Share This Article:

Protective Effect of Curcumin on Anxiety, Learning Behavior, Neuromuscular Activities, Brain Neurotransmitters and Oxidative Stress Enzymes in Cadmium Intoxicated Mice

Full-Text HTML Download Download as PDF (Size:251KB) PP. 74-84
DOI: 10.4236/jbbs.2013.31008    3,756 Downloads   7,680 Views   Citations


Cadmium (Cd) exposure can induce acute lethal health-related threats to humans since it has an exceptional ability to accumulate in living organisms and cause toxicological effects. Curcumin (Cur) on the other hand has a wide variety of biological activities and several animal studies have suggested for a potential therapeutic or preventive effects against several ailments and infections. To study the effect of Cur on the toxicity of Cd, sixty Swiss-Webster strain male mice were divided into 6 groups of ten each at random. Group-1 served as the na?ve control and received no treatment. Group-2, 3 and 4 were the experimental controls and were administered once a day with a single oral dose of 50% dimethyl sulphoxide (DMSO), Cur (300 mg/kg) or Cd (100 mg/kg) respectively, for 2 weeks. Group-5 and 6 received Cur and Cd in combination once a day orally for 2 weeks except that Cur in a dose of 150 and 300 mg/kg to group 5 and 6 respectively, was administered one hour before Cd (100 mg/kg) administration to both groups. After treatment period, the animals were subjected to behavioral tests and thereafter, the animals were sacrificed for the estimation of neurotransmitters like serotonin (5-HT), dopamine (DA) and it’s metabolite 3,4-dihydroxyphenylacetic acid (DOPAC) as well as oxidative stress enzymes like lipid peroxides in the form of thiobarbituric acid–reactive substances (TBARS) and total glutathione (GSH) in the forebrain tissue. Cd reduced significantly the body weight gain, the locomotor activity, anxiety behavior in the plus maze and the learning capability (cognitive effect) in the shuttle-box test. Biochemical analysis further revealed that Cd exposure significantly altered the brain neurotransmitters and the oxidative stress enzymes. However, administration of Cur along with Cd had an ameliorating effect on all the behavioral and biochemical parameters studied herein and reduced the toxicity of Cd significantly and dose-dependently. Thus, Cur may be beneficial for anxiety, neuromuscular, and cognitive problems and protect from Cd intoxication.

Cite this paper

G. Abu-Taweel, J. Ajarem and M. Ahmad, "Protective Effect of Curcumin on Anxiety, Learning Behavior, Neuromuscular Activities, Brain Neurotransmitters and Oxidative Stress Enzymes in Cadmium Intoxicated Mice," Journal of Behavioral and Brain Science, Vol. 3 No. 1, 2013, pp. 74-84. doi: 10.4236/jbbs.2013.31008.


[1] IARC, “International Agency for Research on Cancer Monographs. Cadmium,” IARC Press, Lyon, 1993, pp. 119238.
[2] M. M. Brzoska and J. M. Jakoniuk, “Interactions between Cadmium and Zinc in the Organism,” Food and Chemical Toxicology, Vol. 39, No. 10, 2001, pp. 967-980. doi:10.1016/S0278-6915(01)00048-5
[3] M. M. Brzoska, K. Majewska and E. Kupraszewicz, “Effects of Low, Moderate and Relatively High Chronic Exposure to Cadmium on Long Bones Susceptibility to Fractures in Male Rats,” Environmental Toxicology and Pharmacology, Vol. 29, No. 3, 2010, pp. 235-245. doi:10.1016/j.etap.2010.01.005
[4] J. L. Li, R. Gao, S. Li, J. T. Wang, Z. X. Tang and S. W. Xu, “Testicular Toxicity Induced by Dietary Cadmium in Cocks and Ameliorative Effect by Selenium,” Biometals, Vol. 23, No. 4, 2010, pp. 695-705. doi:10.1007/s10534-010-9334-0
[5] P. B. Hammond and E. C. Foulkes, “Metal Ion Toxicity in Man and Animals,” In: H. Sigel, Ed., Metal Ions in Biological Systems, Marcel Dekker, New York, 1986, pp. 157-200.
