Doxorrubicina e chemobrain - Estudos experimentais para a avaliação dos déficits cognitivos pós-quimioterapia

Autores

  • Carolina Vieira Cardoso Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo (SP), Brasil
  • Eduardo Fernandes Bondan Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo (SP), Brasil

Palavras-chave:

chemobrain, déficits cognitivos, doxorrubicina, estudos experimentais, quimioterapia

Resumo

A doxorrubicina (DOX), um agente interativo da topoisomerase, é comumente utilizada no tratamento de vários tipos de câncer sólidos e hematológicos. Esta droga é conhecida por causar prejuí­zos cognitivos em indiví­duos submetidos à quimioterapia de longo prazo (déficits também chamados de chemobrain). Frente à relativa inexistência de estratégias preventivas ou terapêuticas eficazes para evitar o desenvolvimento do chemobrain, modelos experimentais in vitro e in vivo têm sido empregados na busca da compreensão dos mecanismos subjacentes a tal fenômeno.  A presente revisão visa a apresentar estudos envolvendo a administração de DOX, como base para o possí­vel entendimento dos processos que conduzem aos prejuí­zos cognitivos induzidos pela quimioterapia.

Biografia do Autor

Carolina Vieira Cardoso, Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo (SP), Brasil

Médica Veterinária formada pela Universidade Paulista (UNIP) e mestranda do Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo (SP), Brasil.

Eduardo Fernandes Bondan, Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo (SP), Brasil

Médico Veterinário pela Universidade Federal de Pelotas (UFPel); Doutor em Patologia Experimental e Comparada (USP); Professor titular do Programa de Pós-Graduação em Patologia Ambiental e Experimental, Universidade Paulista (UNIP), São Paulo (SP), Brasil.

Referências

Abba JK, Akerstrom V, Pan W. Interleukin-10 as a CNS therapeutic: the obstacle of the blood-brain/blood-spinal cord barrier. Mol Brain Res. 2003; 114: 168-171.

Ahles TA, Saykin JA. Candidates mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 2007; 3: 192-201.

Ahles TA, Root JC, Ryan EL. Cancer- and cancer treatment- associated cognitive change: an update on the state of the science. J Clin Oncol. 2012; 30: 3675-3686.

Aluise CD, Sultana R, Tangpong J, Vore M, St Clair D, Moscow JA, Butterfield DA. Chemo brain (chemo fog) as a potential side effect of doxorubicin administration: role of cytokine-induced, oxidative/nitrosative stress in cognitive dysfunction. Adv Exp Med Biol. 2010; 678: 157-156.

Bains OS, Szeitz A, Lubieniecka JM, Cragg GE, Grigliatti AT, Riggs WK, Reid ER. A correlation between cytotoxicity and reductase-mediated metabolism in cell lines treated with doxorubicin and daunorubicin. J Pharmacol Exp Ther. 2013; 347: 375-387.

Banks WA. Blood-brain barrier transport of cytokines: a mechanism for neuropathology. Curr Pharm Des. 2005; 11: 973-984.

Brennan FX, Beck KD, Servatius RJ. Low doses of interleukin-1ß improve the leverpress avoidance performance of Sprague-Dawley rats. Neurobiol Learn Mem. 2003; 80: 168-171.

Boykoff N, Moeini M, Subramanian SK. Confronting chemobrain: an in-depth look at survivors"™ reports of impact on work, social networks, and health care response. J Cancer Surviv. 2009; 3: 223-232.

Butterfield DA. The 2013 discovery award from the society for free radical biology and medicine: Selected discoveries from the Butterfield Laboratory of oxidative stress and its sequelae in brain in cognitive disorders exemplified by Alzheimer disease and chemotherapy induced cognitive impairment. Free Radic Biol Med. 2014; 1: 157-174.

Ciernia VA, Wood AM. Examining object location and object recognition memory in mice. Behavi Neurosci. 2014; 69: 8-31.

