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Mitochondrial Cumulative Damage Induced by Mitoxantrone: Late Onset Cardiac Ene...

Rossato, Luciana Grazziotin; Costa, Vera Marisa; Dallegrave, Eliane; Arbo, Marcelo; Silva, Renata; Ferreira, Rita; Amado, Francisco

Mitoxantrone (MTX) is a chemotherapeutic agent, which presents late irreversible cardiotoxicity. This work aims to highlight the mechanisms involved in the MTX-induced cardiotoxicity, namely the effects toward mitochondria using in vivo and in vitro studies. Male Wistar rats were treated with 3 cycles of 2.5 mg/kg MTX at day 0, 10, and 20. One treated group was euthanized on day 22 (MTX22) to evaluate the early...


Therapeutic Concentrations of Mitoxantrone Elicit Energetic Imbalance in H9c2 C...

Rossato, Luciana Grazziotin; Costa, Vera Marisa; Vilas-Boas, Vânia; Bastos, Maria de Lourdes; Rolo, Anabela; Palmeira, C. M.; Remião, Fernando

Mitoxantrone (MTX) is a chemotherapeutic agent that emerged as an alternative to anthracycline therapy. However, MTX also causes late cardiotoxicity, being oxidative stress and mitochondrial-impaired function proposed as possible mechanisms. This work aimed to investigate the relevance of these mechanisms to the MTX toxicity in H9c2 cells, using therapeutic concentrations. The observed cytotoxicity of MTX was t...


The metabolic profile of mitoxantrone and its relation with mitoxantrone-induce...

Rossato, Luciana Grazziotin; Costa, Vera Marisa; de Pinho, Paula Guedes; Arbo, Marcelo Dutra; de Freitas, Vitor; Vilain, Laure; Bastos, Maria de Lourdes

Mitoxantrone (MTX) is an antitumor agent that causes cardiotoxicity in 18 % patients. The metabolic profile of MTX was assessed after incubation of 100 lM MTX with hepatic S9 fraction isolated from rats. The presence of MTX and its metabolites was also assessed in vivo through the analysis of liver and heart extracts of MTX-treated rats. The cytotoxic effects of MTX and MTX metabolites were evaluated in the H9c...


Role of catecholamines and reactive oxygen species in the mechanism of oxidativ...

Costa, Vera Marisa Freitas

Doutoramento em Toxicologia ; PhD Degree - Toxicology


Cross-Functioning between the Extraneuronal Monoamine Transporter and Multidrug...

Costa, Vera Marisa; Ferreira, Luísa Maria; Branco, Paula Sério; Carvalho, Félix; Bastos, Maria Lourdes; Carvalho, Rui Albuquerque; Carvalho, Márcia

Isolated heart cells are highly susceptible to the toxicity of catecholamine oxidation products, namely, to catecholamine-glutathione adducts. Although cellular uptake and/or efflux of these products may constitute a crucial step, the knowledge about the involvement of transporters is still very scarce. This work aimed to contribute to the characterization of membrane transport mechanisms, namely, extraneuronal...


Time dependent activation of transcription factors in freshly isolated cardiomy...

Costa, Vera Marisa; Carvalho, Felix; Bastos, Maria de Lourdes; Carvalho, Rui; Carvalho, Márcia; Remião, Fernando

http://www.sciencedirect.com/science/article/B6TCR-4PKH640-H/1/d0195093d7c07e99f21ac2b29efae75f


Oxidation Process of Adrenaline in Freshly Isolated Rat Cardiomyocytes: Formati...

Costa, Vera Marisa; Silva, Renata; Ferreira, Luísa Maria; Branco, Paula Sério; Carvalho, Félix; Bastos, Maria Lourdes; Carvalho, Rui Albuquerque

High concentrations of circulating biogenic catecholamines often exist during the course of several cardiovascular disorders. Additionally, coronary dysfunctions are prominent and frequently related to the ischemic and reperfusion phenomenon (I/R) in the heart, which leads to the release of large amounts of catecholamines, namely adrenaline, and to a sustained generation of reactive oxygen species (ROS). Thus, ...


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    Financiadores do RCAAP

Fundação para a Ciência e a Tecnologia Universidade do Minho   Governo Português Ministério da Educação e Ciência Programa Operacional da Sociedade do Conhecimento União Europeia