[6] F. M. El-Demerdash, M. I. Yousef, F. S. Kedwany and H. H. Baghdadi, “Cadmium-Induced Changes in Lipid Peroxidation, Blood Hematology, Biochemical Parameters and Semen Quality of Male Rats: Protective Role of Vitamin E and Beta-Carotene,” Food and Chemical Toxicology, Vol. 42, No. 10, 2004, pp. 1563-1571. doi:10.1016/j.fct.2004.05.001
[7] P. F. de Souza, M. A. Diamante and H. Dolder, “Testis Response to Low Doses of Cadmium in Wistar Rats,” International Journal of Experimental Pathology, Vol. 91, No. 2, 2010, pp. 125-131. doi:10.1111/j.1365-2613.2009.00692.x
[8] M. Satoh, H. Koyama, T. Kaji, H. Kito and C. Tohyama, “Perspectives on Cadmium Toxicity Research,” Tohoku Journal of Experimental Medicine, Vol. 196, No. 1, 2002, pp. 23-32. doi:10.1620/tjem.196.23
[9] R. A. Goyer, J. Liu and M. P. Waalkes, “Cadmium and Cancer of Prostate and Testis,” Biometals, Vol. 17, No. 5, 2004, pp. 555-558. doi:10.1023/B:BIOM.0000045738.59708.20
[10] L. C. Xu, H. Sun, S. Y. Wang, L. Song, H. C. Chang and X. R. Wang, “The Roles of Metallothionein on CadmiumInduced Testes Damages in Sprague Dawley Rats,” Environmental Toxicology and Pharmacology, Vol. 20, No. 1, 2005, pp. 83-87. doi:10.1016/j.etap.2004.10.008
[11] S. Amara, H. Abdelmelek, C. Garrel, P. Guiraud, T. Douki, J. L. Ravanat, A. Favier, M. Sakly and K. Ben Rhouma, “Preventive Effect of Zinc against Cadmium-Induced Stress in the Rat Testis,” Journal of Reproductive Development, Vol. 54, No. 2, 2008, pp. 129-134. doi:10.1262/jrd.18110
[12] J. Thompson and J. Bannigan, “Cadmium: Toxic Effects on the Reproductive System and the Embryo,” Reproductive Toxicology, Vol. 25, No. 3, 2008, pp. 304-315. doi:10.1016/j.reprotox.2008.02.001
[13] B. I. Ognjanovic, S. D. Markovic, N. Z. Ethordevic, I. S. Trbojevic, A. S. Stajn and Z. S. Saicic, “Cadmium-Induced Lipid Peroxidation and Changes in Antioxidant Defense System in the Rat Testes: Protective Role of Coenzyme Q(10) and Vitamin E,” Reproductive Toxicology, Vol. 29, No. 2, 2010, pp. 191-197. doi:10.1016/j.reprotox.2009.11.009
[14] S. Jimi, M. Uchiyama, A. Takaki, J. Suzumiya and S. Hara, “Mechanisms of Cell Death Induced by Cadmium and Arsenic,” Annals of New York Academy of Sciences, Vol. 1011, No. 1, 2004, pp. 325-331. doi:10.1196/annals.1293.032
[15] R. Sen Gupta, J. Kim, C. Gomes, S. Oh, J. Park, W. B. Im, J. Y. Seong, R. S. Ahn, H. B. Kwon and J. Soh, “Effect of Ascorbic Acid Supplementation on Testicular Steroidogenesis and Germ Cell Death in Cadmium-Treated Male Rats,” Molecular and Cellular Endocrinology, Vol. 221, No. 1-2, 2004, pp. 57-66. doi:10.1016/j.mce.2004.03.012
[16] M. P. Waalkes, T. P. Coogan and R. A. Barter, “Toxicological Principles of Metal Carcinogenesis with Special Emphasis on Cadmium,” Critical Review of Toxicology, Vol. 22, No. 3-4, 1992, pp. 175-201. doi:10.3109/10408449209145323
[17] M. P. Waalkes, “Cadmium Carcinogenesis in Review,” Journal of Inorganic Biochemistry, Vol. 79, No. 1, 2000, pp. 241-244. doi:10.1016/S0162-0134(00)00009-X
[18] National Toxicology Program, “NTP Toxicology and Carcinogenesis in Studies of Turmeric Oleoresin (CAS No. 8024-37-1) (Major Component 79% 85% Curcumin, CAS No. 458-37-7) in F344/N Rats and B6C3F1 Mice (Feed Studies),” National Toxicology Program Technical Reproductive Services, Vol. 427, 1993, pp. 1-275.
