ABSTRACT Various approaches have been developed for diminishing the effects of radiation on normal tissues or enhancing tumor cell killing by ionizing radiation. Recently, there has been an increase in the interest in research on synthetic and/or natural radioprotective agents. An important potential use for these agents is to modify and improve the outcome of radiation therapy. The aim of this study was to examine the potential radioprotective role and antioxidant potency of the novel synthetic anticancer agent, quinoline sulfonamide (PIQSA) against tissue injury and oxidative stress induced by the exposure to gamma radiation and/or incidence of cancer in experimental animals. Mice (normal and bearing solid tumors) administered PIQSA (0.350 mg/kg body weight ip. three times a week for 21 days. At the last week of 30 days experimental period, an animal group was subjected to three successive doses of γ-radiation each of 2 Gy; another group was treated with combined administration of PIQSA 20 minutes before γ-irradiation. Some biochemical parameters (LPx, GSH, SOD, and CAT in liver homogenates, also plasma lipid profile (total lipids, total cholesterol, total triglycerides (TG), HDLc and LDLc were measured. To examine any adverse effect which could be attained by chemical treatment, liver enzymes (AST, ALT), and kidney function (creatinine and urea) were estimated in blood plasma, in addition to examination of some haematological indexes. The results indicated that the deleterious effects due to exposure to γ-radiation, and/or incidence of cancer on most of the estimated parameters could be controlled to a certain extent by administration of PIQSA to animals prior to irradiation. The results also confirmed that there were no significant adverse effects on mice due to the treatment with this chemical compound.
Cite this paper
nullR. Yousri, E. Noaman, O. Shawi, N. Fahmy and M. Ghazy, "Evaluation of Anti-Oxidant Status and Radioprotective Activity of a Novel Anti-Cancer Drug in Mice," Journal of Cancer Therapy, Vol. 2 No. 5, 2011, pp. 616-628. doi: 10.4236/jct.2011.25083.
 W. P. Hogle, “Cytoprotective Agents Used in the Treatment of Patients with Cancer,” Seminars in Oncology Nursing, Vol. 23, No. 3, 2007, pp. 213-224.
 E. J. Hall, “Radiotherapy for the Radiologist,” 5th Edition, Williams and Wilkins, Philadelphia, 2000.
 N. Rajapakse, M. M. Kim, E. Mendis and S. K. Kim, ‘Inhibition of Free Radical Mediated Oxidation of Cellular Biomolecules by Carboxylated Chitoologosaccharides,” Bioorganic & Medicinal Chemistry, Vol. 15, No. 2, 2007, pp. 997-1003. doi:10.1016/j.bmc.2006.10.030
 V. R. Tandon, S. Sharma, A. Mahajan and G. H. Bardi, “Oxidative Stress: A Novel Strategy in Cancer Treatment,” JK Science, Vol. 7, No. 1, 2005, p. 48.
 M. A. El-Missiry, T. A. Fayed, M. R. El-Sawy and A. A. El-Sayed, “Ameliorative Effect of Melatonin against Gamma-Irradiation-Induced Oxidative Stress and Tissue Injury,” Ecotoxicology and Environmental Safety, Vol. 66 No. 2, 2007, pp. 278-286.
 J. A. Jalal, K. A. Albuseeda, T. A. Kumosani, K. O. Aboulnaja and M. F. Elshal, “Elucidation of the Determinant Factors Affecting Camels’Health in Some Regions of Saudi Arabia: A Biochemical, Histological, and Toxicological Study,” Journal of King Abdulaziz University, Vol. 22, No. 1, 2010, pp. 225-238.
 G. C. Jagetia, “Radioprotective Potential of Plants and Herbs against the Effects of Ionizing Radiation,” Journal of Clinical Biochemistry and Nutrition, Vol. 40, No. 2, 2007, pp. 74-81. doi:10.3164/jcbn.40.74
 D. K. Chandrasekharan, T. V. Kagiya and C. K. K. Nair, “Radiation Protection by 6-Palmitoyl Ascorbic Acid-2-Glucoside: Studies on DNA Damage in Vitro, ex Vivo, in Vivo and Oxidative Stress in Vivo,” Journal of Radiation Research, Vol. 50, No. 3, 2009, pp. 203-212.
 D. K. Maurya, T. P. A. Devasagayam and C. K. Nair, “Some Novel Approaches for Radiation Protection and the Beneficial Effect of Natural Products,” Indian Journal of Experimental Biology, Vol. 44, 2006, pp. 93-114.
 M. M. Ghorab, F. A. Ragab, E. Noaman, H. I. Heiba and E. M. El-Hossary, “Synthesis of Some Novel Quinolines and Pyrimido [4,5-b] Quinolines Bearing a Sulfonamide Moiety as Potential Anticancer and Radioprotective Agents,” Arzneimittelforschung, Vol. 57, No. 12, 2007, pp. 795-803.
