Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína
Autor(a) principal: | |
---|---|
Data de Publicação: | 2020 |
Tipo de documento: | Dissertação |
Idioma: | por |
Título da fonte: | Biblioteca de teses e dissertações da Universidade de Passo Fundo (BDTD UPF) |
Texto Completo: | http://tede.upf.br:8080/jspui/handle/tede/2045 |
Resumo: | Methylphenidate (MPH) is a psychostimulant widely prescribed for the Treatment of Attention Deficit Hyperactivity Disorder (ADHD), since it decreases motor restlessness and promotes increased concentration, attention and memory. However, due to its stimulating effects, MPH has been used as an easily accessible drug of abuse, cognitive enhancer and can be added in dietary supplements, along with other stimulants, the most prevalent being caffeine (CAF). The effects of this irregular and abusive use of MPH are not yet fully understood. The main objective of this work was to evaluate the toxic effects of MPH, used acutely and in non-therapeutic doses, isolated or associated with CAF, through behavioral tests, oxidative stress markers and parameters of the mitochondrial respiratory chain, using zebrafish as an animal model. Fish were exposed for 15 minutes to 3 different doses: MPH 80 (80 mg / L), CAF 150 (150 mg / L) and MPH80 + CAF150 (80 mg / L + 150 mg / L). After exposure, exploratory behavior, social preference and memory were evaluated. The following mechanisms related to the observed changes were investigated: oxidative stress markers (lipid peroxidation, non-protein thiols, protein carbonylation), nitric oxide generation, protein level and energy status parameters (activity of mitochondrial complexes I, II-III and IV). We demonstrated that MPH used in an abusive way promotes antisocial behavior and induces protein carbonylation. Regarding the oxidative effects, isolated MPH had a protective effect, inhibiting lipid peroxidation. CAF used alone promotes an increase in the activities of the mitochondrial respiratory complexes (II-III and IV) and the generation of nitric oxide. The association of MPH and CAF in the non-therapeutic context promotes anxiogenic behavior and memory impairment. Although this association decreases lipid peroxidation, it promotes an increase in protein carbonylation, in addition to an increase in the activities of mitochondrial respiratory complexes (II-III and IV). Our results show that the nontherapeutic exposure of MPH and CAF has relevant effects on sociability and anxiety behavior. The association impairs memory. Mechanisms related to these changes are related to protein lesion, as evidenced by increases in protein carbonylation, as well as increases in mitochondrial metabolism. |
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Grando, Luciana Grazziotin Rossato00531009050http://lattes.cnpq.br/4915700374200518Barcellos, Leonardo José Gil67458491000http://lattes.cnpq.br/450448263491154600475683056http://lattes.cnpq.br/1475258536527110Freddo, Natália2021-05-31T19:52:20Z2020-07-28FREDDO, Natália. Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína. 2020. 62 f. Dissertação (Mestrado em Bioexperimentação) - Universidade de Passo Fundo, Passo Fundo, RS, 2020.http://tede.upf.br:8080/jspui/handle/tede/2045Methylphenidate (MPH) is a psychostimulant widely prescribed for the Treatment of Attention Deficit Hyperactivity Disorder (ADHD), since it decreases motor restlessness and promotes increased concentration, attention and memory. However, due to its stimulating effects, MPH has been used as an easily accessible drug of abuse, cognitive enhancer and can be added in dietary supplements, along with other stimulants, the most prevalent being caffeine (CAF). The effects of this irregular and abusive use of MPH are not yet fully understood. The main objective of this work was to evaluate the toxic effects of MPH, used acutely and in non-therapeutic doses, isolated or associated with CAF, through behavioral tests, oxidative stress markers and parameters of the mitochondrial respiratory chain, using zebrafish as an animal model. Fish were exposed for 15 minutes to 3 different doses: MPH 80 (80 mg / L), CAF 150 (150 mg / L) and MPH80 + CAF150 (80 mg / L + 150 mg / L). After exposure, exploratory behavior, social preference and memory were evaluated. The following mechanisms related to the observed changes were investigated: oxidative stress markers (lipid peroxidation, non-protein thiols, protein carbonylation), nitric oxide generation, protein level and energy status parameters (activity of mitochondrial complexes I, II-III and IV). We demonstrated that MPH used in an abusive way promotes antisocial behavior and induces protein carbonylation. Regarding the oxidative effects, isolated MPH had a protective effect, inhibiting lipid peroxidation. CAF used alone promotes an increase in the activities of the mitochondrial respiratory complexes (II-III and IV) and the generation of nitric oxide. The association of MPH and CAF in the non-therapeutic context promotes anxiogenic behavior and memory impairment. Although this association decreases lipid peroxidation, it promotes an increase in protein carbonylation, in addition to an increase in the activities of mitochondrial respiratory complexes (II-III and IV). Our results show that the