Comparative Assessment of Melatonin-Afforded Protection in Liver, Kidney and Heart of Male Mice against Doxorubicin Induced Toxicity — Oak Academic Publishing
Research ArticleOpen AccessGoogle Scholar indexed
Comparative Assessment of Melatonin-Afforded Protection in Liver, Kidney and Heart of Male Mice against Doxorubicin Induced Toxicity
Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Qassim, KSA.
1 Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Qassim, KSA.
Melatonin (MEL) was investigated for protection against the anthracycline antibiotic doxorubicin (Dox) that is well known for its oxidative damage to various body organs. It was aimed to have a comparison of this protection to heart, liver and kidney in the treated subjects. In this study, groups of mice were treated with Dox and melatonin and their individual or combined effects were evaluated by assessing lipidperoxidation, non-protein sulfhydryls (NP-SH) and nitrate/nitrite (NO) contents in these tissues. Plasma aminotransferases, LDH and CK-MB enzyme activities were measured. Moreover, these tissues were subject to histopathological assessment. MEL co-treatment significantly prevented any rise in lipidperoxides more significantly in heart and liver as compared to kidney. In tandem, MEL prevented a decline in GSH that was observed by Dox alone in liver and kidney. Dox significantly increased total NO levels in all the tissues. Melatonin at both dose levels could not afford protection against nitrosative stress. MEL in combination treatment provided significant (P < 0.01) decline in CK-MB at both the doses and only 5 mg/kg dose significantly prevented a rise in LDH activity and prevented any histopathological change. Melatonin, probably by behaving as an antioxidant prevented Dox-induced lipidperoxidation in heart, liver and kidney tissues and a decline in NP-SH. However, administration of MEL is able to decrease parameters of oxidative, and nitrosative stress in heart and liver more effectively than kidney.
R. H. Blum and S. K. Carter, “Adriamycin: A New Anticancer Drug with Significant Clinical Activity,” Annals of Internal Medicine, Vol. 80, No. 2, 1974, pp. 249-259. http://dx.doi.org/10.7326/0003-4819-80-2-249
P. K. Singal, C. M. R. Deally and L. E. Weinberg, “Subcellular Effects of Adriamycin in the Heart: A Concise Review,” Journal of Molecular and Cellular Cardiology, Vol. 19, No. 8, 1987, pp. 817-828. http://dx.doi.org/10.1016/S0022-2828(87)80392-9
M. P. O’Donnel, L. Pichels, B. L. Kasiske, L. Raij and W. F. Keane, “Adriamycin-Induced Chronic Proteinuria: A Structural and Functional Study,” Journal of Laboratory and Clinical Medicine, Vol. 106, No. 1, 1985, pp. 62-67.
T. Zima, V. Tesar, J. Crkovská, A. Stejskalová, J. Pláteník, J. Temínová, K. Nemecek, M. Janebová and S. Stípek, “ICRF-187 (Dexrazoxan) Protects from Adriamycin-Induced Nephrotic Syndrome in Rats,” Nephrology Dialysis Transplantation, Vol. 13, No. 8, 1998, pp. 1975-1979. http://dx.doi.org/10.1093/ndt/13.8.1975
S. Kotamraju, E. A. Konorev, J. Joseph and B. Kalyanaraman, “Doxorubicin-Induced Apoptosis in Endothelial Cells and Cardiomyocytes Is Ameliorated by Nitrone Spin Traps and Ebselen. Role of Reactive Oxygen and Nitrogen Species,” Journal of Biological Chemistry, Vol. 275, No. 43, 2000, pp. 33585-33592. http://dx.doi.org/10.1074/jbc.M003890200
G. Minotti, G. Cairo and E. Monti, “Role of Iron in Anthracycline Cardiotoxicity: New Tunes for an Old Song?” FASEB Journal, Vol. 13, No. 2, 1999, pp. 199-212.