 T. Yoshioka, K. Kawada, T. Shimada and M. Mori, “Lipid Peroxidation in Maternal and Cord Blood and Protective Mechanism against Activated Oxygen Toxicity in the Blood,” American Journal of Obstetrics & Gynecology, Vol. 135, No. 3, 1979, pp. 372-376.
 E. Beutler, O. Duron and B. M. Kelly, “Improved Method for the Determination of Blood Glutathione,” Journal of Laboratory and Clinical Medicine, Vol. 61, 1963, pp. 882-888.
 M. Minami and M. Yoshikawa, “A Simplified Assay Method of Superoxide Dismutase Activity for Clinical Use,” Clinica Chimica Acta, Vol. 92, No. 3, 1979, pp. 337-342. doi:10.1016/0009-8981(79)90211-0
 L. H. Johansson and L. A. H. Borg, “A spectrophotometric Method for Determination of Catalase Activity in Small Tissue Samples,” Analytical Biochemistry, Vol. 174, No. 1, 1988, pp. 331-336.
 J. A. Knight, S. Anderson and J. M. Rawle, “Estimation of Total Lipids in Serum and Tissues,” Clinical Chemistry, Vol. 18, No. 3, 1972, pp. 199-202.
 D. Watson, “Simple Method for the Determination of Serum Cholesterol,” Clinica Chimica Acta, Vol. 5, No. 5, 1960, pp. 637-643. doi:10.1016/0009-8981(60)90004-8
 P. Fossati and L. Principe, “Serum Triglycerides Determined Calorimetrically with an Enzyme That Produce Hydrogen Peroxide,” Clinical Chemistry, Vol. 28 No. 10, 1982, pp. 2077-2080.
 G. R. Warnick, J. Benderson and J. J. Albers, “Dextran-Sulfate-Mg2+ Precipitation Procedure for Quantitation of High Density Lipoprotein Cholesterol,” Clinical Chemistry, Vol. 28, No. 6, 1982, pp. 1397-1388.
 H. U. Bergmenyer, “Methods of Enzymatic Analysis,” 3rd Edition, Vch Publisher, New York, 1985, pp. 154-160.
 S. Reitman and S. Frankel, “A Colorimetric Method for the Determination of Glutamic Oxalacetic and Glutamic Pyruvic Transaminases,” American Journal of Clinical Pathology, Vol. 28, No. 1, 1957, pp. 56-63.
 R. J. Henry, D. C. Cannon and W. Winkelman, “Clinical Chemistry Principles and Techniques,” 11th Edition, Happer and Row Publishers, New York, 1974.
 C. J. Patton and S. R. Crouch , “Spectrophotometric and Kinetics Investigation of the Berthelot Reaction for the Determination of Urea,” Analytical Chemistry, Vol. 49, No. 3, 1977, pp. 464-469. doi:10.1021/ac50011a034
 J. V. Daci and S. M. Lewis, “Practical Haematology,” 5th Edition, Churchill Living Stone, London, 1975.
 R. G. Steel and T. H. Torrie, “Principles and Procedures of Statistics,” 2nd Edition, McCraw-Hill Book Co., New Delhi, 1980, p. 683.
 E Cicek, M. Yildiz, N. Delibas and S. Bah?eli, “The Effects of 201Tl Myocardial Perfusion Scintigraphy Studies on Oxidative Damage in Patients,” West Indian Medical Journal, Vol. 58, No. 1, 2009, pp. 50-53.
 H. Bartsch and J. Nair, “Potential Role of Lipid Peroxidation Derived DNA Damage in Human Colon Carcinogenesis: Studies on Exocyclic Base Adducts As Stable Oxidative Stress Markers,” Cancer Detection and Prevention, Vol. 26, No. 4, 2002, pp. 308-312.
 A. Valavanidis, T. Vlahoyianni and K. Fiotakis, “ Comparative Study of the Formation of Oxidative Damage Marker 8-hydroxy-2’-deoxyguanosine (8-OHdG) Adduct from the Nucleoside 2’-deoxyguanosine by Transition Metals and Suspensions of Particulate Matter in Relation to Metal Content and Redox Reactivity,” Free Radical Research, Vol. 39, No. 10, 2005, pp. 1071-1081.
 M. Koc, S. Taysi, M. E. Buyukokuroglu and N. Bakan, “The Effect of Melatonin against Oxidative Damage during Total-Body Irradiation in Rats,” Radiation Research, Vol. 160, No. 2, 2003, pp. 251-255. doi:10.1667/3034
 M. Sri Balasubashini, S. Karthigayan, S. T. Somasundaram, T. Balasubramanian, V. Viswanathan, P. Raveendran and V. P. Menon, “Fish Venom (Pterios volitans) Peptide Reduces Tumor Burden and Ameliorates Oxidative Stress in Ehrlich’s Ascites Carcinoma Xenografted Mice,” Bioorganic & Medicinal Chemistry Letters, Vol. 16, No. 24, 2006, pp. 6219-6225.