nontherapeutic exposure of MPH and CAF has relevant effects on sociability and anxiety behavior. The association impairs memory. Mechanisms related to these changes are related to protein lesion, as evidenced by increases in protein carbonylation, as well as increases in mitochondrial metabolism.O metilfenidato (MTF) é um psicoestimulante amplamente prescrito para o Tratamento de Déficit de Atenção e Hiperatividade (TDAH), uma vez que diminui a inquietação motora e promove aumento da concentração, atenção e memória. Porém, devido aos seus efeitos estimulantes, o MTF vem sendo utilizado como droga de abuso de fácil acesso, potencializador cognitivo e pode ser encontrado em suplementos dietéticos de forma clandestina, juntamente com outros estimulantes, sendo o mais prevalente a cafeína (CAF). Os efeitos deste uso irregular e abusivo do MTF ainda não estão totalmente elucidados. O principal objetivo deste trabalho foi avaliar os efeitos tóxicos do MTF, utilizado de forma aguda e em doses não terapêuticas, isolado ou associado à CAF, através de ensaios comportamentais, marcadores de estresse oxidativo e parâmetros da cadeia respiratória mitocondrial, utilizando como modelo animal o zebrafish. Os peixes foram expostos durante 15 minutos a 3 diferentes doses: MTF 80 (80 mg/L), CAF 150 (150 mg/L) e MTF80+CAF150 (80 mg/L + 150 mg/L). Após a exposição, foram avaliados os comportamentos exploratório, preferência social e a memória. Foram investigados os seguintes mecanismos relacionados às alterações observadas: marcadores de estresse oxidativo (peroxidação lipídica, tióis não proteicos, carbonilação proteica), geração de óxido nítrico, nível de proteínas e parâmetros do status energético (atividade dos complexos mitocondriais I, II-III e IV). Neste estudo, nós demonstramos que o MTF utilizado de forma abusiva promove um comportamento antissocial e induz carbonilação de proteínas. Com relação aos efeitos oxidativos, o MTF isolado apresentou um efeito protetor, inibindo a peroxidação lipídica. A CAF utilizada isoladamente promove um aumento das atividades dos complexos respiratórios mitocondriais (II-III e IV) e da geração de óxido nítrico. A associação de MTF e CAF no contexto não terapêutico promove um comportamento ansiogênico e prejuízos de memória. Embora esta associação diminua a peroxidação lipídica, promove aumento na carbonilação proteica, além do aumento das atividades dos complexos respiratórios mitocondriais (II-III e IV). Nossos resultados evidenciam que a exposição não terapêutica do MTF e da CAF tem efeitos relevantes na sociabilização e no comportamento de ansiedade. A associação de MTF e CAF, frequentemente utilizados para melhorar o desempenho cognitivo, de acordo com nosso estudo, de fato, prejudica a memória. Os mecanismos associados aos efeitos observados com esta exposição envolvem lesão proteica, evidenciada pelo aumento da carbonilação proteica, bem como o aumento do metabolismo mitocondrial.Submitted by Jucelei Domingues (jucelei@upf.br) on 2021-05-31T19:52:19Z No. of bitstreams: 1 2020NataliaFreddo.pdf: 1162885 bytes, checksum: bb93216b27b20031fbba82b5f0456b97 (MD5)Made available in DSpace on 2021-05-31T19:52:20Z (GMT). No. of bitstreams: 1 2020NataliaFreddo.pdf: 1162885 bytes, checksum: bb93216b27b20031fbba82b5f0456b97 (MD5) Previous issue date: 2020-07-28Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPESFundação de Amparo à Pesquisa do Estado do Rio Grande do Sul - FAPERGSapplication/pdfporUniversidade de Passo FundoPrograma de Pós-Graduação em BioexperimentaçãoUPFBrasilFaculdade de Agronomia e Medicina Veterinária – FAMVMetilfenidatoCafeínaNeurofarmacologiaToxicologiaCIENCIAS AGRARIAS::MEDICINA VETERINARIAEfeitos tóxicos do uso abusivo de metilfenidato associado à cafeínaToxic effects of abusive use of methylphenidate associated with caffeineinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/masterThesis794520062517004959500500600600600532022005036727994536702642350173192075167498588264571-3614735573891122254info:eu-repo/semantics/openAccessreponame:Biblioteca de teses e dissertações da Universidade de Passo Fundo (BDTD UPF)instname:Universidade de Passo Fundo (UPF)instacron:UPFORIGINAL2020NataliaFreddo.pdf2020NataliaFreddo.pdfapplication/pdf1162885http://tede.upf.br:8080/jspui/bitstream/tede/2045/2/2020NataliaFreddo.pdfbb93216b27b20031fbba82b5f0456b97MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82053http://tede.upf.br:8080/jspui/bitstream/tede/2045/1/license.txt1ea0bfd7af108792edd8df732bb777fcMD51tede/20452021-05-31 16:52:20.098oai:tede.upf.br: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Biblioteca Digital de Teses e DissertaçõesPUBhttp://tede.upf.br/oai/requestbiblio@upf.br || bio@upf.br || cas@upf.br || car@upf.br || lve@upf.br || sar@upf.br || sol@upf.br || upfmundi@upf.br || jucelei@upf.bropendoar:2021-05-31T19:52:20Biblioteca de teses e dissertações da Universidade de Passo Fundo (BDTD UPF) - Universidade de Passo Fundo (UPF)false |
dc.title.por.fl_str_mv |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
dc.title.alternative.eng.fl_str_mv |
Toxic effects of abusive use of methylphenidate associated with caffeine |
title |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
