Cocaine is one of the most popular illicit drug worldwide. Due its great addictive potential, which leads to euphoria and hyperactivity, it is considered a public health concern. At the central nervous system, the drug acts inhibiting catecholamine re-uptake. It is now known that in addition to the toxicity of the drug itself, the contaminants present in the street drug have raised concern about the harmful effects on health. Toxicological in vivo and in vitro studies have demonstrated the toxic effects of cocaine correlated with the generation of reactive oxygen species (ROS), which in turn lead to oxidative damage to the cells. Therefore the aim of this work was to propose an in vitro model that reunites the main parameters of toxicity of the cocaine already observed in the literature so far, and we tested this model using cocaine and seizure cocaine sample (SCS), kindly provided by Federal Police of Brazil. For that, we used a C6 glioblastoma cells and evaluated cell death, oxygen reactive species induction, oxidation of macromolecules as membrane lipids and DNA and loss of mitochondrial membrane potential after cocaine exposure. The results showed that cocaine can decrease cellular viability in a dose-dependent way in the C6 cell immortalized and astrocytes primary culture. Cocaine also induced cellular death by apoptosis. However, in the seizure cocaine sample (SCS), the predominant cell death was due to necrosis. Using dichlorofluorescein (DCF) assay, we confirmed ROS production after cocaine exposition. In agreement with these findings, occurred an increasing in MDA production, as well as increased superoxide dismutase (SOD) and catalase (CAT) activity. The induction of DNA damage was observed after cocaine. Our results demonstrate the occurrence of mitochondrial dysfunction by depolarization of mitochondrial membrane as a consequence of cocaine treatment. In summary, these results demonstrated that cocaine can induce reactive oxygen species formation, leading to oxidative stress. As a consequence of this unbalance, DNA damage, lipidic peroxidation and loss of mitochondrial membrane occurred, which could be an answer to cell death observed.

可卡因是全球最受欢迎的非法药物之一。由于其巨大的成瘾潜力，会导致欣快和过度活跃，因此被认为是公共健康问题。在中枢神经系统，该药物具有抑制儿茶酚胺再摄取的作用。现已知道，除了药物本身的毒性外，街头毒品中存在的污染物也引起了人们对健康的有害影响。体内和体外毒理学研究表明，可卡因的毒性作用与活性氧（ROS）的产生有关，而活性氧又导致细胞的氧化损伤。因此，这项工作的目的是提出一种体外该模型重新组合了迄今为止在文献中已经观察到的可卡因毒性的主要参数，并且我们使用可卡因和缉获的可卡因样品（SCS）（由巴西联邦警察提供）对该模型进行了测试。为此，我们使用了C6胶质母细胞瘤细胞并评估了细胞死亡，氧反应性物种的诱导，大分子作为膜脂质和DNA的氧化以及可卡因暴露后线粒体膜电位的损失。结果表明，可卡因可以在永生的C6细胞和星形胶质细胞的原代培养中以剂量依赖的方式降低细胞活力。可卡因还通过凋亡诱导细胞死亡。然而，在癫痫发作的可卡因样本（SCS）中，主要的细胞死亡是由于坏死引起的。使用二氯荧光素（DCF）分析，我们确认了可卡因暴露后ROS的产生。与这些发现一致，MDA产生增加，超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性增加。可卡因后观察到DNA损伤的诱导。我们的研究结果表明，可卡因治疗可导致线粒体膜去极化，从而导致线粒体功能障碍。总之，这些结果表明可卡因可以诱导活性氧的形成，从而导致氧化应激。这种不平衡的结果是发生了DNA损伤，脂质过氧化和线粒体膜丢失，这可能是观察到的细胞死亡的答案。我们的研究结果表明，可卡因治疗可导致线粒体膜去极化，从而导致线粒体功能障碍。总之，这些结果表明可卡因可以诱导活性氧的形成，从而导致氧化应激。这种不平衡的结果是发生了DNA损伤，脂质过氧化和线粒体膜丢失，这可能是观察到的细胞死亡的答案。我们的研究结果表明，可卡因治疗可导致线粒体膜去极化，从而导致线粒体功能障碍。总之，这些结果表明可卡因可以诱导活性氧的形成，从而导致氧化应激。这种不平衡的结果是发生了DNA损伤，脂质过氧化和线粒体膜丢失，这可能是观察到的细胞死亡的答案。