Background: Cardioxane has been probed in patients with advanced malignancies to protect the heart. Selenium, an essential micronutrient exerts varieties of functions such as antioxidant. The aim of this study was to test if cardioxane (CDX) and selenium (Se) have additive antioxidant protective effect on brain and heart, and their relation with dopamine levels. Methods: Thirty-six male Wistar rats divided in groups of 6 animals each, were treated as follows: G1, saline solution 0.9% (control); G2, 100 mg/kg of CDX; G3, 60 μg/kg of Se; G4, 20 mg/kg of 3-nitropropionic acid (3NP); G5, 3NP + CDX and G6, 3NP + Se. 3NP was used as an oxidative stress inducer. Drugs were administered intraperitoneally for 5 days. The animals were sacrificed on the last day of treatment and the brain and heart were extracted and used to measure lipid peroxidation, dopamine, glutathione (GSH), ATPase, calcium, and H2O2. Results: In G2 and G5, dopamine decreased in cortex and striatum while GSH increased in heart, cortex and cerebellum/medulla oblongata. ATPase activity increased in heart and cortex of groups 2, 3, 5 and 6. Lipoperoxidation and H2O2 increased in cortex of animals treated with 3NP. Conclusion: These results suggest that CDX increases antioxidant capacity in the brain and heart while selenium promotes alteration in dopamine metabolism in view of the capacity of 3NP to generate free radicals.
References
[1]
Rami, A., Ferger, D. and Krieglstein, J. (1997) Blockade of Calpain Proteolytic Activity Rescues Neurons from Glutamate Excitotoxicity. Neuroscience Research, 27, 93-97. https://doi.org/10.1016/S0168-0102(96)01123-6
[2]
Aliev, G., Obrenovich, M.E., Tabrez, S., et al. (2013) Link between Cancer and Alzheimer Disease via Oxidative Stress Induced by Nitric Oxide-Dependent Mitochondrial DNA Overproliferation and Deletion. Oxidative Medicine and Cellular Longevity, 2013, Article ID: 962984. https://doi.org/10.1155/2013/962984
[3]
Russo, E., Donato di Paola, E., Gareri, P., et al. (2013) Pharmacodynamic Potentiation of Antiepileptic Drugs’ Effects by Some HMG-CoA Reductase Inhibitors against Audiogenic Seizures in DBA/2 Mice. Pharmacological Research, 70, 1-12.
https://doi.org/10.1016/j.phrs.2012.12.002
[4]
Tetef, M.L., Synold, T.W., Chow, W., et al. (2001) Phase I Trial of 96-Hour Continuous Infusion of Cardioxane in Patients with Advanced Malignancies. Clinical Cancer Research, 7, 1569-1576.
[5]
Driver, A.S., Kodavanti, P.R. and Mundy, W.R. (2000) Age-Related Changes in Reactive Oxygen Species Production in Rat Brain Homogenates. Neurotoxicology and Teratology, 22, 175-181. https://doi.org/10.1016/S0892-0362(99)00069-0
[6]
Vogt, M.C. and Brüning, J.C. (2012) CNS Insulin Signaling in the Control of Energy Homeostasis and Glucose Metabolism from Embryo to Old Age. Trends in Endocrinology & Metabolism, 24, 76-84. https://doi.org/10.1016/j.tem.2012.11.004
[7]
Bellinger, F.P., Raman, A.V., Rueli, R.H., et al. (2012) Changes in Selenoprotein P in Substantia Nigra and Putamen in Parkinson’s Disease. Journal of Parkinson’s Disease, 2, 115-126.
[8]
Swapna, I., Sathya, K.V., Murthy, C.R. and Senthilkumaran, B. (2005) Membrane Alterations and Fluidity Changes in Cerebral Cortex during Ammonia Intoxication. NeuroToxicology, 335, 700-704.
[9]
Stefanello, F.M., Chiarani, F., Kurek, A.G., et al. (2005) Methionine alters Na+, K+ ATPase Activity, Lipid Peroxidation and Nonenzymatic Antioxidant Defenses in Rat Hippocampus. International Journal of Developmental Neuroscience, 23, 651-656. https://doi.org/10.1016/j.ijdevneu.2005.06.003
[10]
Calderon, G.D., Juarez, O.H., Hernandez, G.E., et al. (2013) Effect of an Antiviral and Vitamins A,C,D on Dopamine and Some Oxidative Stress Markers in Rat Brain Exposed to Ozone. Archives of Biological Sciences, 65, 1371-1379.
https://doi.org/10.2298/ABS1304371G
[11]
Junior, E.L., Leite, H.P. and Konstantyner, T. (2019) Selenium and Selenoproteins: From Endothelial Cytoprotection to Clinical Outcomes. Translational Research, 208, 85-104.
[12]
Reynolds, D.S., Carter, R.J. and Morton, A.J. (1998) Dopamine Modulates the Susceptibility of Striatal Neurons to 3-Nitropropionic Acid in the Rat Model of Huntington’s Disease. The Journal of Neuroscience, 18, 10116-10127.
https://doi.org/10.1523/JNEUROSCI.18-23-10116.1998
[13]
Calderón, G.D., Osnaya, B.N., García, A.R., et al. (2008) Levels of Glutathione and Some Biogenic Amines in the Human Brain Putamen after Traumatic Death. Proceedings of the Western Pharmacology Society, 51, 25-32.
