Abstract
Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 μg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.
Similar content being viewed by others
References
Santos DB, Schiara VPP, Ribeiro MCP, Schwaba RS, Meinerza DF, Allebrandta J, Rocha JBT, Nogueira CW, Aschnerb M, Barbosa NBV (2009) Genotoxicity of organoselenium compounds in human leukocytes in vitro. Mutat Res 676:21–26
Braga AL, Zeni G, Andrade LH, Silveira CC (1997) Stereoconservative formation and reativity of α-chalcogen-functionalized vinylithium coumpounds from bromo-vinylic chalcogens. Synlett 5:595–596
Paulmier C (1986) Selenium reagents and intermediates. Organic Synthesis, Pergamon
Arner ES (2009) Focus on mammalian thioredoxin reductases—important selenoproteins with versatile functions. Biochim Biophys Acta 1790(6):495–526
Vinceti M, Maraldi T, Bergomi M, Malagoli C (2009) Risk of chronic low-dose selenium overexposure in humans: insights from epidemiology and biochemistry. Rev Environ Health 24:231–248
Chasteen TG, Bentley R (2003) Biomethylation of selenium and tellurium: microorganisms and plants. Chem Rev 103:1–25
Burger ME, Fachinetto R, Zeni G, Rocha JBT (2005) Ebselen attenuates haloperidol-induced orofacial dyskinesia and oxidative stress in rat brain. Pharma Biochem Beh 81:608–615
Ghisleni G, Porciúncula LO, Cimarostia H, Rocha JBT, Salbego CG, Souza DO (2003) Diphenyl diselenide protects rat hippocampal slices submitted to oxygen–glucose deprivation and diminishes inducible nitric oxide synthase immunocontent. Brain Res 986:196–199
Müller A, Cadenas E, Graf P, Sies H (1984) A novel biologically active selenoorganic compound. I. Glutathione peroxidase-like activity in vitro and antioxidant capacity of PZ51 (ebselen). Biochem Pharmacol 33:3235–3239
Nogueira CW, Quinhones EB, Jung EAC, Zeni G, Rocha JBT (2003) Anti-inflammatory and antinociceptive activity of diphenyl diselenide. Inflamm 52:56–63
Nogueira CW, Zeni G, Rocha JBT (2004) Organoselenium and organotellurium compounds: toxicology and pharmacology. Chem Rev 104:6255–6286
Halliwell B (2009) Free radicals and antioxidants: a personal view. Nutr Rev 52:253–265
Lee SR, Suh SI, Kim SP (2000) Protective effects of the green tea polyphenol (2)-epigallocatechin gallate against hippocampal neuronal damage after transient global ischemia in gerbils. Neurosci Lett 287:191–194
Butterfield DA, Kanski J (2001) Brain protein oxidation in age-related neurodegenerative disorders that are associated with aggregated proteins. Mech Ageing Dev 122:945–962
Stadtman ER (1990) Metal ion-catalyzed oxidation of proteins: Biochemical mechanism and biological consequences. Free Radic Biol Med 9:315–325
Gabbita SP, Lovell MA, Markesbery WR (1998) Increased nuclear DNA oxidation in the brain in Alzheimer’s disease. J Neurochem 71:2034–2040
Mecocci PL, MacGarvey U, Beal MF (1994) Oxidative damage to mitochondrial DNA is increased in Alzheimer’s disease. Ann Neurol 36:747–750
Smith MA, Perry G, Richey PL, Sayre LM, Anderson VE, Beal MF, Kowall N (1996) Oxidative damage in Alzheimer’s disease. Nature 382:120–121
Zeni G, Braga AL, Stefani HA (2003) Palladium-catalyzed coupling of sp2-hybrized tellurides. Accounts Chem Res 36:718–731
Silveira CC, Braga AL, Guerra RB (2002) Stereoselective synthesis of alpha-phenylchalcogeno-alpha, beta-unsaturated esters. Tetrahedron Lett 43:3395–3397
Ohkawa H, Ohishi N, Yagi K (1979) Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal Biochem 95:351–358
Reznick AZ, Packer L (1994) Carbonyl assay for determination of oxidatively modified proteins. Meth Enzymol 233:357–363
Aksenov MY, Markesbery WR (2001) Change in thiol content and expression of glutathione redox system gene in the hippocampus and cerebellum in Alzheimer’s disease. Neurosci Lett 302:141–145
Marklund S (1985) Handbook of methods for oxygen radical research. CRC Press, Boca Raton, pp 243–247
Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126
Flohe L, Gunzler WA (1984) Assays of glutathione peroxidase. Methods Enzymol 105:114–121
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–267
Zeni G, Ludtke D, Panatieri RB, Braga AL (2006) Vinylic tellurides: from preparation to their applicability in organic synthesis. Chem Rev 106:1032–1076
Bondy SC (1997) Free radical mediated toxic injury to the nervous system. In: Wallace KB (ed) Free radical toxicology. Taylor & Francis, Oxford, pp 221–248
Weber GF (1994) The pathophysiology of reactive oxygen intermediates in the central nervous system. Med Hypotheses 43(4):223–230
Baek BS, Kwon HJ, Lee KH, Yoo MA, Kim KW, Ikeno Y, Yu BP, Chung HY (1999) Regional difference of ROS generation, lipid peroxidation, and antioxidant enzyme activity in rat brain and their dietary modulation. Arch Pharm Res 22:361–366