J. H. Doroshow, G. Y. Looker, I. Ifrimand and C. E. Myers, “Prevention of Doxorubicin Cardiac Toxicity in the Mouse by Nacetylcysteine,” Journal of Clinical Investigation, Vol. 68, No. 4, 1981, pp. 1053-1064. http://dx.doi.org/10.1172/JCI110328
M. M. Al-Harbi, N. M. Al-Gharably, O. A. Al-Shabanah, A. M. Al-Bekairi, A. M. Osman and H. N. Tawfik, “Prevention of Doxorubicin-Induced Myocardial and Haematological Toxicities in Rats by the Iron Chelator Desferrioxamine,” Cancer Chemotherapy and Pharmacology, Vol. 31, No. 3, 1992, pp. 200-204. http://dx.doi.org/10.1007/BF00685548
P. K. Singal, N. Siveski-Iliskovic, M. Hill, T. Thomas and T. Li, “Combination Therapy with Probucol Prevents Adriamycin-Induced Cardiomyopathy,” Journal of Molecular and Cellular Cardiology, Vol. 27, No. 4, 1995, pp. 1055-1063. http://dx.doi.org/10.1016/0022-2828(95)90074-8
O. Bellini and E. Solcia, “Early and Late Sarcoplasmic Reticulum Changes in Doxorubicin Cardiomyopathy. An Ultrastructural Investigation with the Zinc Iodide-Osmium Tetroxide (ZIO) Technique,” Virchows Archiv B, Vol. 49, No. 1, 1985, pp. 137-152. http://dx.doi.org/10.1007/BF02912092
O. Al-Shabanah, M. Mansour, H. El-Kashef and A. AlBekair, “Captopril Ameliorates Myocardial and Hematological Toxicities Induced by Doxorubicin,” Biochemistry & Molecular Biology International, Vol. 45, No. 2, 1998, pp. 419-427.
O. A. Al-Shabanah, O. A. Badary, M. N. Nagi, N. AlGarably, A. Al-Rikabi and A. M. Al-Bekairi, “Thymoquinone Protects against Doxorubicin-Induced Cardiotoxicity without Compromising Its Antitumor Activity,” Journal of Experimental & Clinical Cancer Research, Vol. 17, No. 2, 1998, pp. 193-198.
M. N. Nagi and M. A. Mansour, “Protective Effect of Thymoquinone against Doxorubicin-Induced Cardiotoxicity in Rats: A Possible Mechanism of Protection,” Pharmacological Research, Vol. 41, No. 3, 2000, pp. 283-289. http://dx.doi.org/10.1006/phrs.1999.0585
P. K. Singal and G. N. Pierce, “Adriamycin Stimulates Low Affinity Calcium Binding and Lipid Peroxidation but Depresses Myocardial Function,” American Journal of Physiology, Vol. 1250, 1986, pp. 419-425.
C. E. Myers, W. P. McGuire, R. H. Liss, I. Ifirm, K. Grotzinger and R. C. Young, “Adriamycin: The Role of Lipid Peroxidation in Cardiac Toxicity and Tumor Response,” Science, Vol. 19, 1997, pp. 165-167.
I. Morishima, H. Matsui, H. Mukawa, K. Hayashi, Y. Toki, K. Okumura, T. Ito and T. Hayakawa, “Melatonin a Pineal Hormone with Antioxidant Property Protect against Adriamycin Cardiomyopathy in Rats,” Life Science, Vol. 63, No. 7, 2000, pp. 511-521. http://dx.doi.org/10.1016/S0024-3205(98)00302-6
N. Siveski-Iliskovic, N. Kaul and P. K. Singal, “Probucol Promotes Endogenous Antioxidants and Provides Protection against Adriamycin-Induced Cardiomyopathy in Rats,” Circulation, Vol. 89, 1994, pp. 2829-2835. http://dx.doi.org/10.1161/01.CIR.89.6.2829
M. F. Xu, P. L. Tang, Z. M. Qian and M. Ashraf, “Effects by Doxorubicin on the Myocardium Are Mediated by Oxygen Free Radicals,” Life Sciences, Vol. 68, No. 8, 2001, pp. 889-901. http://dx.doi.org/10.1016/S0024-3205(00)00990-5
J. H. Doroshow, “Effect of Anthracyclin Antibiotics on Oxygen Radical Formation in Rat Heart,” Cancer Research, Vol. 43, No. 2, 1983, pp. 460-472.
L. J. Ignarro, G. Cirino, A. Casini and C. Napoli, “Nitric Oxide as a Signaling Molecule in the Vascular System: An Overview,” Journal of Cardiovascular Pharmacology, Vol. 34, No. 6, 1999, pp. 879-886. http://dx.doi.org/10.1097/00005344-199912000-00016
V. W. T. Liu and P. L. Huang, “Cardiovascular Roles of Nitric Oxide: A Review of Insights from Nitric Oxide Synthase Gene Disrupted Mice,” Cardiovascular Research, Vol. 77, No. 1, 2008, pp. 19-29.