[14]
Hissin, P.J. and Hilf, R. (1974) A Flurometric Method for Determination of Oxidized and Reduced Glutathione in Tissue. Analytical Biochemistry, 4, 214-226.
https://doi.org/10.1016/0003-2697(76)90326-2
[15]
Calderón-Guzmán, D., Espitia-Vázquez, I., López-Domínguez, A., et al. (2005) Effect of Toluene and Nutritional Status on Serotonin, Lipid Peroxidation Levels and Na+/K+-ATPase in Adult Rat Brain. Neurochemical Research, 30, 619-624.
https://doi.org/10.1007/s11064-005-2749-2
[16]
Fiske, C.H. and Subbarow, Y. (1925) The Colorimetric Determination of Phosphorus. The Journal of Biological Chemistry, 66, 375-400.
Gutteridge, J.M. and Halliwell, B. (1990) The Measurement and Mechanism of Lipid Peroxidation in Biological Systems. Trends in Biochemical Sciences, 15, 129-135.
https://doi.org/10.1016/0968-0004(90)90206-Q
[19]
Castilla-Serna, L. (2011) Practical Statistical Guide for Health Science. Editorial Trillas, México.
[20]
Smith, R.R., Dimayuga, E.R., Keller, J.N. and Maragos, W.F. (2005) Enhanced Toxicity to the Catecholamine Tyramine in Polyglutamine Transfected SH-SY5Y Cells. Neurochemical Research, 30, 527-531. https://doi.org/10.1007/s11064-005-2687-z
[21]
Browne, S.E. and Beal, M.F. (2006) Oxidative Damage in Huntington’s Disease Pathogenesis. Antioxidants & Redox Signaling, 8, 2061-2073.
https://doi.org/10.1089/ars.2006.8.2061
[22]
Qureshi, G.A., Qureshi, A.A., Memon, S.A. and Parvez, S.H. (2006) Impact of Selenium, Iron, Copper and Zinc in on/off Parkinson’s Patients on L-Dopa Therapy. Journal of Neural Transmission. Supplementa, 71, 229-236.
https://doi.org/10.1007/978-3-211-33328-0_24
[23]
Romero-Ramos, M., Venero, J.L., Cano, J. and Machado, A. (2000) Low Selenium Diet Induces Tyrosine Hydroxylase Enzyme in Nigrostriatal System of the Rat. Molecular Brain Research, 84, 7-16.
https://doi.org/10.1016/S0169-328X(00)00171-6
[24]
Castaño, A., Ayala, A., Rodriguez-Gomez, J.A., et al. (1995) Increase in Dopamine Turnover and Tyrosine Hydroxylase Enzyme in Hippocampus of Rats Fed on Low Selenium Diet. Journal of Neuroscience Research, 42, 684-691.
https://doi.org/10.1002/jnr.490420511
[25]
Mandavilli, B.S., Boldogh, I. and Van Houten, B. (2005) 3-Nitropropionic Acid-Induced Hydrogen Peroxide, Mitochondrial DNA Damage, and Cell Death Are Attenuated by Bcl-2 Overexpression in PC12 Cells. Molecular Brain Research, 133, 215-223. https://doi.org/10.1016/j.molbrainres.2004.10.033
[26]
Kumar, P., Kalonia, H. and Kumar, A. (2010) Protective Effect of Sesamol against 3-Nitropropionic Acid-Induced Cognitive Dysfunction and Altered Glutathione Redox Balance in Rats. Basic & Clinical Pharmacology & Toxicology, 107, 577-582.
https://doi.org/10.1111/j.1742-7843.2010.00537.x
[27]
Hoskins, B., Ho, I.K. and Meydrech, E.F. (1985) Effects of Aging and Morphine Administration on Calmodulin and Calmodulin-Regulated Enzymes in Striata of Mice. Journal of Neurochemistry, 44, 1069-1073.
https://doi.org/10.1111/j.1471-4159.1985.tb08726.x
[28]
Zheng, Y., Zhong, L. and Shen, X. (2005) Effect of Selenium-Supplement on the Calcium Signaling in Human Endothelial Cells. Journal of Cellular Physiology, 205, 97-106. https://doi.org/10.1002/jcp.20378
[29]
Barrett, C.W., Short, S.P. and Williams, C.S. (2016) Selenoproteins and Oxidative Stress-Induced Inflammatory Tumorigenesis in the Gut. Cellular and Molecular Life Sciences, 74, 607-616.
[30]
Naziroğlu, M., Kutluhan, S. and Yilmaz, M. (2008) Selenium and Topiramate Modulates Brain Microsomal Oxidative Stress Values, Ca2+-ATPase Activity, and EEG Records in Pentylentetrazol-Induced Seizures in Rats. Journal of Membrane Biology, 225, 39-49. https://doi.org/10.1007/s00232-008-9132-6
[31]
Hogg, N., Singh, R.J. and Kalyanaraman, B. (1996) The Role of Glutathione in the Transport and Catabolism of Nitric Oxide. FEBS Letters, 382, 223-228.
https://doi.org/10.1016/0014-5793(96)00086-5