[19] I. Rahman, S. K. Biswas and P. A. Kirkham, “Regulation of Inflammation and Redox Signaling by Dietary Polyphenols,” Biochemical Pharmacology, Vol. 72, No. 11, 2006, pp. 1439-1452. doi:10.1016/j.bcp.2006.07.004
[20] N. Tirkey, G. Kaur, G. Vij and K. Chopra, “Curcumin, a Diferuloylmethane, Attenuates Cyclosporine-Induced Renal Dysfunction and Oxidative Stress in Rat Kidneys,” BMC Pharmacology, Vol. 5, 2005, pp. 1-15. doi:10.1186/1471-2210-5-15
[21] N. Khanna, “Turmeric: Nature’s Precious Gift,” Current Science, Vol. 76, No. 10, 1999, pp. 1351-1356. doi:10.1007/s10495-006-6715-5
[22] J. Chen, X. Q. Tang, J. L. Zhi, Y. Cui, H. M. Yu, E. H. Tang, S. N. Sun, J. Q. Feng and P. X. Chen, “Curcumin Protects PC12 Cells against 1-Methyl-4-phenylpyridinium Ion-Induced Apoptosis by bcl-2-Mitochondria-ROS-iNOS Pathway,” Apoptosis, Vol. 11, No. 6, 2006, pp. 943-953.
[23] L. Perez-Arriaga, M. L. Mendoza-Magana, R. Cortes-Zarate, A. Corona-Rivera, L. Bobadilla-Morales, R. TroyoSanroman and M. A. Ramirez-Herrera, “Cytotoxic Effect of Curcumin on Giardia Lamblia Trophozoites,” Acta Tropica, Vol. 98, No. 2, 2006, pp. 152-161.
[24] R. S. Ramsewak, D. L. DeWitt and M. G. Nair, “Cytotoxicity, Antioxidant and Anti-Inflammatory Activities of Curcumins IIII from Curcuma Longa,” Phytomedicine, Vol. 7, No. 4, 2000, pp. 303-308. doi:10.1016/S0944-7113(00)80048-3
[25] B. B. Aggarwal, C. Sundaram, N. Malani and H. Ichikawa, “Curcumin: The Indian Solid Gold,” Advances in Experimental Medical Biology, Vol. 595, 2007, pp. 1-75. doi:10.1007/978-0-387-46401-5_1
[26] O. Ciftci, S. Tanyildizi and A. Godekmerdan, “Protective Effect of Curcumin on Immune System and Body Weight Gain on Rats Intoxicated with 2,3,7,8-Tetrachlorodibenzop-dioxin (TCDD),” Immunopharmacology and Immunotoxicology, Vol. 32, No. 1, 2010, pp. 99-104. doi:10.3109/08923970903164318
[27] G. M. Cole, B. Teter and S. A. Frautschy, “Neuroprotective Effects of Curcumin,” Advances in Experimental Medicine and Biology, Vol. 595, 2007, pp. 197-212. doi:10.1007/978-0-387-46401-5_8
[28] A. Kuhad, S. Pilkhwal, S. Sharma, N. Tirkey and K. Chopra, “Effect of Curcumin on Inflammation and Oxidative Stress in Displatin-Induced Experimental Nephrotoxicity,” Journal of Agricultural and Food Chemistry, Vol. 55, No. 25, 2007, pp. 10150-10155. doi:10.1021/jf0723965
