esser, M.T., Bess, J.W., Suryanarayana, K., Chertova, E., Marti, D., Carrington, M., Arthur, L.O. and Lifson, J.D. (2001) Partial Activation and Induction of Apoptosis in CD4+ and CD8+ T Lymphocytes by Conformationally Authentic Noninfectious Human Immunodeficiency Virus Type 1. Journal of Virology, 75, 1152-1164.
[22] Sinai, M.R., Uma Devi, S. and Yadav, S.S. (1978) Radiation Protection of Bone Marrow Lymphocytes by 2-Mercapto-propionylglycine (MPG). Experientia, 34, 1627-1628.
[23] Takabatake, T., Nakamoto, G. and Menovsky, A.A. (1997) Strong Reduction of Quasiparticle Scattering Rate with Gap Formation in CeNiSn. Physical Review B, 56, 8277-8281.
[24] Sarkar, S.R., Singh, L.R., Uniyal, B.P. and Bhatnagar, V.S. (1988) Radioprotective Effects of Liv.52 and Tissue-Reduced Glutathione (GSH) in Experimental Rats. The Bombay Hospital Journal, 4, 41.
[25] Sredini, B., Albeck, M., Kazimmersky, G. and Shalet, F. (1992) The Immunomodulator AS101 Administrated Orally as a Radioprotective Agent. International Journal of Immunopharmacology, 14, 613-619.
[26] Paranich, V., Cherevko, O., Frolova, N. and Paranich, A. (2000) The Effect of Wheat Germ Oil on the Antioxidant System of Animals. Likars’ka Sprava, No. 2, 40-44.
[27] Reddy, B., Hirose, Y., Cohen, L., Simi, B., Cooma, I. and Rao, C. (2000) Preventive Potential of Wheat Bran Fractions against Experimental Colon Carcinogenesis: Implications for Human Colon Cancer Prevention. Cancer Research, 60, 4792-4797.
[28] Steel, R.G.D. and Torrie, J.H. (1980) Analysis of Covariance. In: Steel, R.G.D., Ed., Principles and Procedures of Statistics: A Biometrical Approach, McGraw-Hill, New York, 401-437.
[29] Gridley, D.S., Pecaut, M.J., Miller, G.M., Moyers, M.F. and Nelson, G.A. (2001) Dose and Dose Rate Effects of Whole-Body Gamma-Irradiation: II. Haematological Variables and Cytokines. In Vivo, 15, 209-216.
[30] Wikins, R.C., Wikinson, D., Maharaj, H.P., Bellier, P.V., Cybulski, M.B. and McLean, J.R. (2002) Differential Apoptotic Response to Ionizing Radiation in Subpopulations of Human White Blood Cells. Mutation Research/Genetic Toxicology and Environmental Mutagenesis, 513, 27-36.
[31] Zhang, D.H., Cohn, L., Ray, P., Bottomly, K. and Ray, A. (2010) Transcription Factor GATA-3 Is Differentially Expressed in Murine Th1 and Th2 Cells and Controls Th2-Specific Expression of the Interleukin-5 Gene. The Journal of Biological Chemistry, 272, 21597-21603.
[32] Abu-Sinna, G., Kafafy, Y.A., Nassar, A.Y. and Salman, M.A. (2005) Synergistic Effect of Bone Marrow Transplantation and Bradykinin Potentiating Factor Isolated from Venom on Thymus and Spleen of Sublethally Irradiated Guinea Pig. The Egyptian Journal of Radiation Science, 18, 249-255.
[33] Micke, O., Haidenberger, A., Auer, T., Egger, S., Seegenschmiedt, H.M., Hengster, P. and DeVries, A.F. (2005) Irradiation Causes Biphasic Neutrophilic Granulocyte Phagocytic Function. Strahlentherapie und Onkologie, 181, 313-318.
[34] Ashry, O.M., Hussein, E.M. and Salama, S.F. (2009) Boosting of Antioxidant Defense by Interferon-Alpha in Irradiated Bone Marrow Transplantation Rats. The Egyptian Journal of Radiation Science, 22, 19-33.
[35] Nunia, V., Sncheti, G. and Goyal, P.K. (2007) Protection of Swiss Albino Mice against Whole-Body Gamma Irradiation by Diltiazem. The British Journal of Radiology, 80, 77-84.
[36] Omaima, M., Maha, G., Neveen, H. and Manar, A. (2013) Immunostimulatory Role of Panax Ginseng in Irradiated Bone Marrow Transplanted Rats. International Journal of Academic Research, 5, 115-123.
[37] Zarybnicka, L., Vavrova, J., Havelek, R., Tichy, A., Pejchal, J. and Sinkorova, Z. (2013) Lymphocyte Subsets and Their H2AX Phosphorylation in Response to in Vivo Irradiation in Rats. International Journal of Radiation Biology, 89, 110-117.
[38] Chew, B. and Park, J. (2004) Carotenoid Action on the Immune Response. Journal of Nutrition, 134, 257S-261S.