C. Napoli and L. J. Ignarro, “Nitric Oxide and Atherosclerosis,” Nitric Oxide, Vol. 5, No. 2, 2001, pp. 88-97. http://dx.doi.org/10.1006/niox.2001.0337
C. Napoli, F. de Nigris, S. Williams-Ignarro, O. Pignalosa, V. Sica and L. J. Ignarro, “Nitric Oxide and Atherosclerosis: An Update,” Nitric Oxide, Vol. 15, No. 4, 2006, pp. 265-279. http://dx.doi.org/10.1016/j.niox.2006.03.011
T. J. Rabelink and T. F. Luscher, “Endothelial Nitric Oxide Synthase: Host Defense Enzyme of the Endothelium?” Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 26, No. 2, 2006, pp. 267-271. http://dx.doi.org/10.1161/01.ATV.0000196554.85799.77
B. C. Kone, “Nitric Oxide Synthesis in the Kidney: Isoforms, Biosynthesis, and Functions in Health,” Seminars in Nephrology, Vol. 24, No. 4, 2004, pp. 299-315. http://dx.doi.org/10.1016/j.semnephrol.2004.04.002
J. W. Coddington, J. K. Hurst and S. V. Lymar, “Hydroxyl Radical Formation during Peroxynitrous Acid Decomposition,” Journal of the American Chemical Society, Vol. 121, No. 11, 1999, pp. 2438-2443. http://dx.doi.org/10.1021/ja982887t
M. L. Forsling, R. P. Stoughton, Y. Zhou, H. Kelestimur and C. Demaine, “The Role of the Pineal in the Control of the Daily Patterns of Neurohypophysial Hormone Secretion,” Journal of Pineal Research, Vol. 14, No. 1, 1993, pp. 45-51. http://dx.doi.org/10.1111/j.1600-079X.1993.tb00484.x
I. Kus, N. Akpolat, O. A. Ozen, A. Songur, A. Kavakli and M. Sarsilmaz, “Effects of Melatonin on Leydig Cells in Pinealectomized Rat: An Immunohistochemical Study,” Acta Histochemica, Vol. 104, No. 1, 2002, pp. 93-97. http://dx.doi.org/10.1078/0065-1281-00618
J. M. Guerrero and R. J. Reiter, “A Brief Survey of Pineal Gland-Immune System Interrelationships,” Endocrine Research, Vol. 18, No. 2, 1992, pp. 91-113. http://dx.doi.org/10.1080/07435809209035401
S. Cuzzocrea and R. J. Reiter, “Pharmacological Action of Melatonin in Shock, Inflammation and Ischemia/ Reperfusion Injury,” European Journal of Pharmacology, Vol. 426, No. 1-2, 2001, pp. 1-10. http://dx.doi.org/10.1016/S0014-2999(01)01175-X
L. Y. Zang, G. Cosma, H. Gardner and V. Vallyathan, “Scavenging of Reactive Oxygen Species by Melatonin,” Biochimica et Biophysica Acta, Vol. 1425, No. 3, 1998, pp. 469-477. http://dx.doi.org/10.1016/S0304-4165(98)00099-3
S. Kanno, A. Tomizawa, T. Hiura, Y. Osanai, M. Kakuta, Y. Kitajima, K. Koiwai, T. Ohtake, M. Ujibe and M. Ishikawa, “Melatonin Protects on Toxicity by Acetaminophen but Not on Pharmacological Effects in Mice,” Biological & Pharmaceutical Bulletin, Vol. 29, No. 3, 2006, pp. 472-476. http://dx.doi.org/10.1248/bpb.29.472
K. Suzuki, B. Murtuza, N. Suzuki, R. T. Smolenski and M. H. Yacoub, “Intracoronary Infusion of Skeletal Myoblasts Improves Cardiac Function in Doxorubicin-Induced Heart Failure,” Circulation, Vol. 104, No. 12, 2001, pp. I213-I217.
H. Ohkawa, N. Ohishi and K. Yagi, “Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction,” Analytical Biochemistry, Vol. 95, 1979, pp. 351-358. http://dx.doi.org/10.1016/0003-2697(79)90738-3
J. Sedlak and R. H. Lindsay, “Estimation of Total, Protein Bound and Non-Protein Sulfhydryl Groups in Tissue with Elman’s Reagent,” Analytical Biochemistry, Vol. 25, 1968, pp. 192-205. http://dx.doi.org/10.1016/0003-2697(68)90092-4
K. M. Miranda, M. G. Espey and D. A. Wink, “A Rapid, Simple Spectrophotometric Method for Simultaneous Detection of Nitrate and Nitrite,” Nitric Oxide: Biology and Chemistry, Vol. 5, No. 1, 2001, pp. 62-71.
M. M. Al-Harbi, S. Qureshi, M. Raza, M. M. Ahmed, A. B. Giangreco and A. H. Shah, “Influence of Anethole Treatment on the Tumour Induced by Ehrlich Ascites Carcinoma Cells in Paw of Swiss Albino Mice,” European Journal of Cancer Prevention, Vol. 4, No. 4, 1995, pp. 307-318. http://dx.doi.org/10.1097/00008469-199508000-00006
X. Liu, Z. Chen, C. C. Chua, Y. S. Ma, G. A. Youngberg, R. Hamdy and B. H. Chua, “Melatonin as an Effective Protector against Doxorubicin-Induced Cardiotoxicity,” American Journal of Physiology: Heart and Circulatory Physiology, Vol. 283, No. 1, 2002, pp. H254-H263.