[29] O. Ciftci, I. Ozdemir, S. Tanyildizi, S. Yildiz and H. Oguzturk, “Antioxidative Effects of Curcumin, β-Myrcene and 1,8-Cineole against 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Oxidative Stress in Rats Liver,” Toxicology and Industrial Health, Vol. 27, No. 5, 2011, pp. 447-453. doi:10.1177/0748233710388452
[30] O. Ciftci, A. Beytur, O. Cakir, N. Gurbuz and N. Vardi, “Comparison of Reproductive Toxicity Caused by Cisplatin and Novel Platinum-N-Heterocyclic Carbine Complex in Male Rats,” Basic and Clinical Pharmacology and Toxicology, Vol. 109, No. 5, 2011, pp. 328-333. doi:10.1111/j.1742-7843.2011.00737.x
[31] O. Ciftci, M. Aydin, I. Ozdemir and N. Vardi, “Quercetin Prevents 2,3,7,8-Tetrachlorodibenzo-p-dioxin-Induced Testicular Damage in Rats,” Andrologia, Vol. 44, No. 3, 2012, pp. 164-173. doi:10.1111/j.1439-0272.2010.01126.x
[32] O. Ciftci, I. Ozdemir, M. Aydin and A. Beytur, “Beneficial Effects of Chrysin on the Reproductive System of Adult Male Rats,” Andrologia, Vol. 44, No. 3, 2012, pp. 181-186. doi:10.1111/j.1439-0272.2010.01127.x
[33] H. Ahsan, N. Parveen, N. U. Khan and S. M. Hadi, “ProOxidant, Anti-Oxidant and Cleavage Activities on DNA of Curcumin and Its Derivatives Demethoxycurcumin and Bisdemethoxycurcumin,” Chemical and Biological Interaction, Vol. 121, No. 2, 1999, pp. 161-175. doi:10.1016/S0009-2797(99)00096-4
[34] G. K. Jayaprakasha, L. J. Rao and K. K. Sakariah, “Antioxidant Activities of Curcumin, Demethoxycurcumin and Bisdemethoxycurcumin,” Food Chemistry, Vol. 98, No. 4, 2006, pp. 720-724. doi:10.1016/j.foodchem.2005.06.037
[35] P. M. Wall and G. Messier, “Methodological and Conceptual Issues in the Use of Elevated Plus-Maze as a Psychological Measurement Instrument of Animal AnxietyLike Behavior,” Neuroscience and Biobehavior Review, Vol. 25, No. 3, 2001, pp. 275-286. doi:10.1016/S0149-7634(01)00013-6
[36] O. E. Patrick, M. Hirohisa, K. Masahira and M. Koreaki, “Central Nervous System Bioaminergic Responses to Mechanic Trauma,” Surgical Neurology, Vol. 35, No. 4, 1991, pp. 273-279. doi:10.1016/0090-3019(91)90004-S
[37] H. Ohkawa, N. Ohishi and K. Tgi, “Assay for Lipid Peroxides in Animal Tissues by Thiobarbituric Acid Reaction,” Annals of Chemistry, Vol. 95, No. 2, 1979, pp. 351358.
[38] M. J. Mangino, M. K. Murphy and G. G. Glabar, “Protective Effects of Glycine during Hypothermic Renal Ischemic Reperfusion Injury,” American Journal of Physiology, Vol. 261, No. 5, 1991, pp. F841-F848.
[39] T. L. Sorell and J. H. Graziano, “Effect of Oral Cadmium Exposure during Pregnancy on Maternal and Fetal Zinc Metabolism in the Rat,” Toxicology and Applied Pharmacology, Vol. 102, No. 3, 1990, pp. 537-545. doi:10.1016/0041-008X(90)90048-Y
[40] C. Claverie, R. Corbella, D. Martin and C. Diaz, “Protective Effects of Zinc on Cadmium Toxicity in Rodents,” Biological Trace Element Research, Vol. 75, No. 1-3, 2000, pp. 1-9. doi:10.1385/BTER:75:1-3:1
[41] B. Baranski, “Effect of Exposure of Pregnant Rats to Admium on Prenatal and Postnatal Development of the Young,” Journal of Hygiene, Epidemiology and Microbiology, Vol. 29, No. 3, 1984, pp. 253-262.
[42] I. Desi, L. Nagymajtenyi and H. Schulz, “Behavioural and Neurotoxicological Changes Caused by Cadmium Treatment of Rats during Development,” Journal of Applied Toxicology, Vol. 18, No. 1, 1998, pp. 63-70. doi:10.1002/(SICI)1099-1263(199801/02)18:1<63::AID-JAT475>3.0.CO;2-Z
[43] G. Liu and J. Elsner, “Review of the Multiple Chemical Exposure Factors Which May Disturb Human Behavioral Development,” Sozial-und Praventivmedizin, Vol. 40, 1995, pp. 209-217. doi:10.1007/BF01354475
[44] L. Nagymajtenyi, H. Schulz and I. Desi, “Behavioural and Functional Neurotoxicological Change Caused by Cadmium in a Three-Generational Study in Rats,” Human and Experimental Toxicology, Vol. 16, No. 12, 1997, pp. 691-699. doi:10.1177/096032719701601201
[45] K. Lehotzky, G. Ungvary, D. Polinak and A. Kiss, “Behavioral Deficits Due to Prenatal Exposure to Cadmium Chloride in CFY Rat Pups,” Neurotoxicology and Teratology, Vol. 12, No. 2, 1990, pp. 169-172. doi:10.1016/0892-0362(90)90130-5
[46] S. Morita, “Defense Mechanisms against Cadmium Toxicity I. A Biochemical and Histological Study of the Effects of Pretratment with Cadmium on the Acute Oral Toxicity of Cadmium in Mice,” Japanese Journal of Pharmacology, Vol. 35, 1984, pp. 129-141. doi:10.1254/jjp.35.129
[47] M. Devi, D. A. Thomas, J. T. Barber and M. A. Fingerman, “Accumulation and Physiological and Biochemical Effects of Cadmium in a Simple Aquatic Food Chain,” Ecotoxicology and Environmental Saftey, Vol. 33, No. 1, 1996, pp. 38-43. doi:10.1006/eesa.1996.0004
[48] B. Ognjanovic, R. V. Zikic, A. Stajn, Z. S. Saicic, M. M. Kostic and V. M. Petrovic, “The Effects of Selenium on the Antioxidant Defense System in the Liver of Rats Exposed to Cadmium,” Physiological Research, Vol. 44, No. 5, 1995, pp. 293-300.
[49] E. Casalino, C. Sblano and C. Landriscina, “Enzyme Activity Alteration by Cadmium Administration to Rats: The Possibility of Iron Involvement in Lipid Peroxidation,” Archives of Biochemistry and Biophysics, Vol. 346, No. 2, 1997, pp. 171-179. doi:10.1006/abbi.1997.0197
[50] A. Stajn, R. V. Zikic, B. Ognjanovic, Z. S. Saicic, S. Z. Pavlovic, M. M. Kostic and V. M. Petrovic, “Effect of Cadmium and Selenium on the Antioxidant Defense System in Rat Kidneys,” Comparative Biochemistry and Physiology, Vol. 117C, No. 2, 1997, pp. 167-172.