[39] Ma, X.H., Guo, W., Liu, X.P., Yin, T., Jia, X., Xiong, J., Zhang, H.P. and Wang, L.J. (2010) Effect of 60Co γ Radiation on Mesenchymal Stem Cells (MSCs) Proliferation and Differentiation. African Journal of Microbiology Research, 4, 2161-2168.
[40] Gong, F.L. (2003) Medical Immunology. Science Press, Beijing, 238-248.
[41] Bass, H., Mossmann, T. and Strober, S. (1989) Evidence for Mouse Th1- and Th2-Like Helper T Cells in Vivo. The Journal of Experimental Medicine, 170, 1495-1511.
[42] Adkins, B., Ghanei, A. and Hamiton, K. (1993) Developmental Regulation of IL-4, IL-2 and IFN-γ Production by Murine Peripheral T Lymphocytes. The Journal of Immunology, 151, 6617-6621.
[43] Field, E.H., Rouse, T.M., Gao, Q. and Chang, B. (1997) Association between Enhanced Th2/Th1 Cytokine Profile and Donor T-Cell Chimerism Following Total Lymphoid Irradiation. Human Immunology, 52, 144-154.
[44] Han, S.K., Song, J.Y., Yun, Y.S. and Yi, S.Y. (2005) Gamma Irradiation Reduced IFN-Gamma Expression, STAT-1 Signal, and Cell-Mediated Immunity. Journal of Biochemistry and Molecular Biology, 35, 583-589.
[45] Chang, C.M., Limanni, A., Baker, W.H., Dobson, M.E., Kalinich, J.F. and Patchen, M.L. (1997) Sublethal Gamma Irradiation Increases IL-1α, IL-6, and TNF-α mRNA Levels in Murine Hematopoietic Tissues. Journal of Interferon & Cytokine Research, 17, 567-572.
[46] Petit-Frère, C., Capulas, E., Lyon, D., Norbury, C., Lowe, J., Clingen, P., Christopher, J. and Green, M. (2000) Apoptosis and Cytokine Release Induced by Ionizing or Ultraviolet B Radiation in Primary and Immortalized Human Keratinocytes. Carcinogenesis, 21, 1087-1095.
[47] Tsukimoto, M., Homma, T., Mutou, Y. and Kojima, S. (2009) 0.5 Gy Gamma Radiation Suppresses Production of TNF-Alpha through Up-Regulation of MKP-1 in Mouse Macrophage RAW264.7 Cells. Radiation Research, 171, 219-224.
[48] Cachaço, A.S., Carvalho, T., Santos, A.C., Igreja, C. and Fragoso, R. (2010) TNF-α Regulates the Effects of Irradiation in the Mouse Bone Marrow Microenvironment. PLoS ONE, 5, e8980.
[49] Krishna, A. and Kumar, A. (2005) Evaluation of Radioprotective Effect of Rajira (Amaranthus paniculatus) Extract in Swiss Albino Mice. Journal of Radiation Research, 46, 233-239.
[50] Saada, H.N., Said, U.Z. and Mahdy, A.M. (2003) Effectiveness of Aloe Vera on the Antioxidant Status of Different Tissues in Irradiated Rats. Die Pharmazie, 58, 929-931.
[51] Said, U.Z. (2004) Neuroprotective Properties of Rutin in Radiation-Induced Biochemical Disorders in Brain of Rats. Arab Journal of Nuclear Sciences and Applications, 37, 223-231.
[52] Berdan, S., Nguyen, A. and Hassanein, D. (2011) Robo 4 Cooperates with CXCR4 to Specify Hematopoietic Stem Cell Localization to Bone Marrow Niches. Cell Stem Cell, 8, 72-83.
[53] Wang, Q., Jiang, J.Y. and Xie, S.S. (2002) Determination of Doxycycline in Serum by High-Performance Liquid Chromatography. The Chinese Journal of Clinical Pharmacology, 3, 119-201.
[54] Nakamura, T., Good, R.A., Yasumizu, R., Inoue, S., Oo, M. M., Mamashima, Y. and Ikehara, S. (2004) Successful Liver Allografts in Mice by Combination with Allogenic Bone Marrow Transplantation. Proceedings of the National Academy of Sciences of the United States of America, 83, 4529-4532.
[55] Lee, W.Y., Kang, M.I., Oh, E.S., Oh, K.W., Han, J.H., Cha, B.Y., Lee, K.W., Son, H.Y., Kang, S.K. and Kim, C.C. (2002) The Role of Cytokines in the Changes in Bone Turnover Following Bone Marrow Transplantation. Osteoporosis International, 13, 62-68.
[56] Kishimoto, T., Taga, T. and Akira, S. (1994) Cytokine Signal Transduction. Cell, 76, 253-262.