spellingShingle |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína Freddo, Natália Metilfenidato Cafeína Neurofarmacologia Toxicologia CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
title_short |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
title_full |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
title_fullStr |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
title_full_unstemmed |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
title_sort |
Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína |
author |
Freddo, Natália |
author_facet |
Freddo, Natália |
author_role |
author |
dc.contributor.advisor1.fl_str_mv |
Grando, Luciana Grazziotin Rossato |
dc.contributor.advisor1ID.fl_str_mv |
00531009050 |
dc.contributor.advisor1Lattes.fl_str_mv |
http://lattes.cnpq.br/4915700374200518 |
dc.contributor.advisor-co1.fl_str_mv |
Barcellos, Leonardo José Gil |
dc.contributor.advisor-co1ID.fl_str_mv |
67458491000 |
dc.contributor.advisor-co1Lattes.fl_str_mv |
http://lattes.cnpq.br/4504482634911546 |
dc.contributor.authorID.fl_str_mv |
00475683056 |
dc.contributor.authorLattes.fl_str_mv |
http://lattes.cnpq.br/1475258536527110 |
dc.contributor.author.fl_str_mv |
Freddo, Natália |
contributor_str_mv |
Grando, Luciana Grazziotin Rossato Barcellos, Leonardo José Gil |
dc.subject.por.fl_str_mv |
Metilfenidato Cafeína Neurofarmacologia Toxicologia |
topic |
Metilfenidato Cafeína Neurofarmacologia Toxicologia CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
dc.subject.cnpq.fl_str_mv |
CIENCIAS AGRARIAS::MEDICINA VETERINARIA |
description |
Methylphenidate (MPH) is a psychostimulant widely prescribed for the Treatment of Attention Deficit Hyperactivity Disorder (ADHD), since it decreases motor restlessness and promotes increased concentration, attention and memory. However, due to its stimulating effects, MPH has been used as an easily accessible drug of abuse, cognitive enhancer and can be added in dietary supplements, along with other stimulants, the most prevalent being caffeine (CAF). The effects of this irregular and abusive use of MPH are not yet fully understood. The main objective of this work was to evaluate the toxic effects of MPH, used acutely and in non-therapeutic doses, isolated or associated with CAF, through behavioral tests, oxidative stress markers and parameters of the mitochondrial respiratory chain, using zebrafish as an animal model. Fish were exposed for 15 minutes to 3 different doses: MPH 80 (80 mg / L), CAF 150 (150 mg / L) and MPH80 + CAF150 (80 mg / L + 150 mg / L). After exposure, exploratory behavior, social preference and memory were evaluated. The following mechanisms related to the observed changes were investigated: oxidative stress markers (lipid peroxidation, non-protein thiols, protein carbonylation), nitric oxide generation, protein level and energy status parameters (activity of mitochondrial complexes I, II-III and IV). We demonstrated that MPH used in an abusive way promotes antisocial behavior and induces protein carbonylation. Regarding the oxidative effects, isolated MPH had a protective effect, inhibiting lipid peroxidation. CAF used alone promotes an increase in the activities of the mitochondrial respiratory complexes (II-III and IV) and the generation of nitric oxide. The association of MPH and CAF in the non-therapeutic context promotes anxiogenic behavior and memory impairment. Although this association decreases lipid peroxidation, it promotes an increase in protein carbonylation, in addition to an increase in the activities of mitochondrial respiratory complexes (II-III and IV). Our results show that the nontherapeutic exposure of MPH and CAF has relevant effects on sociability and anxiety behavior. The association impairs memory. Mechanisms related to these changes are related to protein lesion, as evidenced by increases in protein carbonylation, as well as increases in mitochondrial metabolism. |
publishDate |
2020 |
dc.date.issued.fl_str_mv |
2020-07-28 |
dc.date.accessioned.fl_str_mv |
2021-05-31T19:52:20Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/masterThesis |
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masterThesis |
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publishedVersion |
dc.identifier.citation.fl_str_mv |
FREDDO, Natália. Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína. 2020. 62 f. Dissertação (Mestrado em Bioexperimentação) - Universidade de Passo Fundo, Passo Fundo, RS, 2020. |
dc.identifier.uri.fl_str_mv |
http://tede.upf.br:8080/jspui/handle/tede/2045 |
identifier_str_mv |
FREDDO, Natália. Efeitos tóxicos do uso abusivo de metilfenidato associado à cafeína. 2020. 62 f. Dissertação (Mestrado em Bioexperimentação) - Universidade de Passo Fundo, Passo Fundo, RS, 2020. |
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http://tede.upf.br:8080/jspui/handle/tede/2045 |
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por |
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por |
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UPF |
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Brasil |
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Faculdade de Agronomia e Medicina Veterinária – FAMV |
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Universidade de Passo Fundo |
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