All Title Author
Keywords Abstract

Effect of Chronic Administration of Cadmium on Anxiety-Like, Depression-Like and Memory Deficits in Male and Female Rats: Possible Involvement of Oxidative Stress Mechanism

DOI: 10.4236/jbbs.2018.85016, PP. 240-268

Keywords: Cadmium, Depression-Like, Anxiety-Like, Memory, Oxidative Stress

Full-Text   Cite this paper   Add to My Lib


The main objective of this work is to study the effect of chronic administration of cadmium (Cd) on the level of depression-like, anxiety-like, memory state and oxidative stress in male and female Wistar rats. For this purpose, this study was conducted with 24 rats for each gender. Four groups were constituted: (Group 1: Control): received saline solution NaCl (0.9%), (Group 2: Cd-0.25; Group 3: Cd-0.5; Group 4: Cd-1): received daily 0.25 mg/kg, 0.5 mg/kg and 1 mg/kg of Cd respectively during 8 weeks. After treatment period, animals were tested in the open-field, elevated plus maze tests for anxiety-like behavior, and forced swimming test for depression-like behavior. The Y maze was used to evaluate the working memory and the Morris Water Maze, to evaluate space learning and spatial memory. The results revealed that in males, all doses of Cd provoke depression-like, while in females only the group treated with 1 mg/kg Cd shows elevated depression-like behavior. In regard to anxiety-like behavior, Cd induces an anxiogenic effect in both genders tests. In the Y-Maze test, both males and females expressed a low percentage of alternations, suggesting that working memory was affected by Cd at 1 mg/kg. In the Morris Water Maze test, the space learning and spatial memory were significantly impaired in the group Cd-1. Neurochemical analysis showed that levels of nitric oxide and lipid peroxidation in the hippocampus were significantly increased after Cd treatments. Overall analysis of our data revealed that Cd caused significant alterations in the examined parameters that were sex-dependent and dose-dependent.


[1]  Goyer, R.A. and Clarkson, T.W. (1996) Toxic Effects of Metals. In Amdur, M.O., Doull, J.D. and Klaassen, C.D., Eds., Casarett and Doull’s Toxicology, 4th Edition, Pergamon Press, New York, 623-680.
[2]  Mortada, W.I., Sobh, M.A., El-Defrawy, M.M. and Farahat, S.E. (2002) Reference Intervals of Cadmium, Lead, and Mercury in Blood, Urine, Hair, and Nails among Residents in Mansoura City, Nile Delta, Egypt. Environmental Research, 90, 104-110.
[3]  Jones, M.M. and Cherian, M.G. (1990) The Search for Chelate Antagonists for Chronic Cadmium Intoxication. Toxicology, 62, 1-25.
[4]  Zadorozhnaja, T.D., Little, R.E., Miller, R.K., Mendel, N.A., Taylor, R.J., Presley, B.J. and Gladen, B.C. (2013) Concentrations of Arsenic, Cadmium, Copper, Lead, Mercury, and Zinc in Human Placentas from Two Cities in Ukraine. Journal of Toxicology and Environmental Health, 61, 255-263.
[5]  Shukla, A., Shukla, G.S. and Srimal, R. (1996) Cadmium-Induced Alterations in Blood-Brain Barrier Permeability and Its Possible Correlation with Decreased Microvessel Antioxidant Potential in Rat. Human & Experimental Toxicology, 15, 400-405.
[6]  Pihl, R.O. and Parkes, M. (1977) Hair Element Content in Learning Disabled Children. Science, 198, 204-206.
[7]  Cao, Y., Chen, A., Radcliffe, J., Dietrich, K.N., Jones, R.L., Caldwell, K. and Rogan, W.J. (2009) Postnatal Cadmium Exposure, Neurodevelopment, and Blood Pressure in Children at 2, 5, and 7 Years of Age. Environmental Health Perspectives, 117, 1580-1586.
[8]  Okuda, B., Iwamoto, Y., Tachibana, H. and Sugita, M. (1997) Parkinsonism after Acute Cadmium Poisoning. Clinical Neurology and Neurosurgery, 99, 263-265.
[9]  Dési, I., Nagymajtényi, L. and Schulz, H. (1998) Behavioural and Neurotoxicological Changes Caused by Cadmium Treatment of Rats during Development. Journal of Applied Toxicology, 18, 63-70.<63::AID-JAT475>3.0.CO;2-Z
[10]  Stoltenburg-Didinger, G. (1994) Neuropathology of the Hippocampus and Its Susceptibility to Neurotoxic Insult. Neurotoxicology, 15, 445-450.
