The Possible Mechanisms Involved in the Protection Strategies against Radiation-Induced Cellular Damage by Carnitines


There is constant low level background radiation from the cosmos but in certain situation the body may be subjected to increased acute or chronic exposure from other sources. This occurs in situations such as radiation accidents, medical use and could possibly occur in military/terrorist incident. Dependent on the type, strength of the actual source, degree of exposure and type of radiation different strategies may be employed to reduce damage to the body tissues. A number of pharmacological agents such as peroxisome proliferator-activated receptor (PPAR) gamma agonists, diltiazem, amifostine and palifermin as well as antioxidants and metabolic compounds have been shown to be effective in preventing and also in reducing the long-term damage of the exposure of the living cells to radiation. The major drawback of synthetic (pharmacological) compounds has been that they are highly toxic at the optimum protective dose. Studies have shown that various endogenously found compounds such as L-carnitine, and its derivative acetyl-L-carnitine, are able to protect tissues and organs against various forms of toxic insult including radiation damage. The radiation-induced chronic injury may also be counteracted by other metabolic compounds with amine groups and antioxidant properties similar to the carnitines such as cysteine, 3,3’-diindolylmethane (DIM) and N-acetylcysteine. This review discuses the radioprotective compounds as well as the potential mechanism of cellular protection against radiation by carnitines and other compounds.

Share and Cite:

Virmani, A. and Diedenhofen, A. (2015) The Possible Mechanisms Involved in the Protection Strategies against Radiation-Induced Cellular Damage by Carnitines. International Journal of Clinical Medicine, 6, 71-80. doi: 10.4236/ijcm.2015.62011.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Laterjet, R. and Ephrati, E. (1948) Influence protectrice de certaines substance contrel’ inactivationd’ um bacteriophage par les rayons X. Comptes Rendus des Séances de la Société de Biologie et de Ses Filiales, 142, 497-499
[2] Joshi, Y., Jadhav, T. and Kadam, V. (2010) Radioprotective-A Pharmacological Intervention for Protection against Ionizing Radiations: A Review. The Internet Journal of Internal Medicine, 8, 2.
[3] Hosseinimehr, S.J. (2007) Trends in the Development of Radioprotective Agents. Drug Discovery Today, 12, 794-805.
[4] Weiss, J.F. and Landauer, M.R. (2003) Protection against Ionizing Radiation by Antioxidant Nutrients and Phytochemicals. Toxicology, 189, 1-20.
[5] Sugahara, T., Tanaka, Y., Nagata, H., Tanaka, T. and Kano, E. (1970) Radiation Protection by 2-Mercaptopropiony-lglycine. Proceedings of the International Symposium on Thiola, Osaka, 267-272.
[6] Yuhas, J.M. (1980) Active versus Passive Absorption Kinetics as the Basis for Selective Protection of Normal Tissues by S-2-(3-Aminopropylamino)-Ethylphosphorothioic Acid. Cancer Research, 40, 1519-1524.
[7] Nunia, V. and Goyal, P.K. (2004) Prevention of Gamma Radiation Induced Anaemia in Mice by Diltiazem. Journal of Radiation Research, 45, 11-17.
[8] Maier, P., Wenz, F. and Herskind, C. (2014) Radioprotection of Normal Tissue Cells. Strahlentherapie Und Onkologie, 190, 745-752.
[9] Kuntic, V.S., Stankovic, M.B., Vujic, Z.B., Brboric, J.S. and Uskokovic-Markovic, S.M. (2013) Radioprotectors—The Evergreen Topic. Chemistry & Biodiversity, 10, 1791-1803.
[10] Citrin, D., Cotrim, A.P., Hyodo, F., Baum, B.J., Krishna, M.C. and Mitchell, J.B. (2010) Radioprotectors and Mitigators of Radiation-Induced Normal Tissue Injury. Oncologist, 15, 360-371.
[11] Weiss, J.F. and Landauer, M.R. (2003) Protection against Ionizing Radiation by Antioxidant Nutrients and Phytochemicals. Toxicology, 189, 1-20.
[12] Jagetia, G.C. (2007) Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation. Journal of Clinical Biochemistry and Nutrition, 40, 74-81.
[13] Virmani, A. and Binienda, Z. (2004) Role of Carnitine Esters in Brain Neuropathology. Molecular Aspects of Medicine, 25, 533-549.