E. Ozan, M. F. Sonmez, S. Ozan, N. Colakoglu, S. Yilmaz and T. Kuloglu, “Effects of Melatonin and Vitamin C on Cigarette Smoke-Induced Damage in the Kidney,” Toxicology and Industrial Health, Vol. 23, No. 8, 2007, pp. 479-485. http://dx.doi.org/10.1177/0748233708089023
A. I. Othman, M. A. El-Missiry, M. A. Amer and M. Arafa, “Melatonin Controls Oxidative Stress and Modulates Iron, Ferritin, and Transferrin Levels in Adriamycin Treated Rats,” Life Sciences, Vol. 83, No. 15-16, 2008, pp. 563-568. http://dx.doi.org/10.1016/j.lfs.2008.08.004
R. Hardeland, R. J. Reiter, B. Poeggeleer and D. X. Tan, “The Significance of the Metabolism of the Neurohormone Melatonin: Antioxidative Protection and Formation of Bioactive Substances,” Neuroscience & Biobehavioral Reviews, Vol. 17, No. 3, 1993, pp. 347-357. http://dx.doi.org/10.1016/S0149-7634(05)80016-8
R. J. Reiter, D. Melchiorri, E. Sewerynek, B. Poeggeler, L. Barlow-Walden, J. Chuang, G. G. Ortiz and D. AcunaCastroviejo, a Review of the Evidence Supporting Melatonin’s Role as an Antioxidant,” Journal of Pineal Research, Vol. 18, No. 1, 1995, pp. 1-11. http://dx.doi.org/10.1111/j.1600-079X.1995.tb00133.x
R. Schulz, M. V. Cohen, M. Behrends, J. M. Downey and G. Heusch, “Signal Transduction of Ischemic Preconditioning,” Cardiovascular Research, Vol. 52, No. 2, 2001, pp. 181-198. http://dx.doi.org/10.1016/S0008-6363(01)00384-4
C. Pieri, M. Marra, F. Moroni, R. Recchioni and F. Marcheselli, “Melatonin: A Peroxyl Radical Scavenger More Effective than Vitamin E,” Life Science, Vol. 55, No. 15, 1994, pp. pp. PL271-PL276.
Z. Chen, C. C. Chua, J. Gao, R. C. Hamdy and B. H. Chua, “Protective Effect of Melatonin on Myocardial Infarction,” American Journal of Physiology: Heart and Circulatory Physiology, Vol. 284, No. 5, 2003, pp. H1618-H1624.
T. Matsura, T. Nishida, A. Togawa, S. Horie, C. Kusumoto, S. Ohata, J. Nakada, Y. Ishibe, K. Yamada and Y. Ohta, “Mechanisms of Protection by Melatonin against Acetaminophen-Induced Liver Injury in Mice,” Journal of Pineal Research, Vol. 41, No. 3, 2006, pp. 211-219. http://dx.doi.org/10.1111/j.1600-079X.2006.00356.x
F. Oktem, F. Ozguner, H. Mollaoglu, A. Koyu and E. Uz, “Oxidative Damage in the Kidney Induced by 900-MHzEmitted Mobile Phone: Protection by Melatonin,” Archives of Medical Research, Vol. 36, No. 4, 2005, pp. 350-355. http://dx.doi.org/10.1016/j.arcmed.2005.03.021
E. Sahna, H. Parlakpinar, M. K. Ozer, F. Ozturk, F. Ozugurlu and A. Acet, “Melatonin Protects against Myocardial Doxorubicin Toxicity in Rats: Role of Physiological Concentrations,” Journal of Pineal Research, Vol. 35, No. 4, 2003, pp. 257-261. http://dx.doi.org/10.1034/j.1600-079X.2003.00084.x
E. Oz, D. Erbas, H. S. Sürücü and E. Düzgün, “Prevention of Doxorubicin-Induced Cardiotoxicity by Melatonin,” Molecular and Cellular Biochemistry, Vol. 282, No. 1-2, 2006, pp. 31-37. http://dx.doi.org/10.1007/s11010-006-1153-9
F. Raynaud, F. Mauviard, M. Geoffriau, B. Claustrat and P. Pevet, “Plasma 6-Hydroxymelatonin, 6-Sulfatoxymelatonin and Melatonin Kinetics after Melatonin Administration to Rats,” Biological Signals, Vol. 2, No. 6, 1993, pp. 358-366. http://dx.doi.org/10.1159/000109516