Generic placeholder image

CNS & Neurological Disorders - Drug Targets

Editor-in-Chief

ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

Research Article

Cytarabine and Ferric Carboxymaltose (Fe+3) Increase Oxidative Damage and Alter Serotonergic Metabolism in Brain

Author(s): David Calderón Guzmán, Norma Osnaya Brizuela, Maribel Ortíz Herrera, Hugo Juárez Olguín*, Armando Valenzuela Peraza, Ernestina Hernández García, Francisca Trujillo Jiménez and Gerardo Barragán Mejía

Volume 18, Issue 2, 2019

Page: [149 - 155] Pages: 7

DOI: 10.2174/1871527318666181128144343

Price: $65

Abstract

Background & Objective: The purpose of this study was to measure the effect on brain biomarkers after treatment with anticancer compounds - cytarabine (CT) and ferric carboxymaltose (FC) (Fe+3) in Wistar rats.

Methods: The Wistar rats were treated as follows: group 1 (control), NaCl 0.9%; group 2, CT (25 mg/k), group 3, FC(Fe+3) (50 mg/k) and group 4, CT + FC(Fe+3). The animals were sacrificed and their brains were obtained and used to measure lipoperoxidation (TBARS), H2O2, Na+, K+ ATPase, glutathione (GSH), serotonin metabolite (5-HIAA) and dopamine. The results indicated an enhancement of lipid peroxidation in the cortex and striatum of groups treated with FC(Fe+3) and CT, while GSH decreased in the cortex of group treated with CT + FC(Fe+3). Dopamine decreased in the cortex of the rats that received CT, while in the striatum, 5HIAA increased in all groups.

Results & Conclusion: These results suggest that the treatment with CT and FC(Fe+3) boosted oxidative stress and led to an alteration in momoamine concentrations in the brain.

Keywords: Iron, oxidative damage, brain, anticancer agents, oncological diseases, malignant tumor.