[14] Virmani, A., Pinto, L., Binienda, Z. and Ali, S. (2013) Food, Nutrigenomics, and Neurodegeneration-Neuroprotection by What You Eat! Molecular Neurobiology, 48, 353-362.
[15] Marzo, A., Arrigoni Martelli, E., Mancinelli, A., Cardace, G., Corbelletta, C., Bassani, E. and Solbiati, M. (1991) Protein Binding of L-Carnitine Family Components. European Journal of Drug Metabolism and Pharmacokinetics, Special Issue III, 364-368.
[16] Baker, H., Frank, O., De Angelis, B. and Baker, E.R. (1993) Absorption and Excretion of L-Carnitine during Single or Multiple Dosing in Humans. International Journal for Vitamin and Nutrition Research, 63, 22-26.
[17] Rebouche, C.J. (1986) Recent Advances in Carnitine Biosynthesis and Transport. In: Borum, P.R., Ed., Clinical Aspects of Human Carnitine Deficiency, Pergamon, New York, 1-15.
[18] Brass, E.P. (1992) Carnitine Transport. In: Ferrari, R., DiMauro, S. and Sherwood, G., Eds., L-Carnitine and Its Role in Medicine: From Function to Therapy, Academic Press Limited, London, 21-36.
[19] Virmani, M.A., Rossi, S., Conti, R., Spadoni, A., Arrigoni-Martelli, E. and Calvani, M. (1996) Structural, Metabolic and Ionic Requirements for the Uptake of L-Carnitine by Primary Rat Cortical Cells. Pharmacological Research, 33, 19-27.
[20] Kuwajima, M., Kono, N., Horiuchi, M., Imamura, Y., Ono, A., Inui, Y., Kawata, S., Koizumi, T., Hayakawa, J., Saheki, T., et al. (1991) Animal Model of Systemic Carnitine Deficiency: Analysis in C3H-H-2 Strain of Mouse Associated with Juvenile Visceral Steatosis. Biochemical and Biophysical Research Communications, 174, 1090-1094.
[21] Khan, H.A. and Alhomida, A.S. (2011) A Review of the Logistic Role of L-Carnitine in the Management of Radiation Toxicity and Radiotherapy Side Effects. Journal of Applied Toxicology, 31, 707-713.
[22] Dokmeci, D., Akpolat, M., Aydogdu, N., Uzal, C., Doganay, L., Turan, F.N. and Mansour, H.H. (2006) The Protective Effect of L-Carnitine on Ionizing Radiation-Induced Free Oxygen Radicals. Scandinavian Journal of Laboratory Animal Science, 33, 75-83.
[23] Altas, E., Ertekin, M.V., Gundogdu, C. and Demirci, E. (2006) L-Carnitine Reduces Cochlear Damage Induced by Gamma Irradiation in Guinea Pigs. Annals of Clinical and Laboratory Science, 36, 312-318.
[24] Ucüncü, H., Ertekin, M.V., Yorük, O., Sezen, O., Ozkan, A., Erdogan, F., Kiziltunc, A. and Gündogdu, C. (2006) Vitamin E and L-Carnitine, Separately or in Combination, in the Prevention of Radiation-Induced Oral Mucositis and Myelosuppression: A Controlled Study in a Rat Model. Journal of Radiation Research, 47, 91-102.
[25] Kocer, I., Taysi, S., Ertekin, M.V., Karslioglu, I., Gepdiremen, A., Sezen, O. and Serifoglu, K. (2007) The Effect of L-Carnitine in the Prevention of Ionizing Radiation-Induced Cataracts: A Rat Model. Graefe’s Archive for Clinical and Experimental Ophthalmology, 245, 588-594.
[26] Sezen, O., Ertekin, M.V., Demircan, B., Karslioglu, I., Erdogan, F., Kocer, I., Calik, I. and Gepdiremen, A. (2008) Vitamin E and L-Carnitine, Separately or in Combination, in the Prevention of Radiation-Induced Brain and Retinal Damages. Neurosurgical Review, 31, 205-213.
[27] Topcu-Tarladacalisir, Y., Kanter, M. and Uzal, M.C. (2009) Role of L-Carnitine in the Prevention of Seminiferous Tubules Damage Induced by Gamma Radiation: A Light and Electron Microscopic Study. Archives of Toxicology, 83, 735-746.