 M. Gupta, U. K. Mazumder, R. S. Kumar and T. S. Kumar, “Antitumor Activity and Antioxidant Role of Bauhinia Racemosa against Ehrlich Ascites Carcinoma in Swiss Albino Mice,” Acta Pharmacologica Sinica, Vol. 25, No. 8, 2004, pp. 1070-1076.
 L. Gibellini, M. Pinti, M. Nasi, S. De Biasi, E. Roat, L. Bertoncelli and A. Cossarizza, “Interfering with ROS Metabolism in Cancer Cells: The Potential Role of Quercetin,” Cancers, Vol. 2, No. 2, 2010, pp. 1288-1311.
 C. M. Panthak, P. K. Avti, S. Kumar, K. L. Khanduja and S. C. Sharma, “Whole Body Exposure to low Gamma Radiation Promotes Kidney Antioxidant Status in Balb/C Mice,” Journal of Radiation Research, Vol. 48, No. 2, 2007, pp. 113-120. doi:10.1269/jrr.06063
 P. K. Avti, C. M. Pathak, S. Kumar, G. Kaushik, T. Kaushik, A. Farooque, K. L. Khanduja and S. C. Sharma. “Low Doses Gamma-Irradiation Differentially Modulates Antioxidant Defense in Liver and Lungs of Balb/C Mice,” Journal of Radiation Research, Vol. 81, No. 12, 2005, pp. 901-910.
 J. Navarro, E. Obrador, J. Carretero, I. Petschen, J. Avino, P. Perez and J. M. Estrela, “Changes in Glutathione Status and the Antioxidant System in Blood and in Cancer Cells Associate with Tumour Growth in Vivo,” Free Radical Biology & Medicine, Vol. 26, 1999 pp. 410-418.
 Y. Sun, L. W .Oberley, J. H. Elwell and E. Sierra-Rivera, “Antioxidant Enzyme Activities in Normal And Transformed Mice Liver Cells,” International Journal of Cancer, Vol. 44, No. 6, 1989, pp. 1028-1033.
 Naveena, B. K. Bharath and S. Subramanian, “Antitumor Activity of Aloe Vera against Ehrlich Ascitis Carcinoma (EAC) in Swiss Albino Mice,” International Journal of Pharma and Bio Sciences, Vol. 2, No. 2, 2011, pp. 400-409
 Y .Ohta, M. Kongo-Nishimura, T. Matsura, K. Yamada, A. Kitagawa and T. Kishikawa, “Melatonin Prevents Disruption of Hepatic Reactive Oxygen Species Metabolism in Rats Treated with Carbon Tetrachloride,” Journal of Pineal Research, Vol. 36, No. 1, 2004, pp. 10-17.
 C. Kalpana and V. P. Menon, “Modulatory Effects of Curumin on Lipid Peroxidation and Antioxidant Status during Nicotine Induced Toxicity,” Polish Journal of Pharmacology, Vol. 56, No. 5, 2004, p. 581.
 H. N. Saada, U. Z. Said and A. M. Mahdy, “Effectiveness of Aloe Vera on the Antioxidant Status of Different Tissues in Irradiated Rats,” Pharmazie, Vol. 58, No. 2, 2003, pp. 929-931.
 U. Z. Said, K. S. Azab and S. M. Soliman, “Cardioprotective Role of Garlic (Allium sativum) on Oxidative Stress Induced by Gamma Radiaiton Exposure,” Isotope and Radiation Research, Vol. 36, No. 3, 2004, pp. 465-479.
 T. Zima, L. Fialova, O. Mestek, M. Janebova, J. Crkovska, I. Malbohan, S. Stipek, L. Mikulikova and P. Popov, “Oxidative Stress, Metabolism of Ethanol and Alcohol-Related Diseases,” Journal of Biomedical Science, Vol. 8, No. 1, 2001, pp. 59-70.
 P. S. Patel, M. H. Shah, F. P. Jha, G. N. Raval, R. M. Rawal, M. M. Patel, J. B. Patel and D. D. Patel, “Alterations in Plasma Lipid Profile Patterns in Head and Neck Cancer and Oral Precancerous Conditions,” Indian Journal of Cancer, Vol. 41, No. 1, 2004, pp. 25-31.
 A. Bielecka-Dabrowa, S. Hannam, J. Rysz and M. Banach, “Malignancy-Associated Dyslipidemia,” Open Cardiovascular Medicine Journal, Vol. 5, 2011, pp. 35-40. doi:10.2174/1874192401105010035
 S. K. Ardestani1, M. M. Janlow, A. Kariminia and Z. Tavakoli, “Effect of Cimetidine and Ranitidine on Lipid Profile and Lipid Peroxidation in γ-Irradiated Mice,” Acta Medica Iranica, Vol. 42, No. 3, 2004, pp. 198-204.
 L. Ashakumary and P. L. Vijayammal, “Effect of Nicotine on Lipoprotein Metabolism in Rats,” Lipids, Vol. 32, No. 3, 1997, pp. 311-315. doi:10.1007/s11745-997-0038-8
 P. Hermanik and L. H. Sobin, “International Union against Cancer (UICC): TNM Classification of Malignant Tumours, Head and Neck Tumours,” 4th Edition, Springer, Geneva, 1987.
 M. A. Choi, B. S. Kim and R. Yu, “Serum Antioxidative vitamin Levels and Lipid Peroxidation in Gastric Carcinoma Patients,” Cancer Letters, Vol. 136, No. 1, 1999, pp. 89-93. doi:10.1016/S0304-3835(98)00312-7
 O. E. Odeleye, C. D. Eskelson, S. I. Mufti and R. R. Watson, “Vitamin E Inhibition of Lipid Peroxidation and Ethanol-Mediated Promotion of Esophageal Tumorigenesis,” Nutrition and Cancer, Vol. 17, No. 3, 1992, pp. 223-234. doi:10.1080/01635589209514191
 D. Applebaum-Bowden, P. McLean, A. Steinmetz, D. Fontana, C. Matthys, G. R. Warnick, M. Cheung, J. J. Albers and W. R. Hazzard, “Lipoprotein, Apolipoprotein and Lipolytic Enzyme Changes Following Estrogen Administration in Postmenoposal Women,” Lipid Research, Vol. 30, No. 2, 1989, p. 1895.
 M. Karbowink and R. J. Reiter, “Antioxidative Effect of Melatonin Inprotection against Cellular Damage Caused by Ionizing Radiation,” Proceedings of the Society for Experimental Biology and Medicine, Vol. 225, No. 1, 2000, pp. 9-22. doi:10.1046/j.1525-1373.2000.22502.x
 T. Chajek-Shaul, G. Friedman, O. Stein, E. Shiloni, J. Etienne and Y. Stein, “Mechanism of the Hypertriglyceridemia Induced by Tumor Necrosis Factor Administration to Rats,” Biochimica et Biophysica Acta, Vol. 1001, No. 30, 1989, pp. 316-324.
 N. R. Madamanchi and M. S. Runge, “Mitochondrial Dysfunction in Atherosclerosis,” Circulation Research, Vol. 100, No. 4, 2007, pp. 460-473.
 A. Onody, C. Csonka, Z. Giricz and P. Ferdinandy, “Hyperlipidemia Induced by a Cholesterol-Rich Diet Leads to Enhanced Peroxynitrite Formation in Rat Hearts,” Cardiovascular Research, Vol. 58, No. 3, 2003, pp. 663-670.
 V. Palani, R. K. Senthilkumaran and S .Govindasamy, “Biochemical Evaluation of Antitumor Effect of Muthu Marunthu (a Herbal Formulation) on Experimental Fibrosarcoma in Rats,” Journal of Ethnopharmacology, Vol. 65, No. 3, 1999, pp. 257-265.
 P. Jayamathi, V. Vishnupriya and S. K. Mohan, “Biochemical Effects of Plumbagin on Fibrosarcoma Induced Rats,” International Journal of Pharma Sciences and Research (IJPSR), Vol. 1, No. 8, 2010, pp. 320-325.
 B. Rajkapoor, M. Sankari, M. Sumithra, J. Anbu, N. Harikrishnan, M. Gobinath, V. Suba and R. Balaji, “Antitumor and Cytotoxic Effects of Phyllanthus polypyllus on Ehrlich Ascites Carcinoma and Human Cancer Cell Lines,” Bioscience, Biotechnology, and Biochemistry, Vol. 71, No. 9, 2007, pp. 2177-2183. doi:10.1271/bbb.70149
 H. C. Hogland, “Hematological Complications of Cancer Chemotherapy,” Seminar in Oncology, Vol. 9, No. 1, 1982, pp. 95-102.
 A. M. Abouelella, Y. E. Shahein, S. S. Tawfik and A. M. Zahran, “Phytotherapeutic Effects of Echinacea purpurea in Gamma-Irradiated Mice,” Journal of Veterinary Science, Vol. 8, No. 4, 2007, pp. 341-351.
 S. Mishima, K. Saito, H. Maruyama, M. Inoue, T. Yamashita, T. Ishida and Y. Gu, “Antioxidant and Immuno-Enhancing Effects of Echinacea purpurea,” Biological & Pharmaceutical Bulletin, Vol. 27, No. 7, 2004, pp. 1004-1009. doi:10.1248/bpb.27.1004