[11]  Altmann, L., Sveinsson, K. and Wiegand, H. (1991) Long-Term Potentiation in Rat Hippocampal Slices Is Impaired Following Acute Lead Perfusion. Neuroscience Letters, 128, 109-112.
[12]  Brenneman, K., Wong, B., Buccellato, M., Costa, E.R., Gross, E. and Dorman, D.C. (2000) Direct Olfactory Transport of Inhaled Manganese ((54)MnCl(2)) to the Rat Brain: Toxicokinetic Investi-gations in a Unilateral Nasal Occlusion Model. Toxicology and Applied Pharmacology, 169, 238-248.
[13]  De Souza Predes, F., Diamante, M.A.S. and Dolder, H. (2010) Testis Response to Low Doses of Cadmium in Wistar Rats. International Journal of Experimental Pathology, 91, 125-131.
[14]  Lafuente, A., Marquez, N., Pazo, D. and Esquifino, A.I. (2001) Cadmium Effects on Dopamine Turnover and Plasma Levels of Prolactin, GH and ACTH. Journal of Physiology and Biochemistry, 57, 231-236.
[15]  Wu, X., Guo, X., Wang, H., Zhou, S., Li, L., Chen, X., Wang, G., Liu, J., Ge, H.-S. and Ge, R.-S. (2017) A Brief Exposure to Cadmium Impairs Leydig Cell Regeneration in the Adult Rat Testis. Scientific Reports, 7, Article No. 6337.
[16]  Wang, L.-S., Wang, L., Wang, L., Wang, G., Li, Z.-H. and Wang, J.-J. (2009) Effect of 1-Butyl-3-methylimidazolium Tetrafluoroborate on the Wheat (Triticum aestivum L.) Seedlings. Environmental Toxicology, 24, 296-303.
[17]  Jyostna, V. and Sudhakar, P. (2016) Neurobehavioral Alterations in Cadmium Exposed Rats. International Journal of Recent Scientific Research, 7, 9418-9424.
[18]  Kaoud, H., Kamel, M.M., Abdel-Razek, H., Kamel, G.M. and Ahmed, K. (2010) Neurobehavioural, Neurochemical and Neuromorphological Effects of Cadmium in Male Rats. Journal of American Science, 6, 189-202.
[19]  Haider, S., Anis, L., Batool, Z., Sajid, I., Naqvi, F., Khaliq, S. and Ahmed, S. (2014) Short Term Cadmium Administration Dose Dependently Elicits Immediate Biochemical, Neurochemical and Neurobehavioral Dysfunction in Male Rats. Metabolic Brain Disease, 30, 83-92.
[20]  Carola, V., D’Olimpio, F., Brunamonti, E., Mangia, F. and Renzi, P. (2002) Evaluation of the Elevated Plus-Maze and Open-Field Tests for the Assessment of Anxiety-Related Behaviour in Inbred Mice. Behavioural Brain Research, 134, 49-57.
[21]  Gentsch, C., Lichtsteiner, M. and Feer, H. (1987) Open Field and Elevated Plus-Maze: A Behavioural Comparison between Spontaneously Hypertensive (SHR) and Wistar-Kyoto (WKY) Rats and the Effects of Chlordiazepoxide. Behavioural Brain Research, 25, 101-107.
[22]  Alicia, A. and Cheryl, A. (2007) The Use of the Elevated Plus Maze as an Assay of Anxiety-Related Behavior in Rodents. NIH Public Access, 2, 322-328.
[23]  Naranjo-Rodriguez, E.B., Osornio, A.O., Hernandez-Avitia, E., Mendoza-Fernandez, V. and Escobar, A. (2000) Anxiolytic-Like Actions of Melatonin, 5-Metoxytryptophol, 5-Hydroxytryptophol and Benzodiazepines on a Conflict Procedure. Progress in Neuro-Psychopharmacology & Biological Psychiatry, 24, 117-129.
[24]  Porsolt, R.D., Anton, G., Blavet, N. and Jalfre, M. (1978) Behavioural Despair in Rats: A New Model Sensitive to Antidepressant Treatments. European Journal of Pharmacology, 47, 379-391.