Gemelli T, Carvalho CA, de Andrade RB, Guerra RB, Oliboni L, Salvador M, Dani C, Funchal C (2011) The organochalcogen 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one induces oxidative stress in heart, liver, and kidney of rats. Mol Cell Biochem. doi:10.1007/s11010-011-0850-1
Funchal C, Carvalho CAS, Gemelli T, Centeno AS, Guerra RB, Salvador M, Dani C, Coitinho A, Gomez R (2010) Effects of acute Administration of 3-butyl-1-phenyl-2-(Phenyltelluro)oct-em-1-one on oxidative stress in cerebral córtex, hippocampus, and cerebellum of rats. Cell Mol Neurobiol 30:1135–1142
Hassan W, Pinton S, Rocha JT, Deobald AM, Braga AL, Nogueira CW, Latini AS, Rocha JB (2011) Hydroxyl containing seleno-imine compound exhibits improved anti-oxidant potential and does not inhibit thiol-containing enzymes. Chem Biol Interact 1:35–44
Ineu RP, Pereira M, Aschner M, Nogueira C, Zeni G, Rocha J (2008) Diphenyl diselenide reverses gastric lesions in rats: involvement of oxidative stress. Food Chem Toxicol 46:3023–3029
Abdalla DSP, Lima ES (2001) Peroxidação Lipídica: mecanismos e avaliação em amostras biológicas. Rev Bras Cienc Farm 37(3):293–303
Tappel AL (1973) Lipid peroxidation damage to cell components. Fed Proc 32:1870–1874
Penz J, Gemelli T, Carvalho CAS, Guerra RB, Olibone L, Salvador M, Dani D, Araujo AS, Funchal C (2009) Effect of 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on oxidative stress in cerebral cortex of rats. Food Chem Toxicol 47:745–751
Carvalho CA, Gemelli T, Guerra RB, Oliboni L, Salvador M, Dani C, Araujo AS, Mascarenhas M, Funchal C (2009) Effect of in vitro exposure of human serum to 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one on oxidative stress. Mol Cell Biochem 332:127–134
Zugno AI, Stefanello FM, Scherer EBS, Mattos C, Pederzolli CD, Andrade VM, Wannmacher CMD, Wajner M, Dutra-Filho CS, Wyse ATS (2008) Guanidinoacetate decreases antioxidant defenses and total protein sulfhydryl content in striatum of rats. Neurochem Res 33:1804–1810
Nogueira CW, Borges VC, Zeni G, Rocha JB (2003) Organochalcogens effects on delta-aminolevulinate dehydratase activity from human erythrocytic cells in vitro. Toxicology 191:169–178
Bechara EJH, Medeiros MHG, Monteiro HP, Hermes-Lima M, Pereira B, Demasi M, Costa C, Adballa DSP, Onuki J, Wendel CMA, Masci PD (1993) A free radical hypothesis of lead poisoning and in born porphyrias associated with 5-aminolevulinic overload. Quimica Nova 16:385–392
Emanuelli T, Pagel FW, Alves LB, Regner A, Souza DO (2001) Inhibition of adenylate cyclase activity by 5-aminolevulinic acid in rat and human brain. Neurochem Int 38:213–218
Björnstedt M, Odlander B, Kuprin S, Claesson HE, Holmgrem A (1996) Selenite incubated with NADPH and mammalian thioredoxin reductase yields selenide, which inhibits lipoxygenase and changes the electron spin resonance spectrum of the active site iron. Biochemistry 35:8511–8516
Park HS, Park E, Kim MS, Ahn K, Kim IY, Choi EJ (2000) Selenite inhibits the c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) through a thiol redox mechanism. J Biol Chem 275:2527–2531
Borges VC, Rocha JB, Nogueira CW (2005) Effect of diphenyl diselenide, diphenyl ditelluride and ebselen on cerebral Na(+), K(+)-ATPase activity in rats. Toxicology 215:191–197
Andrade RB, Gemelli T, Guerra RB, Funchal C, Wannmacherb CMD (2010) Inhibition of creatine kinase activity by 3-butyl-1-phenyl-2-(phenyltelluro)oct-en-1-one in the cerebral cortex and cerebellum of young rats. J Appl Toxicol 30:611–616
Halliwell B (2001) Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. Drugs Aging 18:685–716
Remacle J, Michiels C, Raes M (1992) The importance of antioxidant enzymes in cellular aging and degeneration. EXS 62:99–108
Halliwell B, Gutteridge JMC (2007) Measurement of reactive species. Oxford University Press, Oxford
Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J (2007) Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol 39:44–84
Benzi G, Moretti A (1995) Age and peroxidative stress related modifications of the cerebral enzymatic activities linked to mitochondria and glutathione system. Free Radic Biol Med 19:77–101
Sies H (1991) Oxidative stress: from basic research to clinical application. Am J Med 91:31–38
Acknowledgments
This work was supported by Centro Universitário Metodista do IPA and CNPq.
Conflict of interest
All authors declare that they have no conflicts of interest in this study.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Medeiros, M.C., Mello, A., Gemelli, T. et al. Effect of Chronic Administration of the Vinyl Chalcogenide 3-Methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on Oxidative Stress in Different Brain Areas of Rats. Neurochem Res 37, 928–934 (2012). https://doi.org/10.1007/s11064-011-0685-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-011-0685-x