Cullinane C, Cutts SM, Panousis C, Phillips DR (2000) Interstrand cross-linking by adriamycin in nuclear and mitochondrial DNA of MCF-7 cells. Nucleic Acids Res 28: 1019-1025.

Cutts SM, Nudelman A, Rephaeli A, Phillips DR. The power and potential of doxorubicin-DNA adducts. IUBMB Life 2005; 57: 73-81.

Cutsuridí­s V, Yoshida M. Editorial: memory processes in medial temporal lobe: experimental, theoretical and computational approaches. Front Syst Neurosci. 2017; 11: 1-3.

Deeken JF, Loscher W. The blood-brain barrier and cancer: transporters, treatment, and Trojan horses. Clin Cancer Res. 2007; 13: 1663-1674.

Fojtu M, Gumulec J, Raudenska M, Skatakova A, Vaculovicova M, Adam V, Babula P, Novakova M, Masarik M. Reduction of doxorubicin-induced cardiotoxicity using nanocarriers: A review. Curr Drug Metabol. 2017; 18: 12.

Forrest A, Swift LP, Rephaeli A, Nudelman A, Kimura K, Phillips DR, Cutts SM. Activation of DNA damage response pathways as a consequence of anthracycline-DNA adduct formation. Biochem Pharmacol. 2012; 83: 1602-1612.

Gaman MA, Uzoni A, Popa-Wagner A, Andrei A, Petcu BE. The role of oxidative stress in etiopathogenesis of chemotherapy induced cognitive impairment (CICI) - "chemobrain". Aging Dis. 2016; 1: 302-312.

Gewirtz DA. A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics adriamycin and daunorubicin. Biochem Pharmacol. 1999; 57: 727-741.

Gutierrez LP. The metabolism of quinone-containing alkylating agents: free radical production and measurement. Front Biosci. 2000; 5: 629-638.

Halle CF, Moore MD. An overview of chemotherapy-related cognitive dysfunction, or "chemobrain". Oncology (Williston Park) 2014; 9: 797-804.

Holden MJ, Overmier BJ, Cowan TE, Matthews L. Effects of lipopolysaccharide on consolidation of partial learning in the Y-maze. Integr Physiol Behav Sci. 2004; 39: 334-340.

Holley AK, Miao L, St Clair DK, St Clair WH. Redox-modulated phenomena and radiation therapy: the central role of superoxide dismutases. Antioxid Redox Signal. 2014; 20: 1567-1589.

Hurria A, Somlo G, Ahles T. Renaming "chemobrain". Cancer Invest. 2007; 6: 373-377.

Iyevleva AG, Imyanitov EN. Cytotoxic and targeted therapy for hereditary cancers. Hered Cancer Clin Pract. 2016; 1: 14-17.

Janelsins CM, Kohli S, Mohile GS, Usuki K, Ahles AT, Morrow RG. An update on cancer- and chemotherapy-related cognitive dysfunction: current status. Semin Oncol. 2012; 38: 431-438.

Kaiser J, Bledowski C, Dietrich J. Neural correlates of chemotherapy-related cognitive impairment. Cortex 2014; 54: 33-50.

Kesler S, Janelsins M, Koovakkattu D, Palesh O, Mustian K, Morrow G, Dhabhar FS. Reduced hippocampal volume and verbal memory performance associated with interleukin-6 and tumor necrosis factor-alpha levels in chemotherapy-treated breast cancer survivors. Brain Behav Immun. 2013; 30: s109-s116.

Konat GW, Kraszpulski M, James I, Zhang TH, Abraham J. Cognitive dysfunction induced by chronic administration of common cancer chemotherapeutics in rats. Metab Brain Dis. 2008; 23: 325-333.

Konsman JP, Vigues S, Mackerlova L, Bristow A, Blomqvist A. Rat brain vascular distribution of inteleukin-1 type-1 receptor immunoreactivity: relationship of patterns of inducible cyclooxygenase expression by peripheral inflammatory stimuli. J Comp Neurol. 2004; 472: 113-119.

Koppelmans V, Breteler MBM, Boogerd W, Seynaeve C, Schagen B S. Late effects of adjuvant chemotherapy for adult onset non-CNS cancer; cognitive impairment, brain structure and risk of dementia. Oncol Hematol. 2013; 88: 87-101.

Kosoko AM, Olurinde OJ, Akinloye OA. Doxorubicin induced neuro- and cardiotoxicities in experimental rats: Protection against oxidative damage by Theobroma cacao Sterm bark. Biochem Biophys Rep. 2017; 10: 303-317.

Lu PYL, Ramanan N. A critical cell-intrinsic role for serum response factor in glial specification in the CNS. J Neurosci. 2012; 23: 8012-8023.

McDonald CB, Saykin JA. Alterations in brain structure related to breast cancer and its treatment: Chemotherapy and other considerations. Brain Imaging Behav. 2014; 4: 2-23.

McGowan JC, Chung R, Maulik A, Piotrowska I, Walker MJ, Yellon MD. Anthracycline chemotherapy and cardiotoxicity. Cardiovasc Drugs Ther. 2017; 31: 63-75.

Menna P, Paz OG, Chello M, Covino E, Salvatorelli E, Minotti G. Anthracycline cardiotoxicity. Exp Opin Drug Saf. 2012; 11: 21-36.

Merzoug S, Toumi ML, Boukhris N, Baudin B, Tahraoui A. Adriamycin-related anxiety-like behavior, brain oxidative stress and myelotoxicity in male Wistar rats. Pharmacol Biochem Behav. 2011; 99: 639-647.

Meyers CA. How chemotherapy damages the central nervous system. J Biol. 2008; 7: 1-11.

Mohamed HE, Asker ME, Ali SI, El-Fattah TM. Protection against doxorubicin cardiomyopathy in rats: role of phosphodiesterase inhibitors type 4. J Pharm Pharmacol. 2004; 56: 757-768.

Moore HFC. An overview of chemotherapy-related cognitive dysfunction, or "˜chemobrain"™. Oncology 2014; 28: 797-804.

Moruno-Manchon JF, Dabaghian Y, Uzor NE, Kesler SR, Wefel JS, Tsvetkov AS. Levetiracetam mitigates doxorubicin-induced DNA and synaptic damage in neurons. Sci Rep. 2016a; 25705: 1-12.

Moruno-Manchon, JF.; Uzor NE, Kesler SR, Wefel JS, Townley DM, Nagaraja AS, Pradeep S, Mangala LS, Sood AK, Tsvetkov AS. TFEB ameliorates the impairment of the autophagy-lysosome pathway in neurons induced by doxorubicin. Aging 2016b; 8: 3507-3519.

Myers JS. The possible role of cytokines in chemotherapy-induced cognitive deficits. Adv Exp Med Biol. 2010; 678: 119-123.

Nitiss JL. Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer 2009; 9: 338-350.

Ojha S, Taee AH, Goyal S, Mahajan UB, Patil CR, Arya DS, Rajesh M. Cardioprotective potentials of plant-derived small molecules against doxorubicin associated cardiotoxicity. Oxid Med Cel Longev. 2016; 23: 1-19.

Pendergrass CJ, Targum DS, Harrison EJ. Cognitive impairment associated with cancer: a brief review. Innov Clin Neurosci. 2017; 15: 36-44.

Pekny M, Pekna M. Astrocyte intermediate filaments in CNS pathologies and regeneration. J Pathol. 2004; 204: 428-437.

Pierre J, McDonald BC. Neuroepidemiology of cancer and treatment-related neurocognitive dysfunction in adult-onset cancer patients and survivors. Handb Clin Neurol. 2016; 138: 297-309.

Rahman I, Kode A, Biswas SK. Assay for quantitative determination of glutathione and glutathione disulfide levels using enzymatic recycling method. Nat Prot. 2007; 1: 3159-3165.

Ramalingayya GV, Nayak PG, Shenoy RR, Rao CM, Nandakumar K. Female rats induced with mammary cancer as a relevant animal model for doxorubicin-induced chemobrain in vivo. Clin Exp Pharmacol Physiol. 2016; 43: 862-863.