[25]  Benabid, N., Mesfioui, A. and Ouichou, A. (2008) Effects of Photoperiod Regimen on Emotional Behaviour in Two Tests for Anxiolytic Activity in Wistar Rat. Brain Research Bulletin, 75, 53-59.
[26]  Sierksma, A.S.R., Van Den Hove, D.L.A., Pfau, F., Philippens, M., Bruno, O., Fedele, E., Ricciarelli, R., Steinbusch, H.W.M., Vanmierlo, T. and Prickaerts, J. (2014) Improvement of Spatial Memory Function in APPswe/PS1dE9 Mice after Chronic Inhibition of Phosphodiesterase Type 4D. Neuropharmacology, 77, 120-130.
[27]  Morris, R. (1984) Developments of a Water-Maze Procedure for Studying Spatial Learning in the Rat. Journal of Neuroscience Methods, 11, 47-60.
[28]  Wong, A. and Brown, R.E. (1984) Age-Related Changes in Visual Acuity, Learning and Memory in C57BL/6J and DBA/2J Mice. Neurobiology of Aging, 11, 47-60.
[29]  Chao, C.C., Hu, S., Molitor, T.W., Shaskan, E.G., Peterson, P.K., Cha, C.C., Hu, S., Molitor, T.W., Shaskan, E. and Peterson, P.K. (1992) injury via a Nitric Oxide Mechanism. Activated Microglia Mediate Oxide Neuronal Cell Injury via a Nitric Mechanism. The Journal of Immunology, 149, 2736-2741.
[30]  Draper, H.H. and Hadley, M. (1990) Malondialdehyde Determination as Index of Lipid Peroxidation. Methods in Enzymology, 186, 421-431.
[31]  Freitas, R.M., Sousa, F.C.F., Vasconcelos, S.M.M., Viana, G.S.B. and Fonteles, M.M.F. (2004) Pilocarpine-Induced Status Epilepticus in Rats: Lipid Peroxidation Level, Nitrite Formation, GABAergic and Glutamatergic Receptor Alterations in the Hippocampus, Striatum and Frontal Cortex. Pharmacology Biochemistry and Behavior, 78, 327-332.
[32]  Lister, R.G. (1987) The Use of a Plus-Maze to Measure Anxiety in the Mouse. Psychopharmacology (Berl), 92, 180-185.
[33]  Abdalla, F.H., Schmatz, R., Cardoso, A.M., Carvalho, F.B., Baldissarelli, J., de Oliveira, J.S., Rosa, M.M., Gonalves Nunes, M., Rubin, M.A., da Cruz, I.B.M., Barbisan, F., Dressler, V.L., Pereira, L.B., Schetinger, M.R.C., Morsch, V.M., Gonalves, J.F. and Mazzanti, C.M. (2014) Quercetin Protects the Impairment of Memory and Anxiogenic-Like Behavior in Rats Exposed to Cadmium: Possible Involvement of the Acetylcholinesterase and Na+,K+-ATPase Activities. Physiology & Behavior, 135, 152-167.
[34]  Minetti, A. and Reale, C.A. (2006) Sensorimotor Developmental Delays and Lower Anxiety in Rats Prenatally Exposed to Cadmium. Journal of Applied Toxicology, 26, 35-41.
[35]  Méndez-Armenta, M. and Ríos, C. (2007) Cadmium Neurotoxicity. Environmental Toxicology and Pharmacology, 23, 350-358.
[36]  Goncalves, J.F., Fiorenza, A.M., Spanevello, R.M., Mazzanti, C.M., Bochi, G.V., Antes, F.G., Stefanello, N., Rubin, M.A., Dressler, V.L., Morsch, V.M. and Schetinger, M.R.C. (2010) N-Acetylcysteine Prevents Memory Deficits, the Decrease in Acetylcholinesterase Activity and Oxidative Stress in Rats Exposed to Cadmium. Chemico-Biological Interactions, 186, 53-60.
[37]  De Castro, E., Silva, E., Ferreira, H., Cunha, M., Bulcao, C., Sarmento, C., De Oliveira, J. and Fregoneze, J.B. (1996) Effect of Central Acute Administration of Cadmium on Drinking Behavior. Pharmacology Biochemistry and Behavior, 53, 687-693.
[38]  Webster, W.S. and Valois, A. (1981) The Toxic Effects of Cadmium on the Neonatal Mouse CNS. Journal of Neuropathology & Experimental Neurology, 40, 247-257.