[28] Kanter, M., Topcu-Tarladacalisir, Y. and Parlar, S. (2010) Antiapoptotic Effect of L-Carnitine on Testicular Irradiation in Rats. Journal of Molecular Histology, 41, 121-128.
[29] Caloglu, M., Yurut-Caloglu, V., Durmus-Altun, G., Oz-Puyan, F., Ustun, F., Cosar-Alas, R., Saynak, M., Parlar, S., Turan, F.N. and Uzal, C. (2009) Histopathological and Scintigraphic Comparisons of the Protective Effects of L-Carnitine and Amifostine against Radiation-Induced Late Renal Toxicity in Rats. Clinical and Experimental Pharmacology and Physiology, 36, 523-530.
[30] Cosar, R., DurmusAltun, G., Oz Puyan, F., Saynak, M., Ibis, K., Ozen, A., Bayir-Angin, G., Ustun, F., Denizli, B., Parlar, S., Caloglu, M., Yurut-Caloglu, V., Uzal, M.C. and Kocak, Z. (2011) Protective Role of Carnitine against Radiation-Induced Kidney Damage in Infant Rats: Scintigraphic and Histopathologic Evaluation. Radiotherapy and Oncology, 98, S20-S21.
[31] Caloglu, M., Caloglu, V.Y., Yalta, T., Yalcin, O. and Uzal, C. (2012) The Histopathological Comparison of L-Carnitine with Amifostine for Protective Efficacy on Radiation-Induced Acute Small Intestinal Toxicity. Journal of Cancer Research and Therapeutics, 8, 260-265.
[32] Akpolat, M., Gulle, K., Topcu-Tarladacalisir, Y., Safi Oz, Z., Bakkal, B.H., Arasli, M. and Ozel Turkcu, U. (2013) Protection by L-Carnitine against Radiation-Induced Ileal Mucosal Injury in the Rat: Pattern of Oxidative Stress, Apoptosis and Cytokines. International Journal of Radiation Biology, 89, 732-740.
[33] Mansour, H.H. (2006) Protective Role of Carnitine Ester against Radiation-Induced Oxidative Stress in Rats. Pharmacological Research, 54, 165-171.
[34] Babicová, A., Havlínová, Z., Hroch, M., Rezácová, M., Pejchal, J., Vávrová, J. and Chládek, J. (2013) In Vivo Study of Radioprotective Effect of NO-Synthase Inhibitors and Acetyl-L-Carnitine. Physiological Research, 62, 701-710.
[35] Jagetia, G.C., Baliga, M.S., Aruna, R., Rajanikant, G.K. and Jain, V. (2003) Effect of Abana (a Herbal Preparation) on the Radiation-Induced Mortality in Mice. Journal of Ethnopharmacology, 86, 159-165.
[36] Singh, V.K., Shafran, R.L., Jackson III, W.E., Seed, T.M. and Kumar, K. (2006) Induction of Cytokines by Radioprotective Tocopherol Analogs. Experimental and Molecular Pathology, 81, 55-61.
[37] Yilmaz, S. and Yilmaz, E. (2006) Effects of Melatonin and Vitamin E on Oxidative-Antioxidative Status in Rats Exposed to Irradiation. Toxicology, 222, 1-7.
[38] Fan, S., Meng, Q., Xu, J., Jiao, Y., Zhao, L., Zhang, X., Sarkar, F.H., Brown, M.L., Dritschilo, A. and Rosen, E.M. (2013) DIM (3,3'-Diindolylmethane) Confers Protection against Ionizing Radiation by a Unique Mechanism. Proceedings of the National Academy of Sciences of the United States of America, 110, 18650-18655.
[39] Mansour, H.H., Hafez, H.F., Fahmy, N.M. and Hanafi, N. (2008) Protective Effect of N-Acetylcysteine against Radiation Induced DNA Damage and Hepatic Toxicity in Rats. Biochemical Pharmacology, 75, 773-780.
[40] Sert, C., Celik, M.S., Akdag, Z., Ketani, M.A. and Nergiz, Y. (2000) The Radioprotective Effect of Vitamins C, E and Vitamin E + Glutathione on the Small Intestine and the Thyroid Gland in Rats Irradiated with X Rays. Turkish Journal of Medical Sciences, 30, 417-425.