[57] Tawara, I., Koyama, M. and Liu, C. (2010) Interleukin-6 Modulates Graft-Versus-Host Responses after Experimental Allogeneic Bone Marrow Transplantation. Clinical Cancer Research, 17, 77-88.
[58] Singh, D.K., Li, L. and Porter, T.D. (2006) Policosanol Inhibits Cholesterol Synthesis in Hepatoma Cells by Activation of AMP-Kinase. Journal of Pharmacology and Experimental Therapeutics, 318, 1020-1026.
[59] Brown, G.R. and Thiele, D.L. (2000) Enhancement of MHC Class I-Stimulated Alloresponses by TNF/TNF Receptor (TNFR)1 Interactions and of MHC Class II-Stimulated Alloresponses by TNF/TNFR2 Interactions. European Journal of Immunology, 30, 2900-2907.<2900::AID-IMMU2900>3.0.CO;2-P
[60] Atkinson, K. (1990) Chronic Graft-Versus-Host Disease. Bone Marrow Transpl., 5, 69-98.
[61] De Rooij, D.G., Van de Kant, H.J., Dol, R., Wagemaker, G. and Van Buul, P.P. (2002) Long-Term Effects of Irradiation before Adulthood on Reproductive Function in the Male Rhesus Monkey. Biology of Reproduction, 66, 486-494.
[62] Ashry, O.M. and Hussein, E.M. (2007) Radioprotective Potency of Ginsengon on Some Haematopoeitic and Physiological Parameters in Irradiated Rats. The Egyptian Journal of Radiation Science, 20, 365-383.
[63] Adaramoye, O. A., Okiti, O. O. and Farombi, E. O. (2010) Dried Fruit Extract from Xylopia aethiopica (Annonaceae) Protects Wistar Albino Rats from Adverse Effects of Whole Body Radiation. Experimental and Toxicologic Pathology, 63, 635-643.
[64] Vinod, M., Jain, P., Verma, H., Kumar Gupta S., Sharma, V. and Thakur, R. (2012) An Overview on Natural Treatment of Systemic Lupus Erythematosus. Asian Journal of Pharmacy and Life Science, 2, 2231-4423.
[65] Zeinab, A., Khadiga, S., Abdel-Razik, H. and Eman, E. (2010) Effect of Carrot and Wheat Germ Oil Supplementation on Antioxidant Status of Rats Exposed to Benzene. Polish Journal of Food and Nutrition Sciences, 60, 175-181.
[66] Ibrahim, A.H., Osama, A., Samia. A. and Aziza, M. (2011) Evaluation of Radio Protective Effects of Wheat Germ Oil in Male Rats. Journal of American Science, 7, 664-673.
[67] Ehrenfeld, M., Blank, M., Shoenfeld, Y. and Hidvegi, M. (2001) AVEMAR (a New Benzoquinone-Containing Natural Product) Administration Interferes with the Th2 Response in Experimental SLE and Promotes Amelioration of the Disease. Lupus, 10, 622-627.
[68] Hidvegi, M., Raso, E., Tomoskozi-Farkas, R., Lapis, K. and Szende, B. (1999) Effect of AVEMAR on the Immune Response of Mice. Immunopharmacology, 41, 183-186.
[69] Glynn, R.J., Ridker, P.M., Goldhaber, S.Z., Zee, R.Y. and Buring, J.E. (2007) Effects of Random Allocation to Vitamin E Supplementation on the Occurrence of Venous Thromboembolism: Report from the Women’s Health Study. Circulation, 116, 1497-1503.
[70] Huang, Z.R., Lin, Y.K. and Fang, J.Y. (2009) Biological and Pharmacological Activities of Squalene and Related Compounds: Potential Uses in Cosmetic Dermatology. Molecules, 14, 540-554.
[71] Balk, B., Chung, M., Lichtenstein, A., Chew, P., Kupelnick, B., Lawrence, A., DeVine, D. and Lau, J. (2004) Effects of Omega-3 Fatty Acids on Cardiovascular Risk Factors and Intermediate Markers of Cardiovascular Disease. Immunopharmacology, 10, 36-44.
[72] Attila, S., Robert, C., Michail, I., Henry, D. and Allen, I. (2001) Nonlinear Behavior of Sinusoidally Forced Pyloric Pacemaker Neurons. Journal of Neurophysiology, 85, 1623-1638.
[73] Van Poppel, G. and Van den Berg, H. (1997) Vitamins and Cancer. Cancer Letters, 114, 195-202.
[74] Lee, I.M., Cook, N.R. and Gaziano, J.M. (2005) Vitamin E in the Primary Prevention of Cardiovascular Disease and Cancer: The Women’s Health Study: A Randomized Controlled Trial. JAMA, 294, 56-65.
[75] Sies, H., Stahl, W. and Sundquist, A. (1992) Antioxidant Functions of Vitamins. Vitamins E and C, Beta-Carotene, and Other Carotenoids. Annals of the New York Academy of Sciences, 669, 7-20.

Copyright © 2022 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.