[39]  File, S.E., Kenny, P.J. and Cheeta, S. (2000) The Role of the Dorsal Hippocampal Serotonergic and Cholinergic Systems in the Modulation of Anxiety. Pharmacology Biochemistry and Behavior, 66, 65-72.
[40]  Kamel, M.M., El Razek, A.H.A., Ahmed, K.A. and Kamel, G.M. (2011) Exposure of Adult Male Rats to Cadmium: Assessment of Sexual Behaviour, Fertility, Aggression as Well as Anxiety Like Behaviour with Special Reference to Biochemical and Pathological Alterations. Life Science Journal, 8, 106-119.
[41]  Abu-Taweel, G.M., Ajarem, J.S. and Ahmad, M. (2013) 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, 3, 74-84.
[42]  Lafuente, A., Fenández-Rey, E., Seara, R., Pérez-Lorenzo, M. and Esquifino, A.I. (2001) Alternate Cadmium Exposure Differentially Affects Amino Acid Metabo-lism within the Hypothalamus, Median Eminence, Striatum and Prefrontal Cortex of Male Rats. Neurochemistry International, 39, 187-192.
[43]  Andersson, H., Petersson-Grawé, K., Lindqvist, E., Luthman, J., Oskarsson, A. and Olson, L. (1997) Low-Level Cadmium Exposure of Lactating Rats Causes Alterations in Brain Serotonin Levels in the Offspring. Neurotoxicology and Teratology, 19, 105-115.
[44]  Lalonde, R. (2002) The Neurobiological Basis of Spontaneous Alternation. Neuroscience & Biobehavioral Reviews, 26, 91-104.
[45]  Kiraly, E. and Jones, D.G. (1982) Dendritic Spine Changes in Rat Hippocampal Pyramidal Cells after Postnatal Lead Treatment: A Golgi Study. Experimental Neurology, 77, 236-239.
[46]  Alfano, D.P. and Petit, T.L. (1982) Neonatal Lead Exposure Alters the Dendritic Development of Hippocampal Dentate Granule Cells. Experimental Neurology, 75, 275-288.
[47]  Lukawski, K., Nieradko, B. and Sieklucka-Dziuba, M. (2005) Effects of Cadmium on Memory Processes in Mice Exposed to Transient Cerebral Oligemia. Neurotoxicology and Teratology, 27, 575-584.
[48]  Méndez-Armenta, M., Barroso-Moguel, R., Villeda-Hernández, J., Nava-Ruíz, C. and Ríos, C. (2001) Histopathological Alterations in the Brain Regions of Rats after Perinatal Combined Treatment with Cadmium and Dexamethasone. Toxicology, 161, 189-199.
[49]  Skutella, T. and Nitsch, R. (2001) New Molecules for Hippocampal Development. Trends in Neurosciences, 24, 107-113.
[50]  Decker, M.W. and McGaugh, J.L. (1991) The Role of Interactions between the Cholinergic System and Other Neuromodulatory Systems in Learing and Memory, Synapse, 7, 151-168.
[51]  Flicker, C., Dean, R.L., Watkins, D.L., Fisher, S.K. and Bartus, R.T. (1983) Behavioral and Neurochemical Effects Following Neurotoxic Lesions of a Major Cholinergic Input to the Cerebral Cortex in the Rat. Pharmacology Biochemistry and Behavior, 18, 973-981.
[52]  Cory-Slechta, D.A. and Pokora, M.J. (1995) Lead-Induced Changes in Muscarinic Cholinergic Sensitivity. Neurotoxicology, 16, 337-347.
[53]  Forget, J., Pavillon, J., Beliaeff, B. and Bocquené, G. (1999) Joint Action of Pollutant Combinations (Pesticides and Metals) on Survival (LC50 Values) and Acetylcholinesterase Activity of Tigriopus brevicornis Copepoda, Harpacticoida. Environmental Toxicology and Chemistry, 18, 912-918.
[54]  Tomlinson, G., Mutus, B. and McLennan, I. (1981) Activation and Inactivation of Acetylcholinesterase by Metal Ions. Canadian Journal of Biochemistry, 59, 728-735.
[55]  Casalino, E., Sblano, C. and Landriscina, C. (1997) Enzyme Activity Alteration by Cadmium Administration to Rats: The Possibility of Iron Involvement in Lipid Peroxidation. Archives of Biochemistry and Biophysics, 346, 171-179.
