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Neurotoxicity of heroin-cocaine combinations in rat cortical neurons

Cunha-Oliveira, Teresa; Rego, A Cristina; Garrido, Jorge; Borges, Fernanda; Macedo, Tice; Oliveira, Catarina R

Cocaine and heroin are frequently co-abused by humans, in a combination known as speedball. Recently, chemical interactions between heroin (Her) or its metabolite morphine (Mor) and cocaine (Coc) were described, resulting in the formation of strong adducts. In this work, we evaluated whether combinations of Coc and Her affect the neurotoxicity of these drugs, using rat cortical neurons incubated with Coc, Her, ...


Drugs of abuse induce apoptotic features in PC12 cells.

Oliveira, M Teresa; Rego, A Cristina; Macedo, Tice R; Oliveira, Catarina R

Drugs of abuse induce the release of dopamine in the central nervous system, particularly in the mesolimbic-mesocortical pathway. As dopamine may act as a neurotoxin, in this study, we analyzed the effects of the drugs of abuse, cocaine, heroin, and amphetamine, on the neurodegeneration of PC12 cells, a dopaminergic cell line, by evaluating the activity of caspase-3 and mitochondrial cytochrome c release. All t...


Toxic Effects of Opioid and Stimulant Drugs on Undifferentiated PC12 Cells

Oliveira, M Teresa; Rego, A Cristina; Morgadinho, M Teresa; Macedo, Tice R; Oliveira, Catarina R

Cell death and reactive oxygen species production have been suggested to be involved in neurodegeneration induced by the drugs of abuse. In this study we analyze the toxicity of the following drugs of abuse: heroin, morphine, d-amphetamine, and cocaine in undifferentiated PC12 cells, used as dopaminergic neuronal models. Our data show that opioid drugs (heroin and morphine) are more toxic than stimulant drugs (...


Expression of NR1/NR2B N-Methyl-d-Aspartate Receptors Enhances Heroin Toxicity ...

Domingues, António; Cunha-Oliveira, Teresa; Laço, Mário LN; Macedo, Tice; Oliveira, Catarina R; Rego, A Cristina

Repeated use of drugs of abuse, namely opiates, has been shown to affect glutamate-releasing neurons. Moreover, blockade of N-methyl-D-aspartate (NMDA) receptors (NMDAR) prevents cell death by apoptosis induced by morphine, a heroin metabolite. Thus, in this article we investigated the involvement of different NMDAR subunits in heroin cytotoxicity. Human embryonic kidney (HEK293)cells, which do not express nati...


Efeito crónico da heroína e do peróxido de hidrogénio em células PC12

Cunha-Oliveira, Teresa; Rego, A Cristina; Morgadinho, M Teresa; Macedo, Tice R; Oliveira, Catarina R

O consumo repetido de drogas, nomeadamente opióides, conduz ao desenvolvimento de dependência. Entre os mecanismos envolvidos neste processo, comuns à maioria das drogas de abuso, destaca-se a activação da neurotransmissão dopaminérgica em zonas específicas do cérebro. O metabolismo oxidativo da dopamina confere-lhe um potencial neurotóxico devido à formação de espécies reactivas de oxigénio, nomeadamente peróx...


Controvérsias na Anticoagulação Oral: Continuar ou Interromper os Anticoagulant...

António, Natália; Castro, Graça; Ramos, Domingo; Machado, António; Gonçalves, Lino; Macedo, Tice; Providência, Luís A.

A abordagem dos doentes cronicamente anticoagulados com necessidade de intervenções estomatológicas continua a suscitar grande controvérsia. O aumento do risco hemorrágico associado aos procedimentos estomatológicos sob anticoagulação oral deve ser pesado relativamente ao risco trombótico acrescido causado pela interrupção da terapêutica antitrombótica. Em cirurgia oral minor, a mortalidade e morbilidade é supe...


Street heroin induces mitochondrial dysfunction and apoptosis in rat cortical n...

Cunha-Oliveira, Teresa; Rego, A. Cristina; Garrido, Jorge; Borges, Fernanda; Macedo, Tice; Oliveira, Catarina Resende

Cortical function has been suggested to be highly compromised by repeated heroin self-administration. We have previously shown that street heroin induces apoptosis in neuronal-like PC12 cells. Thus, we analysed the apoptotic pathways involved in street heroin neurotoxicity using primary cultures of rat cortical neurons. Our street heroin sample was shown to be mainly composed by heroin, 6-monoacetylmorphine and...


Unaltered hepatic oxidative phosphorylation and mitochondrial permeability tran...

Moreno, António J.; Oliveira, Paulo J.; Nova, Carlos D.; Álvaro, Ana R.; Moreira, Renata A.; Santos, Sandra M. D.; Macedo, Tice

Nonsteroidal anti-inflammatory drugs have been associated with hepatotoxicity in susceptible patients. One such example is nimesulide, a preferential cyclooxygenase 2-inhibitor, widely used for the treatment of inflammation and pain. It was suggested that nimesulide could exert its hepatotoxicity by altering hepatic mitochondrial function, which was demonstrated in vitro. The objective of this study was to veri...


Spectroscopic and electrochemical studies of cocaine–opioid interactions

Garrido, Jorge; Marques, M.; Silva, Artur; Macedo, Tice; Oliveira-Brett, Ana; Borges, Fernanda

Abstract The drugs of abuse cocaine (C), heroin (H), and morphine (M) have been studied to enable understanding of the occurrence of cocaine–opioid interactions at a molecular level. Electrochemical, Raman, and NMR studies of the free drugs and their mixtures were used to study drug–drug interactions. The results were analyzed using data obtained from quantum-mechanical calculations. For the cocaine–morphine m...


Differential cytotoxic responses of PC12 cells chronically exposed to psychosti...

Cunha-Oliveira, Teresa; Rego, A. Cristina; Morgadinho, Maria Teresa; Macedo, Tice; Oliveira, Catarina Resende

Repeated abuse of stimulant drugs, cocaine and amphetamine, is associated with extraneuronal dopamine accumulation in specific brain areas. Dopamine may be cytotoxic through the generation of reactive oxygen species, namely hydrogen peroxide (H2O2), resulting from dopamine oxidative metabolism. In this work, we studied the cytotoxicity in PC12 cells (a dopaminergic neuronal model) chronically and/or acutely exp...


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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