[51] M. M. Kostic, B. Ognjanovic, S. Dimitrijevic, R. V. Zikic, A. Stajn and G. L. Rosic, “Cadmium-Induced Changes of Antioxidant and Metabolic Status in Red Blood Cells of Rats: In Vivo Effects,” European Journal of Haematology, Vol. 51, No. 2, 1993, pp. 86-92. doi:10.1111/j.1600-0609.1993.tb01598.x
[52] R. V. Zikic, A. S. Stajn, B. I. Ognjanovic, Z. S, Saicic, M. M. Kostic, S. Z. Pavloviv and V. M. Petrovic, “The Effect of Cadmium and Selenium on the Antioxidant Enzyme Activities in Rat Heart,” Journal of Environmental Pathology, Toxicology and Oncology, Vol. 17, No. 3-4, 1998, pp. 259-264.
[53] S. Z. Pavlovic, B. I. Ognjanovic, A. S. Stajn, R. V. Zikic, Z. S. Saicic and V. M. Petrovic, “Antioxidant Defense System in Skeletal Muscle of Rats Treated with Cadmium. A Possible Protective Role of Coenzyme Q10,” Jugoslavia Medical Biochemistry, Vol. 20, No. 4, 2001, pp. 229-235.
[54] E. Casalino, C. Sblano and C. Landriscina, “Enzyme Activity Alteration by Cadmium Administration to Rats: The Possibility of Iron Involvement in Lipid Peroxidation,” Archives of Biochemistry and Biophysics, Vol. 346, No. 2, 1997, pp. 171-179. doi:10.1006/abbi.1997.0197
[55] J. G. Wilson, “Mechansims of Teratogenesis,” American Journal of Psychiatry, Vol. 136, 1973, pp. 129-132.
[56] R. M. Freitas, S. M. M. Vasconcelos, F. C. F. Souza, G. S. B. Viana and M. M. F. Fonteles, “Monoamine Levels after Pilocarpine-Induced Status Epilepticus in Hippocampus and Frontal Cortex of Wistar Rats,” Neuroscience Letters, Vol. 370, No. 2-3, 2004, pp. 196-200. doi:10.1016/j.neulet.2004.08.024
[57] V. S. Nascimento, A. A. Oliveira, R. M. Freitas, F. C. Sousa, S. M. M. Vasconcelos, G. S. B. Viana and M. M. F. Fonteles, “Pilocarpine-Induced Status Epilepticus: Monoamine Level, Muscarinic and Dopaminergic Receptors Alterations in Striatum of Young Rats,” Neuroscience Letters, Vol. 383, No. 1-2, 2005, pp. 165-170. doi:10.1016/j.neulet.2005.04.006
[58] V. D. Petkov, S, Belcheva, E. Konstantinova and R. Kehayov, “Participation of Different 5-HT Receptors in the Memory Process in Rats and Its Modulation by the Serotonin Depletor p-Chlorophenylalanine,” Acta Neurobiologiae Experimentalis (Wars), Vol. 55, 1995, pp. 243252.
[59] G. M. Abu-Taweel, J. S. Ajarem and M. Ahmad, “Neurobehavioral Toxic Effects of Perinatal Oral Exposure to Aluminum on the Developmental Motor Reflexes, Learning, Memory and Brain Neurotransmitters of Mice Offspring,” Pharmacology Biochemistry and Behavior, Vol. 101, No. 1, 2012, pp. 49-56. doi:10.1016/j.pbb.2011.11.003
[60] G. Richter-Levin and M. Segal, “The Effects of Serotonin Depletion and Raphe Grafts on Hippocampal Electrophysiology and Behavior,” The Journal of Neuroscience, Vol. 11, No. 6, 1991, pp. 1585-1596.
[61] I. S. Jamall and J. J. Sprowls, “Effects of Cadmium and Dietary Selenium on Cytoplasmic and Mitochondrial Antioxidant Defense Systems in the Heart of Rats Fed High Dietary Copper,” Toxicology and Applied Pharmacology, Vol. 87, No. 1, 1987, pp. 102-110. doi:10.1016/0041-008X(87)90088-3
[62] S. Sarkar, P. Yadav and D. Bhatnagar, “Lipid Peroxidative Damage on Cadmium Exposure and Alterations in Antioxidant System in Rat Erythrocytes: A Study with Relation to Time,” Biometals, Vol. 11, No. 2, 1998, pp. 153-157. doi:10.1023/A:1009286130324
[63] E. Casalino, G. Valzaretti, C. Sblano, V. Landriscina, M. Felice Tesse and C. Landriscina, “Antioxidant Effect of Hydroxytyrosol (DPE) and Mn2+ in Liver of CadmiumIntoxicated Rats,” Comparative Biochemistry and Physiology, Vol. C133, No. 4, 2002, pp. 625-632.