[1]
The incidence of cancer in children increases www.genero y salud. reproductiva.gob.mx/article2006.
[2]
Ross JA, Severson RK, Pollock BH, Robison LL. Childhood cancer in the Unites States. A geographical analysis of cases from the Pediatric Cooperative Clinical Trials groups. Cancer 1996; 77: 201-7.
[3]
Cavaliere R, Schiff D. Neurologic toxicities of cancer therapies. Curr Neurol Neurosci Rep 2006; 6: 218-26.
[4]
Matsutani T, Tamaru M, Hayakawa Y, Nagayoshi M, Nakahara T, Tsukada Y. A neurochemical study of developmental impairment of the brain caused by the administration of cytosine arabinoside during the fetal or neonatal period of rats. Neurochem Res 1983; 8: 1295-306.
[5]
The Merck Manual of Diagnosis and Therapy. Eighteenth Edition. Merck & Co. INC. NJ. USA. 2005..
[6]
Barni S, Gascòn P, Petrelli F. Position paper on management of iron deficiency in adult cancer patients. Expert Rev Hematol 2017; 10: 685-95.
[7]
Gritsaev SV, Shikhbabaeva DI, Rybakova LP, Sergeev AN, Kapustin SI, Abdulkadyrov KM. Time course of changes in iron metabolic and oxidative-antioxidative system parameters in patients with Acute Myeloid Leukemia. Ter Arkh 2013; 85: 60-5.
[8]
Hogg N, Singh RJ, Kalyanaraman B. The role of glutathione in the transport and catabolism of nitric oxide. FEBS Lett 1996; 382: 223-8.
[9]
Beckman JS, Beckman TW, Chen J, Marshall PA, Freeman BA. Apparent hydroxyl radical production by peroxynitrite: Implications for endothelial injury from nitric oxide and superoxides. Proc Natl Acad Sci USA 1990; 87: 1624-9.
[10]
Gutteridge JM, Halliwell B. The measurement and mechanism of lipid peroxidation in biological systems Trends Biochem Sci1 990; 15: 129-35
[11]
Driver AS, Kodavanti PR, Mundy WR. Age-related changes in reactive oxygen species production in rat brain homogenates. Neurotoxicol Teratol 2000; 22: 175-81.
[12]
Shamitko-Klingensmith N, Molchanoff KM, Burke KA, Magnone GJ, Legleiter J. Mapping the mechanical properties of cholesterol-containing supported lipid bilayers with nanoscale spatial resolution. Langmuir 2012; 28: 13411-22.
[13]
Vogt MC, Brüning JC. CNS insulin signaling in the control of energy homeostasis and glucose metabolism - from embryo to old age. Trends Endocrinol Metab 2013; 24: 76-84.
[14]
Swapna I, Sathya KV, Murthy CR, Senthilkumaran B. Membrane alterations and fluidity changes in cerebral cortex during ammonia intoxication. Neuro Toxicol 2005; 335: 700-4.
[15]
Stefanello FM, Chiarani F, Kurek AG. Methionine alters Na+, K+ ATPase activity, lipid peroxidation and nonenzymatic antioxidant defenses in rat hippocampus. Int J Dev Neurosci 2005; 23: 651-6.
[16]
Calderon GD, Juarez OH, Hernandez GE, et al. Effect of an antiviral and vitamins A, C, D on dopamine and some oxidative stress markers in rat brain exposed to ozone. Arch Biol SciBelgrade 2013; 65: 1371-9.
[17]
Hissin PJ, Hilf R. A flurometric method for determination of oxidized and reduced glutathione in tissue. Anal Biochem 1974; 4: 214-26.
[18]
Asru KS. Colorimetric assay of catalase. Anal Biochem 1972; 47: 389-94.
[19]
Calderón GD, Osnaya BN, García AR, Hernández GE, Guillé PA. Levels of glutathione and some biogenic amines in the human brain putamen after traumatic death. Proc West Pharmacol Soc 2008; 51: 25-32.
[20]
Beck O, Palmskog G, Hultman E. Quantitative determination of 5-hydroxyindole-3-acetic acid in body fluids by HPLC. Clin Chim Acta 1977; 79: 149-54.
[21]
Calderon-Guzman D, Espitia-Vázquez I, López-Domínguez A, Hernández-García E, Huerta-Gertrudis B, Juárez-Olguín H. Effect of toluene and nutritional status on serotonin, lipid peroxidation levels and Na+/K+ATPase in adult rat brain. Neurochem Res 2005; 30: 619-24.
[22]
Fiske CH, Subbarow Y. The colorimetric determination of phosphorus. J Biol Chem 1972; 66: 375-400.
[23]
Rem J, Siggaard-Andersen O, Norgaard-Pedersen B, Sorensen S. Hemoglobin pigments. Photometer for oxygen saturation, carboxyhemoglobin, and methemoglobin in capillary blood. Clin Chim Acta 1972; 42: 101-8.
[24]
Toledano A, Luporsi E, Morere JF, et al. Clinical use of ferric carboxymaltose in patients with solid tumours or haematological malignancies in France. Support Care Cancer 2016; 24: 67-75.
[25]
Toblli JE, Rivas C, Cao G, et al. Ferric carboxymaltose-mediated attenuation of doxorubicin-induced cardiotoxicity in an iron deficiency rat model. Chemother Res Pract 2014; 570241.
[26]
Toblli JE, Cao G, Giani JF, Dominici FP, Angerosa M. Markers of oxidative/nitrosative stress and inflammation in lung tissue of rats exposed to different intravenous iron compounds. Drug Des Devel Ther 2017; 11: 2251-63.
[27]
Yoo SJ, Cho B, Moon C, Yu SW, Moon C. Neuroprotective effects of an erythropoietin-derived peptide in pc1 2 cells under oxidative stress. CNS Neurol Disord Drug Targets 2016; 15(8): 927-34.
[28]
Hossain S, Akaike T, Chowdhury EH. Current approaches for drug delivery to central nervous system. Curr Drug Deliv 2010; 7: 389-97.
[29]
de Farias CC, Maes M, Bonifacio KL, et al. Parkinson’s disease is accompanied by intertwined alterations in iron metabolism and activated immune-inflammatory and oxidative stress pathways. CNS Neurol Disord Drug Targets 2017; 16(4): 484-91.
[30]
Calderón GD, Osnaya BN, Ortíz HM. Oleic acid protects against oxidative stress exacerbated by cytarabine and doxorubicin in rat brain. Anti-Cancer Ag Me 2016; 16: 1491-5.
[31]
Calderón GD, Ortiz HM, Valenzuela PA, et al. Biochemical and histological changes produced by sweeteners and cytarabine in brain of young rats. Nutr Hosp 2018; 35: 194-200.
[32]
Steinmetz T, Tschechne B, Harlin O. Clinical experience with ferric carboxymaltose in the treatment of cancer- and chemotherapy-associated anaemia. Ann Oncol 2013; 24: 475-82.
[33]
Popa-Wagner A, Mitran S, Sivanesan S, Chang E, Buga AM. ROS and brain diseases: the good, the bad, and the ugly. Oxid Med Cell Longev 2013; 2013: 963520.
[34]
Saedisomeolia A, Samadi M, Gholami F, et al. Vitamin D’s molecular action mechanism in attention-deficit/ hyperactivity disorder: A review of evidence. CNS Neurol Disord Drug Targets 2018; 17(4): 280-90.

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy