A carregar...
Publicação
Papel do stress oxidativo na cardiotoxicidade da 3,4-dimetilmetcatinona: estudo in vitro em células H9c2
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| Projeto de pós-graduação_41143 | 1.68 MB | Adobe PDF |
Orientador(es)
Resumo(s)
As catinonas sintéticas fazem parte do grupo das novas substâncias psicoativas (NSP) e são amplamente utilizadas como drogas recreativas devido aos seus efeitos psicoestimulantes, semelhantes aos das anfetaminas. A sua rápida disseminação constitui uma preocupação crescente para a saúde pública, sobretudo pelo risco de efeitos cardiovasculares graves, como arritmias, enfarte agudo do miocárdio e insuficiência cardíaca. Contudo, os mecanismos subjacentes à sua cardiotoxicidade permanecem pouco esclarecidos. Este estudo teve como objetivo investigar o potencial efeito cardiotóxico de uma destas substâncias, a 3,4-dimetilmetcatinona (3,4-DMMC), bem como o envolvimento do stress oxidativo neste processo. As células H9c2 foram expostas a várias concentrações de 3,4-DMMC (0,005 a 0,8 mM) durante 24 e 48 horas. A viabilidade celular foi avaliada através do ensaio de redução do MTT. A produção de espécies reativas de oxigénio e azoto (ROS/RNS) foi medida por fluorescência, utilizando o marcador DCFH-DA, em diferentes tempos (0,5 a 48 h), após incubação com a 3,4-DMMC nas concentrações correspondentes à EC10 e EC50. Para avaliar o efeito protetor de antioxidantes, as células foram pré-incubadas com ácido ascórbico (AA, 0,1 mM), Nacetilcisteína (NAC, 1 mM) ou Trolox (TRX, 0,2 mM), seguidas de exposição à 3,4- DMMC na concentração equivalente à EC40 durante 24 e 48 horas. A 3,4-DMMC reduziu significativamente a viabilidade celular de forma dependente da concentração, sem diferenças estatisticamente significativas entre os dois tempos de incubação. Observou-se um aumento progressivo dos níveis de ROS/RNS ao longo do tempo, com significância estatística a partir das 3 horas. Entre os antioxidantes testados, apenas o ácido ascórbico conseguiu atenuar os efeitos tóxicos da 3,4-DMMC. Os resultados obtidos demonstram que a 3,4-DMMC induz cardiotoxicidade in vitro de forma dependente da concentração, estando o stress oxidativo envolvido neste efeito. O ácido ascórbico revelou um efeito protetor claro, reforçando a importância de estudos futuros para melhor compreender os mecanismos de toxicidade e identificar estratégias terapêuticas eficazes.
Synthetic cathinones are part of the group of new psychoactive substances (NPS) and are widely used as recreational drugs due to their psychostimulant effects, similar to amphetamines. Their rapid emergence poses a growing public health concern, primarily due to their potential to cause serious cardiovascular effects such as arrhythmias, acute myocardial infarction, and heart failure. However, the underlying mechanisms of their cardiotoxicity remain poorly understood. This study aimed to investigate the potential cardiotoxic effects of one such compound, 3,4-dimethylmethcathinone (3,4-DMMC), and to explore the involvement of oxidative stress in this process. H9c2 cardiomyoblast cells were exposed to varying concentrations of 3,4-DMMC (0.005 to 0.8 mM) for 24 and 48 hours. Cell viability was assessed using the MTT reduction assay. Reactive oxygen and nitrogen species (ROS/RNS) production was measured via fluorescence using the DCFHDA probe at multiple time points (0.5 to 48h) following exposure to the EC10 and EC50 concentrations of 3,4-DMMC. To evaluate the potential protective effect of antioxidants, cells were pre-treated with ascorbic acid (AA, 0.1 mM), N-acetylcysteine (NAC, 1 mM), or Trolox (TRX, 0.2 mM) prior to exposure to 3,4-DMMC at its EC40 concentration for 24 and 48 hours. 3,4-DMMC significantly decreased cell viability in a concentrationdependent manner, with no significant differences observed between the two exposure durations. A time-dependent increase in ROS/RNS levels was detected, reaching statistical significance from 3 hours onward. Among the antioxidants tested, only ascorbic acid effectively mitigated the toxic effects of 3,4-DMMC. The findings demonstrate that 3,4-DMMC induces concentration-dependent cardiotoxicity in vitro, with oxidative stress being at least one of the contributing mechanisms. Ascorbic acid showed a clear protective effect, highlighting the relevance of further studies to elucidate the toxic pathways involved and explore potential therapeutic strategies.
Synthetic cathinones are part of the group of new psychoactive substances (NPS) and are widely used as recreational drugs due to their psychostimulant effects, similar to amphetamines. Their rapid emergence poses a growing public health concern, primarily due to their potential to cause serious cardiovascular effects such as arrhythmias, acute myocardial infarction, and heart failure. However, the underlying mechanisms of their cardiotoxicity remain poorly understood. This study aimed to investigate the potential cardiotoxic effects of one such compound, 3,4-dimethylmethcathinone (3,4-DMMC), and to explore the involvement of oxidative stress in this process. H9c2 cardiomyoblast cells were exposed to varying concentrations of 3,4-DMMC (0.005 to 0.8 mM) for 24 and 48 hours. Cell viability was assessed using the MTT reduction assay. Reactive oxygen and nitrogen species (ROS/RNS) production was measured via fluorescence using the DCFHDA probe at multiple time points (0.5 to 48h) following exposure to the EC10 and EC50 concentrations of 3,4-DMMC. To evaluate the potential protective effect of antioxidants, cells were pre-treated with ascorbic acid (AA, 0.1 mM), N-acetylcysteine (NAC, 1 mM), or Trolox (TRX, 0.2 mM) prior to exposure to 3,4-DMMC at its EC40 concentration for 24 and 48 hours. 3,4-DMMC significantly decreased cell viability in a concentrationdependent manner, with no significant differences observed between the two exposure durations. A time-dependent increase in ROS/RNS levels was detected, reaching statistical significance from 3 hours onward. Among the antioxidants tested, only ascorbic acid effectively mitigated the toxic effects of 3,4-DMMC. The findings demonstrate that 3,4-DMMC induces concentration-dependent cardiotoxicity in vitro, with oxidative stress being at least one of the contributing mechanisms. Ascorbic acid showed a clear protective effect, highlighting the relevance of further studies to elucidate the toxic pathways involved and explore potential therapeutic strategies.
Descrição
Palavras-chave
Catinonas sintéticas Cardiotoxicidade Stress oxidativo Antioxidantes Synthetic cathinones Cardiotoxicity Oxidative stress Antioxidants 3,4-DMMC