[56]  Carageorgiou, H., Tzotzes, V., Sideris, A., Zarros, A. and Tsakiris, S. (2005) Cadmium Effects on Brain Acetylcholinesterase Activity and Antioxidant Status of Adult Rats: Modulation by Zinc, Calcium and L-Cysteine Co-Administration. Basic & Clinical Pharmacology & Toxicology, 97, 320-324.
[57]  Kanter, M., Unsal, C., Aktas, C. and Erboga, M. (2013) Neuroprotective Effect of Quercetin against Oxidative Damage and Neuronal Apoptosis Caused by Cadmium in Hippocampus. Toxicology and Industrial Health, 32, 541-550.
[58]  Kim, W., Kim, D.W., Yoo, D.Y., Jung, H.Y., Nam, S.M., Kim, J.W., Hong, S.-M., Kim, D.-W., Choi, J.H., Moon, S.M., Yoon, Y.S. and Hwang, I.K. (2014) Dendropanax Morbifera Léveille Extract Facilitates Cadmium Excretion and Prevents Oxidative Damage in the Hippocampus by Increasing Antioxidant Levels in Cadmium-Exposed Rats. BMC Complementary and Alternative Medicine, 14, 428.
[59]  Abdel Moneim, A.E., Bauomy, A.A., Diab, M.M.S., Shata, M.T.M., Al-Olayan, E.M. and El-Khadragy, M.F. (2014) The Protective Effect of Physalis peruviana L. against Cadmium-Induced Neurotoxicity in Rats. Biological Trace Element Research, 160, 392-399.
[60]  Mukherjee, R., Desai, F., Singh, S., Gajaria, T., Singh, P.K., Baxi, D.B., Sharma, D., Bhatnagar, M. and Ramachandran, A.V. (2010) Melatonin Protects against Alterations in Hippocampal Cholinergic System, Trace Metals and Oxidative Stress Induced by Gestational and Lactational Exposure to Cadmium. EXCLI Journal, 9, 119-132.
[61]  Karaca, S. and Eraslan, G. (2013) The Effects of Flaxseed Oil on Cadmium-Induced Oxidative Stress in Rats. Biological Trace Element Research, 155, 423-430.
[62]  Sies, H. (1997) Oxidative Stress: Oxidants and Antioxidants. Experimental Physiology, 82, 291-295.
[63]  Gaté, L., Paul, J., Ba, G.N., Tew, K.D. and Tapiero, H. (1999) Oxidative Stress Induced in Pathologies: The Role of Antioxidants. Biomedicine & Pharmacotherapy, 53, 169-180.
[64]  Thannickal, V.J. and Fanburg, B.L. (2000) Reactive Oxygen Species in Cell Signaling. American Journal of Physiology-Lung Cellular and Molecular Physiology, 279, L1005.
[65]  Hawkins, C.L. and Davies, M.J. (2001) Generation and Propagation of Radical Reactions on Proteins. Biochimica et Biophysica Acta (BBA)—Bioenergetics, 1504, 196-219.
[66]  Requena, J.R., Levine, R.L., Chao, C.-C. and Stadtman, E.R. (2001) Glutamic and Aminoadipic Semialdehydes Are the Main Carbonyl Products of Metal-Catalyzed Oxidation of Proteins. Proceedings of the National Academy of Sciences, 98, 69-74.
[67]  Yuan, X.M. and Brunk, U.T. (1998) Iron and LDL-Oxidation in Atherogenesis. APMIS, 106, 825-842.
[68]  López, E., Arce, C., Oset-Gasque, M.J., CaNadas, S. and González, M.P. (2006) Cadmium Induces Reactive Oxygen Species Generation and Lipid Peroxidation in Cortical Neurons in Culture. Free Radical Biology & Medicine, 40, 940-951.
[69]  Koizumi, T., Shirakura, H., Kumagai, H., Tatsumoto, H. and Suzuki, K.T. (1996) Mechanism of Cadmium-Induced Cytotoxicity in Rat Hepatocytes: Cadmium-Induced Active Oxygen-Related Permeability Changes of the Plasma Membrane. Toxicology, 114, 125-134.
[70]  Waisberg, M., Joseph, P., Hale, B. and Beyersmann, D. (2003) Molecular and Cellular Mechanisms of Cadmium Carcinogenesis. Toxicology, 192, 95-117.
