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Avaliação in vitro da nefrotoxicidade de catinonas sintéticas
| Name: | Description: | Size: | Format: | |
|---|---|---|---|---|
| PPG_27514 | 2.13 MB | Adobe PDF |
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Abstract(s)
O mundo das drogas recreativas alterou-se nas últimas décadas com o aparecimento contínuo de novas substâncias psicoativas (NSP), sendo a população jovem a mais afetada por estas substâncias. Entre estas NSP destacam-se as catinonas sintéticas que são química e estruturalmente semelhantes às anfetaminas, sendo também denominadas de “β-ceto anfetaminas”, apresentando propriedades psicostimulantes. Embora atualmente muitas destas novas drogas já sejam ilegais em muitos países, estas drogas apareceram inicialmente no mercado como alternativas legais ("drogas legais") a drogas ilícitas bem conhecidas, tais como as anfetaminas e a cocaína. Nos últimos anos foram descritos vários casos de intoxicações e mortes associadas ao consumo destas drogas. Desta forma, é de grande importância a realização de estudos que avaliem o seu potencial tóxico e o risco para a saúde dos seus consumidores. Neste trabalho pretendeu-se avaliar os potenciais efeitos nefrotóxicos de cinco derivados sintéticos da catinona comumente consumidos, nomeadamente a 3,4-metilenodioxipirovalerona (MDPV), metilona, pentedrona, 3,4-dimetilmetcatinona (3,4-DMMC) e 4-metiletcatinona (4-MEC), usando a linha celular HK-2 como modelo in vitro. As células HK-2 foram expostas a uma ampla gama de concentrações, de 0,01 a 3 mM para a 3,4-DMMC e de 0,1 a 10 mM para as restantes catinonas sintéticas estudadas, durante 24 e 48 horas. A toxicidade foi avaliada usando o ensaio de redução do MTT que permite estimar a viabilidade celular. Os resultados obtidos nesta dissertação mostraram pela primeira vez que as β-ceto-anfetaminas estudadas induziram nefrotoxicidade, pelo menos no modelo in vitro usado, de modo dependente da concentração e do tempo de exposição. A 3,4-DMMC foi o derivado da catinona que exibiu maior toxicidade para as células HK-2, seguida da MDPV, pentedrona, metilona, e, por último, a 4-MEC. Contudo, são necessários estudos adicionais para a compreensão dos mecanismos subjacentes aos efeitos nefrotóxicos das β-ceto-anfetaminas.
The world of recreational drugs has changed in the last decades with the continuous appearance of new psychoactive substances (NPS), being the young population the most affected by these substances. Among these NPS are synthetic cathinones that are chemically and structurally similar to amphetamines, being also called “β-keto amphetamines”, possessing psychostimulant properties. Although many of these new drugs are now illegal in many countries, these drugs have initially appeared on the market as legal alternatives ("legal drugs") to well-known illicit drugs such as amphetamines and cocaine. Some cases of intoxication and death related to these drugs consumption have been reported in the last few years. Thus, it is really important to carry out studies that assess their toxic potential and health risks to consumers. The purpose of this study was to evaluate the potential nephrotoxic effects of five commonly used cathinone synthetic derivatives, namely 3,4-methylenedioxypyrovalerone (MDPV), methylone, pentedrone, 3,4-dimethylmetcatinone (3,4-DMMC) and 4-methylethcatinone (4-MEC) using the HK-2 cell line as an in vitro model. The HK-2 cells were exposed to a wide range of concentrations, specifically 0.01-3 mM for 3,4-DMMC and 0.1-10 mM for all the others synthetic cathinones, for 24 and 48 hours. The toxicity assessment was performed using the MTT reduction assay for evaluating cell viability. The results obtained in the present study showed for the first time that the tested β-keto amphetamines induced nephrotoxicity, at least in this in vitro model, in a concentration- and time-dependent manner. 3,4-DMMC was found to be the cathinone derivative that exhibited the highest toxicity for HK-2 cells, followed by MDPV, pentedrone, methylone, and 4-MEC. However, further studies are needed to understand the mechanisms underlying the nephrotoxic effects of β-keto-amphetamines.
The world of recreational drugs has changed in the last decades with the continuous appearance of new psychoactive substances (NPS), being the young population the most affected by these substances. Among these NPS are synthetic cathinones that are chemically and structurally similar to amphetamines, being also called “β-keto amphetamines”, possessing psychostimulant properties. Although many of these new drugs are now illegal in many countries, these drugs have initially appeared on the market as legal alternatives ("legal drugs") to well-known illicit drugs such as amphetamines and cocaine. Some cases of intoxication and death related to these drugs consumption have been reported in the last few years. Thus, it is really important to carry out studies that assess their toxic potential and health risks to consumers. The purpose of this study was to evaluate the potential nephrotoxic effects of five commonly used cathinone synthetic derivatives, namely 3,4-methylenedioxypyrovalerone (MDPV), methylone, pentedrone, 3,4-dimethylmetcatinone (3,4-DMMC) and 4-methylethcatinone (4-MEC) using the HK-2 cell line as an in vitro model. The HK-2 cells were exposed to a wide range of concentrations, specifically 0.01-3 mM for 3,4-DMMC and 0.1-10 mM for all the others synthetic cathinones, for 24 and 48 hours. The toxicity assessment was performed using the MTT reduction assay for evaluating cell viability. The results obtained in the present study showed for the first time that the tested β-keto amphetamines induced nephrotoxicity, at least in this in vitro model, in a concentration- and time-dependent manner. 3,4-DMMC was found to be the cathinone derivative that exhibited the highest toxicity for HK-2 cells, followed by MDPV, pentedrone, methylone, and 4-MEC. However, further studies are needed to understand the mechanisms underlying the nephrotoxic effects of β-keto-amphetamines.
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Keywords
Catinonas sintéticas Drogas legais Sais de banho Nefrotoxicidade Células HK-2 Viabilidade celular Synthetic cathinones Legal highs Bath salts Nephrotoxicity HK-2 cells Cell viability