[64] B. Ognjanovic, S. Z. Pavlovic, S. D. Maletic, R. V. ?ikic, A. ?tajn, R. M. Radojicic, Z. S. Saicic and V. M. Petrovic, “Protective Influence of Vitamin E on Antioxidant Defense System in the Blood of Rats Treated with Cadmium,” Physiological Research, Vol. 52, No. 5, 2003, pp. 563-570.
[65] Z. A. Shaikh, T. T. Vu and K. Zaman, “Oxidative Stress as a Mechanism of Chronic Cadmium-Induced Hepatotoxicity and Renal Toxicity and Protection by Antioxidants,” Toxicology and Applied Pharmacology, Vol. 154, No. 3, 1999, pp. 256-263. doi:10.1006/taap.1998.8586
[66] M. Waisberg, P. Joseph, B. Hale and D. Beyersmann, “Molecular and Cellular Mechanisms of Cadmium Carcinogenesis: A Review,” Toxicology, Vol. 192, No. 2-3, 2003, pp. 95-117. doi:10.1016/S0300-483X(03)00305-6
[67] S. J. Stohs, D. Bagchi, E. Hassoun and M. Bagchi, “Oxidative Mechanisms in the Toxicity of Chromium and Cadmium Ions,” Journal of Environmental Pathology, Toxicology and Oncology, Vol. 20, No. 2, 2001, pp. 77-88. doi:10.1615/JEnvironPatholToxicolOncol.v20.i2.10
[68] V. Calabrese, D. A. Butterfield and A. M. Stella, “Nutritional Antioxidants and the Heme Oxygenase Pathway of Stress Tolerance: Novel Targets for Neuroprotection in Alzheimer’s Disease,” Italian Journal of Biochemistry, Vol. 52, No. 4, 2003, pp. 177-181.
[69] K. Kitani, T. Yokozawa and T. Osawa, “Interventions in Aging and Age-Associated Pathologies by Means of Nutritional Approaches,” Annals of New York Academy of Sciences, Vol. 1019, No. 1, 2004, pp. 424-426. doi:10.1196/annals.1297.075
[70] R. Motterlini, R. Foresti, R. Bassi and C. J. Green, “Curcumin, an Antioxidant and Anti-Inflammatory Agent, Induces Heme Oxygenase-1 and Protects Endothelial Cells against Oxidative Stress,” Free Radical Biology and Medicine, Vol. 28, 2000, pp. 1303-1312. doi:10.1016/S0891-5849(00)00294-X
[71] A. Ray, “Cancer Preventive Role of Selected Dietary Factors,” Indian Journal of Cancer, Vol. 42, No. 1, 2005, pp. 11-20. doi:10.4103/0019-509X.15095
[72] A. I. Ghoneim, A. B. Abdel-Naim, A. E. Khalifa and E. S. El-Denshary, “Protective Effects of Curcumin against Ischaemia/Reperfusion Insult in Rat Forebrain,” Pharmacological Research, Vol. 46, No. 3, 2002, pp. 273-279. doi:10.1016/S1043-6618(02)00123-8
[73] M. Thiyagarajan and S. S. Sharma, “Neuroprotective Effect of Curcumin in Middle Cerebral Artery Occlusion Induced Focal Cerebral Ischemia in Rats,” Life Sciences, Vol. 74, No. 8, 2004, pp. 969-985. doi:10.1016/j.lfs.2003.06.042
[74] V. Rajakrishnan, P. Viswanathan, K. N. Rajasekharan and V. P. Menon, “Neuroprotective Role of Curcumin from Curcuma Longa on Ethanolinduced Brain Damage,” Phytotherapy Research, Vol. 13, No. 7, 1999, pp. 571-574. doi:10.1002/(SICI)1099-1573(199911)13:7<571::AID-PTR494>3.0.CO;2-7
[75] G. P. Lim, T. Chu, F. Yang, W. Beech, S. A. Frautschy and G. M. Cole, “The Curry Spice Curcumin Reduces Oxidative Damage and Amyloid Pathology in an Alzheimer Transgenic Mouse,” Journal of Neuroscience, Vol. 21, No. 21, 2001, pp. 8370-8377.