Seigers R, Loss M, Tellingem V, Boogerdd W, Smit AB, Schagen ESB. Neurobiological changes by cytotoxic agents in mice. Behav Brain Res. 2016; 299: 19-26.

Simó M, Rifí -Ros X, Fornells RA, Bruna J. Chemobrain: A systematic review of structural and functional neuroimaging studies. Neurosc Biobehav Rev. 2013; 37: 1311-1321.

Sinha BK, Mason RP. Is metabolic activation of topoisomerase II poisons important in the mechanism of cytotoxicity? J Drug Metabol Toxicol. 2015; 6: 1-8.

Stefanini S, Chiancone E, Antonini E. Iron binding to apoferritin: a fluorescence spectroscopy study. FEBS Lett. 1976; 69: 90-94.

Stone BJ, DeAngelis ML. Cancer treatment-induced neurotoxicity: a focus on newer treatments. Nat Rev Clin Oncol. 2016; 13: 92-105.

Taillibert S, Rhun EL, Chamberlain MC. Chemotherapy-related neurotoxicity. Curr Neurol Neurosci Rep. 2016; 16: 3-14.

Tangpong J, Miriyala S, Noel T, Sinthupibuluakit C, Jungsuwadee P, St-Clair KD. Doxorubicin-induced central nervous system toxicity and protection by xanthone derivative of Garcinia mangostana. Neurosci. 2011; 175: 292-299.

Tim AA, Andrew JS. Candidate mechanisms for chemotherapy-induced cognitive changes. Nat Rev Cancer 2007; 7: 192-201.

Vardi J, Tannock I. Cognitive function after chemotherapy in adults with solid tumours. Crit Rev Oncol Hematol. 2007; 63: 183-202.

Wang JC. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cel Biol. 2002; 3: 430-440.

Wang L, Chen Q, Haixia Q, Wang C, Wang C, Zhang J, Dong L. doxorubicin-induced systemic inflammation is driven by upregulation of toll-like receptor TLR4 and endotoxin leakage. Cancer Res. 2016; 76: 6631-6642.

Wang XM. Walitt B, Saligan L, Tiwari AF, Cheung CW. Chemobrain: A critical review and causal hypothesis of link between cytokines and epigenetic reprogramming associated with chemotherapy. Cytokine 2015; 72: 86-96.

Weiss RB. The anthracyclines: will we find a better doxorubicin? Semin Oncol. 1992; 19: 670-686.

Wigmore P. The effect of systemic chemotherapy on neurogenesis, plasticity and memory. Curr Top Behav Neurosci. 2012; 15: 211-240.

Wohlfart S, Khalansky A, Gelperina S, Maksimenki O, Bernreuther C, Glatzel M, Kreuter J. Efficient chemotherapy of rat glioblastoma using doxorubicin-loaded PLGA nanoparticles with different stabilizers. PLoS One 2011; e19121: 1-8.

Yang Z, Wang KW. Glial fibrillary acidic protein: From intermediate filament assembly and gliosis to neurobiomarker. Trends Neurosci. 2015; 38: 364-374.

Yirmiya R, Winocur G, Goshen I. Brain interleukin-1 is involved in spatial memory and passive avoidance conditioning. Neurobiol Learn Mem. 2002; 78: 379-389.

Downloads

Publicado

2018-11-09

Edição

v. 6 (2018)

Seção

Revisão

Licença

Autores que publicam nesta revista mantêm os direitos autorais e concedem à revista o direito de primeira publicação, com o trabalho simultaneamente licenciado sob a Licença Creative Commons Attribution que permite o compartilhamento do trabalho com reconhecimento da autoria e publicação inicial nesta revista.

Autores têm autorização para assumir contratos adicionais separadamente, para distribuição não-exclusiva da versão do trabalho publicada nesta revista (ex.: publicar em repositório institucional ou como capí­tulo de livro), com reconhecimento de autoria e publicação inicial nesta revista.