[71]  Poliandri, A.H.B., Esquifino, A.I., Cano, P., Jiménez, V., Lafuente, A., Cardinali, D.P. and Duvilanski, B.H. (2006) In Vivo Protective Effect of Melatonin on Cadmium-Induced Changes in Redox Balance and Gene Expression in Rat Hypothalamus and Anterior Pituitary. Journal of Pineal Research, 41, 238-246.
[72]  Poliandri, A.H.B., Velardez, M.O., Cabilla, J.P., Bodo, C.C.A., MacHiavelli, L.I., Quinteros, A.F. and Duvilanski, B.H. (2004) Nitric Oxide Protects Anterior Pituitary Cells from Cadmium-Induced Apoptosis. Free Radical Biology & Medicine, 37, 1463-1471.
[73]  Gisone, P., Boveris, A.D., Dubner, D., Perez, M.R., Robello, E. and Puntarulo, S. (2003) Early Neuroprotective Effect of Nitric Oxide in Developing Rat Brain. Irradiated in Utero, 24, 245-253.
[74]  Hall, E.D., Detloff, M.R., Johnson, K., Kupina, N.C. and Al, H.E.T. (2004) Peroxynitrite-Mediated Protein Nitration and Lipid Peroxidation in a Mouse Model of Traumatic Brain Injury. Journal of Neurotrauma, 21, 9-20.
[75]  Sevanian, A. and Hochstein, P. (1985) Mechanisms and Consequences of Lipid Peroxidation in Biological Systems. Annual Review of Nutrition, 5, 365-390.
[76]  Pacifici, E.H.K., McLeod, L.L. and Sevanian, A. (1994) Lipid Hydroperoxide-Induced Peroxidation and Turnover of Endothelial Cell Phospholipids. Free Radical Biology & Medicine, 17, 297-309.
[77]  Comporti, M. (1985) Lipid Peroxidation and Cellular Damage in Toxic Liver Injury. Laboratory Investigation, 53, 599-623.
[78]  Al-Mutairi, D.A., Craik, J.D., Batinic-Haberle, I. and Benov, L.T. (2007) Induction of Oxidative Cell Damage by Photo-Treatment with Zinc N-Methylpyridylporphyrin. Free Radical Research, 41, 89-96.
[79]  Stark, G. (2005) Functional Consequences of Oxidative Membrane Damage. The Journal of Membrane Biology, 205, 1-16.
[80]  Goel, A., Dani, V. and Dhawan, D.K. (2005) Protective Effects of Zinc on Lipid Peroxidation, Antioxidant Enzymes and Hepatic Histoarchitecture in Chlorpyrifos-Induced Toxicity. Chemico-Biological Interactions, 156, 131-140.
[81]  Emerit, J., Klein, J.M., Coutellier, A. and Congy, F. (1991) Free Radicals and Lipid Peroxidation in Cell Biology: Physiopathologic Prospects. Pathologie Biologie, 39, 316-327.
[82]  Khanna, R.S., Negi, R., Pande, D., Khanna, S. and Khanna, H.D. (2012) Markers of Oxidative Stress in Generalized Anxiety Psychiatric Disorder: Therapeutic Implications. Journal of Stress Physiology & Biochemistry, 8, 32-38.
[83]  Ouakki, S., El Mrabet, F.Z., Lagbouri, I., El Hessni, A., Mesfioui, A., Pévet, P., Challet, E. and Ouichou, A. (2013) Melatonin and Diazepam Affect Anxiety-Like and Depression-Like Behavior in Wistar Rats: Possible Interaction with Central GABA Neurotransmission. Journal of Behavioral and Brain Science, 3, 522-533.
[84]  El Mrabet, F.Z., Ouakki, S., Mesfioui, A., El Hessni, A. and Ouichou, A. (2012) Pinealectomy and Exogenous Melatonin Regulate Anxiety-Like and Depressive-Like Behaviors in Male and Female Wistar Rats. Neuroscience and Medicine, 3, 394-403.
[85]  El Mrabet, F.Z., Lagbouri, I., Mesfioui, A., El Hessni, A. and Ouichou, A. (2012) The Influence of Gonadectomy on Anxiolytic and Antidepressant Effects of Melatonin in Male and Female Wistar Rats: A Possible Implication of Sex Hormones. Neuroscience and Medicine, 3, 162-173.
