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Oxidative Stress and Drugs of Abuse: An Update
Cunha-Oliveira, Teresa; Rego, A. Cristina; Oliveira, Catarina R.Drug addiction is a public health and social burden. Presently, the most abused illicit substance is cannabis, followed by amphetamines, cocaine and opioids, with different prevalence in different countries. Several evidences support a role for oxidative stress in the toxicity induced by many drugs of abuse in different organs, such as the brain, heart, liver or kidneys. This leads to oxidation of important cel...
Mitochondrial complex I dysfunction induced by cocaine and cocaine plus morphin...
Cunha-Oliveira, Teresa; Silva, Lisbeth; Silva, Ana Maria; Moreno, António J.; Oliveira, Catarina R.; Santos, Maria S.Mitochondrial function and energy metabolism are affected in brains of human cocaine abusers. Cocaine is known to induce mitochondrial dysfunction in cardiac and hepatic tissues, but its effects on brain bioenergetics are less documented. Furthermore, the combination of cocaine and opioids (speedball) was also shown to induce mitochondrial dysfunction. In this work, we compared the effects of cocaine and/or mor...
Dimethylaminopyridine derivatives of lupane triterpenoids cause mitochondrial d...
Bernardo, Telma C.; Cunha-Oliveira, Teresa; Serafim, Teresa L.; Holy, Jon; Krasutsky, Dmytro; Kolomitsyna, Oksana; Krasutsky, Pavel; Moreno, A. J. M.Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as anticancer agents have been found to target mitochondria. The objective of the present work was to investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP) derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma cells in vit...
Neurotoxicity of heroin-cocaine combinations in rat cortical neurons
Cunha-Oliveira, Teresa; Rego, A Cristina; Garrido, Jorge; Borges, Fernanda; Macedo, Tice; Oliveira, Catarina RCocaine 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, ...
Consequences of mitochondrial dysfunction in Huntington's Disease and protectio...
Cunha-Oliveira, Teresa; Ferreira, Ildete L; Rego, A CristinaHuntington’s Disease (HD) is an autosomal dominant neurodegenerative disorder clinically characterized by psychiatric disturbances, progressive cognitive impairment and choreiform movements. These symptoms are associated with the selective atrophy and neuronal loss in the striatum, cortex and hypothalamus. The disease is caused by a mutation at the 5’ terminal of the huntingtin (HTT) gene involving the expansio...
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 CristinaRepeated 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 RO 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...
Revisiting oxidative stress and mitochondrial dysfunction in the pathogenesis o...
Perfeito, Rita; Cunha-Oliveira, Teresa; Rego, Ana CristinaParkinson disease (PD) is a chronic and progressive neurological disease associated with a loss of dopaminergic neurons. In most cases the disease is sporadic but genetically inherited cases also exist. One of the major pathological features of PD is the presence of aggregates that localize in neuronal cytoplasm as Lewy bodies, mainly composed of α-synuclein (α-syn) and ubiquitin. The selective degeneration of ...
Glutathione redox cycle dysregulation in Huntington’s disease knock-in striatal...
Ribeiro, Márcio; Rosenstock, Tatiana; Cunha-Oliveira, Teresa; Ferreira, Ildete; Oliveira, Catarina R.; Rego, Ana CristinaHuntington’s disease (HD) is a CAG repeat disorder affecting the HD gene, which encodes for huntingtin (Htt) and is characterized by prominent cell death in the striatum. Oxidative stress was previously implicated in HD neurodegeneration, but the role of the major endogenous antioxidant system, the glutathione redox cycle, has been less studied following expression of full-length mutant Htt (FL-mHtt). Thus, in ...
Cellular and molecular mechanisms involved in the neurotoxicity of opioid and p...
Cunha-Oliveira, Teresa; Rego, Ana Cristina; Oliveira, Catarina R.Substance abuse and addiction are the most costly of all the neuropsychiatric disorders. In the last decades, much progress has been achieved in understanding the effects of the drugs of abuse in the brain. However, efficient treatments that prevent relapse have not been developed. Drug addiction is now considered a brain disease, because the abuse of drugs affects several brain functions. Neurological impairme...
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