[41] Vijayalaxmi, Reiter, R.J., Tan, D.X., Herman, T.S. and Thomas Jr., C.R. (2004) Melatonin as a Radioprotective Agent: A Review. International Journal of Radiation Oncology*Biology*Physics, 59, 639-653.
[42] Prasad, K.N. (2005) Rationale for Using Multiple Antioxidants in Protecting Humans against Low Doses of Ionizing Radiation. British Journal of Radiology, 78, 485-492.
[43] Bhartiya, U.S., Raut, Y.S., Joseph, L.J., Hawaldar, R.W. and Rao, B.S. (2008) Evaluation of the Radioprotective Effect of Turmeric Extract and Vitamin E in Mice Exposed to Therapeutic Dose of Radioiodine. Indian Journal of Clinical Biochemistry, 23, 382-386.
[44] Samarth, R.M., Panwar, M., Kumar, M., Soni, A., Kumar, M. and Kumar, A. (2008) Evaluation of Antioxidant and Radical-Scavenging Activities of Certain Radioprotective Plant Extracts. Food Chemistry, 106, 868-873.
[45] Soyal, D., Jindal, A., Singh, I. and Goyal, P.K. (2007) Modulation of Radiation-Induced Biochemical Alterations in Mice by Rosemary (Rosemarinus officinalis) Extract. Phytomedicine, 14, 701-705.
[46] Sener, G., Kabasakal, L., Atasoy, B.M., Erzik, C., Velioglu-Ogünc, A., Cetinel, S., Gedik, N. and Yegen, B.C. (2006) Ginkgo Biloba Extract Protects against Ionizing Radiation-Induced Oxidative Organ Damage in Rats. Pharmacological Research, 53, 241-252.
[47] Azzam, E.I., Jay-Gerin, J.P. and Pain, D. (2012) Ionizing Radiation-Induced Metabolic Oxidative Stress and Prolonged Cell Injury. Cancer Letters, 327, 48-60.
[48] Cox, M.M. and Battista, J.R. (2005) Deinococcus radiodurans—The Consummate Survivor. Nature Reviews Microbiology, 3, 882-892.
[49] Daly, M.J. (2009) A New Perspective on Radiation Resistance Based on Deinococcus radiodurans. Nature Reviews Microbiology, 7, 237-245.
[50] Virmani, M.A., Caso, V., Spadoni, A., Russo, F., Rossi, S. and Gaetani, F. (2001) The Action of Acetyl-l-Carnitine on the Neurotoxicity Evoked by Amyloid Fragments on Primary Rat Cortical Neurones. Annals of the New York Academy of Sciences, 939, 162-178.
[51] Stadtman, E.R. (2006) Protein Oxidation and Aging. Free Radical Research, 40, 1250-1258.
[52] Virmani, M.A., Bisselli, R., Spadoni, A., Rossi, S., Corsico, N., Calvani, M., Fattorossi, A., De Simone, C. and Arrigoni-Martelli, E. (1995) Protective Actions of L-Carnitine and Acetyl-L-Carnitine on the Neurotoxicity Evoked by Mitochondrial Uncoupling or Inhibitors. Pharmacological Research, 32, 383-389.
[53] Rezvani, M. (2008) Amelioration of the Pathological Changes Induced by Radiotherapy in Normal Tissues. Journal of Pharmacy and Pharmacology, 60, 1037-1048.
[54] Zhao, W. and Robbins, M.E. (2009) Inflammation and Chronic Oxidative Stress in Radiation-Induced Late Normal Tissue Injury: Therapeutic Implications. Current Medicinal Chemistry, 16, 130-143.
[55] Stone, H.B., McBride, W.H. and Coleman, C.N. (2002) Modifying Normal Tissue Damage Postirradiation. Report of a Workshop Sponsored by the Radiation Research Program, National Cancer Institute, Bethesda, Maryland, 6-8 September 2000. Radiation Research, 157, 204-223.[0204:MNTDP]2.0.CO;2
[56] Gramignano, G., Lusso, M.R., Madeddu, C., Massa, E., Serpe, R., Deiana, L., Lamonica, G., Dessì, M., Spiga, C., Astara, G., Macciò, A. and Mantovani, G. (2006) Efficacy of L-Carnitine Administration on Fatigue, Nutritional Status, Oxidative Stress, and Related Quality of Life in 12 Advanced Cancer Patients Undergoing Anticancer Therapy. Nutrition, 22, 136-145.

Copyright © 2020 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.