[86]  Edinger, K.L. and Frye, C.A. (2007) Sexual Experience of Male Rats Influences Anxiety-Like Behavior and Androgen Levels. Physiology & Behavior, 92, 443-453.
[87]  Aikey, J.L., Nyby, J.G., Anmuth, D.M. and James, P.J. (2002) Testosterone Rapidly Reduces Anxiety in Male House Mice (Mus Musculus). Hormones and Behavior, 42, 448-460.
[88]  Edinger, K.L. and Frye, C.A. (2006) Intrahippocampal Administration of an Androgen Receptor Antagonist, Flutamide, can Increase Anxiety-Like Behavior in Intact and DHT-Replaced Male Rats. Hormones and Behavior, 50, 216-222.
[89]  Elharabi, F.B. and Gatie, S.J. (2010) The Effects of Cadmium Chlorid (CdCl2) on the Functions of Reproductive System of the Male Mice. Journal of Applied Toxicology, 11, 229-235.
[90]  Dobashi, M., Fujisawa, M., Yamazaki, T., Okuda, Y., Kanzaki, M., Tatsumi, N., Tsuji, T., Okada, H. and Kamidono, S. (2001) Inhibition of Steroidogenesis in Leydig Cells by Exogenous Nitric Oxide Occurs Independently of Steroidogenic Acute Regulatory Protein (Star) mRNA. Archives of Andrology, 47, 203-209.
[91]  Nwokocha, C.R., Nwokocha, M.I., Owu, D., Edidjana, E., Nwogbo, N., Ekpo, U. and Ufearo, C.S. (2011) Estimation of Absorbed Cadmium in Tissues of Male and Female Albino Rats through Different Routes of Administration. Nigerian Journal of Physiological Sciences, 26, 97-101.
[92]  Lanszki, J., Orosz, E. and Sugár, L. (2009) Metal Levels in Tissues of Eurasian Otters (Lutra lutra) from Hungary: Variation with Sex, Age, Condition and Location. Chemosphere, 74, 741-743.
[93]  Bracken, W.M. and Klaassen, C.D. (1987) Induction of Metallothionein by Steroids in Rat Primary Hepatocyte Cultures. Toxicology and Applied Pharmacology, 87, 381-388.
[94]  Shaikh, Z.A., Jordan, S.A. and Tewari, P. (1993) Cadmium Disposition and Metallothionein Induction in Mice: Strain-, Sex-, Age-, and Dose-Dependent Differences. Toxicology, 80, 51-70.
[95]  Kara, H. (2005) Effect of Single Dose Cadmium Chloride Administration on Oxidative Stress in Male and Female Rats. Turkish Journal of Veterinary & Animal Sciences, 29, 37-42.
[96]  Zhang, W., Pang, F., Huang, Y., Yan, P. and Lin, W. (2008) Cadmium Exerts Toxic Effects on Ovarian Steroid Hormone Release in Rats. Toxicology Letters, 182, 18-23.
[97]  Johnson, M.D., Kenney, N., Stoica, A., Hilakivi-Clarke, L., Singh, B., Chepko, G., Clarke, R., Sholler, P.F., Lirio, A., Foss, C., Reiter, R., Trock, B., Paik, S. and Martin, M.B. (2003) Cadmium Mimics the In Vivo Effects of Estrogen in the Uterus and Mammary Gland. Nature Medicine, 9, 1081-1084.
[98]  Alonso-González, C., González, A., Mazarrasa, O., Güezmes, A., Sánchez-Mateos, S., Martínez-Campa, C., Cos, S., Sánchez-Barceló, E.J. and Mediavilla, M.D. (2007) Melatonin Prevents the Estrogenic Effects of Sub-Chronic Administration of Cadmium on Mice Mammary Glands and Uterus. Journal of Pineal Research, 42, 403-410.
[99]  HOfer, N., Diel, P., Wittsiepe, J., Wilhelm, M. and Degen, G.H. (2009) Dose- and Route-Dependent Hormonal Activity of the Metalloestrogen Cadmium in the Rat Uterus. Toxicology Letters, 191, 123-131.
[100]  Stoica, A., Katzenellenbogen, B.S. and Martin, M.B. (2000) Activation of Estrogen Receptor-Alpha by the Heavy Metal Cadmium. Molecular Endocrinology, 14, 545-553.


comments powered by Disqus