[76] S. J. Stohs and D. Bagchi, “Oxidative Mechanisms in the Toxicity of Metal Ions,” Free Radical Biology and Medicine, Vol. 18, No. 2, 1995, pp. 321-336. doi:10.1016/0891-5849(94)00159-H
[77] R. Anane and E. E. Creppy, “Lipid Peroxidation as Pathway of Aluminium Cytotoxicity in Human Skin Fibroblast Cultures: Prevention by Superoxide Dismutase and Catalase and Vitamins E and C,” Human Experimental Toxicology, Vol. 20, No. 9, 2001, pp. 477-481. doi:10.1191/096032701682693053
[78] P. O’brien and H. J. Salasinski, “Evidence That the Reactions of Cadmium in the Presence of Metallothionein Can Produce Hydroxyl Radicals,” Archives of Toxicology, Vol. 72, No. 11, 1998, pp. 690-700. doi:10.1007/s002040050562
[79] T. Koizumi, G. Shirakura, H. Kumagai, H. Tatsumoto and K. T. Suzuki, “Mechanism of Cadmium-Induced Cytotoxicity in Rat Hepatocytes: Cadmium-Induced Active Oxygen-Related Permeability Changes of the Plasma Membrane,” Toxicology, Vol. 114, 1996, pp. 124-134. doi:10.1016/S0300-483X(96)03477-4
[80] S. K. Tandon, S. Singh, S. Prasad, K. Khandekar, V. K. Dwivedi, M. Chatterjee and N. Mathur, “Reversal of Cadmium Induced Oxidative Stress by Chelating Agent, Antioxidant or Their Combination in Rat,” Toxicology Letters, Vol. 145, No. 3, 2003, pp. 211-217. doi:10.1016/S0378-4274(03)00265-0
[81] B. Ognjanovic, S. D. Markovic, S. Z. Pavlovic, R. V. ?ikic, A. ?tajn and Z. S. Saicic, “Combined Effects of Coenzyme Q10 and Vitamin E in Cadmium Induced Alterations of Antioxidant Defense System in the Rat Heart,” Environmental Toxicology and Pharmacology, Vol. 22, 2006, pp. 219-224. doi:10.1016/j.etap.2006.03.008
[82] B. Halliwell and J. M. C. Gutteridge, “Free Radicals in Biology and Medicine,” 3rd Edition, Oxford University Press, New York, 1999.
[83] M. Mates, “Effects of Antioxidant Enzymes in the Molecular Control of Reactive Oxygen Species Toxicology,” Toxicology, Vol. 153, No. 1, 2000, pp. 83-104. doi:10.1016/S0300-483X(00)00306-1
[84] O. W. Griffith, “Biological and Pharmacologic Regulation of Mammalian Glutathione Synthesis,” Free Radical Biology and Medicine, Vol. 27, No. 9-10, 1999, pp. 922935. doi:10.1016/S0891-5849(99)00176-8
[85] R. E. Beyer, “The Role of Ascorbate in Antioxidant Protection of Biomolecules: Interaction with Vitamin E and Coenzyme Q,” Journal of Bioenergy and Biomembrane, Vol. 26, No. 4, 1994, pp. 349-358. doi:10.1007/BF00762775

comments powered by Disqus

Copyright © 2017 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.