Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil; Department of Nutrition, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil.
Laboratório de Avaliações Farmacológicas e Toxicológicas Aplicadas às Moléculas Bioativas, LaftamBio Pampa, Universidade Federal do Pampa, Campus Itaqui, Rua Luiz Joaquim de Sá Britto, s/n - Bairro: Promorar, Itaqui, Rio Grande do Sul, CEP 97650-000, Brazil.
J Trace Elem Med Biol. 2019 Jul;54:232-243. doi: 10.1016/j.jtemb.2018.10.015. Epub 2018 Oct 15.
Neurodegeneration in Parkinson's disease appears to be caused by multiple factors, including oxidative damage and an increase in acetylcholinesterase expression that can culminate in loss of dopaminergic neurons. A selenium-containing quinoline derivative, 7-chloro-4-(phenylselanyl) quinoline (4-PSQ), shows important pharmacological actions mainly attributed to its antioxidant and anticholinesterase properties. Thus, this study investigated the neuroprotective effect of 4-PSQ in a model of Parkinson's-like disease induced by rotenone (ROT) in Drosophila melanogaster and verified whether these effects are related to selenium levels. Adult flies were divided into: [1] control, [2] 4-PSQ (25 μM), [3] ROT (500 μM), and [4] 4-PSQ (25 μM) + ROT (500 μM) groups and exposed to a diet containing ROT and/or 4-PSQ for 7 days, according to their respective groups. Survival, behavioral, and ex vivo analyses were performed. Dopamine levels, reactive species levels (RS), lipid peroxidation (LPO), superoxide dismutase (SOD) and catalase (CAT) activity, and proteic thiol (PSH) and non-proteic thiol (NPSH) content in the head region were analyzed, while acetylcholinesterase (AChE) activity and selenium levels in the head and body regions were analyzed. 4-PSQ was able to reverse the ROT-induced deficits in flies, reestablish dopamine and selenium levels, reverse cholinergic deficits, improve motor function, and ameliorate mortality. Furthermore, 4-PSQ also reduced RS levels and LPO, and restored the activities of the antioxidant enzymes, SOD and CAT. Interestingly, a positive relationship between dopamine and selenium levels could be seen. Our results demonstrate the neuroprotective effect of 4-PSQ, and we suggest that the compound may act via different mechanisms, such as improving antioxidant defenses and consequently reducing oxidative damages, as well as having an anticholinesterase action, which together can prevent dopamine depletion, as these actions were correlated with the presence of selenium in the 4-PSQ molecule.
帕金森病中的神经退行性变似乎是由多种因素引起的，包括氧化损伤和乙酰胆碱酯酶表达的增加，这最终可能导致多巴胺能神经元的丧失。一种含硒的喹啉衍生物，7-氯-4-（苯基硒基）喹啉（4-PSQ），具有重要的药理学作用，主要归因于其抗氧化和抗乙酰胆碱酯酶特性。因此，本研究在黑腹果蝇帕金森病样疾病模型中研究了 4-PSQ 的神经保护作用，并验证了这些作用是否与硒水平有关。成年果蝇分为：[1]对照组，[2]4-PSQ（25 μM）组，[3]ROT（500 μM）组和[4]4-PSQ（25 μM）+ ROT（500 μM）组，并根据各自的组别，在含有 ROT 和/或 4-PSQ 的饮食中暴露 7 天。进行了生存、行为和离体分析。分析了头部的多巴胺水平、活性物质水平（RS）、脂质过氧化（LPO）、超氧化物歧化酶（SOD）和过氧化氢酶（CAT）活性以及头部的蛋白巯基（PSH）和非蛋白巯基（NPSH）含量，同时分析了头部和身体区域的乙酰胆碱酯酶（AChE）活性和硒水平。4-PSQ 能够逆转 ROT 诱导的果蝇缺陷，重新建立多巴胺和硒水平，逆转胆碱能缺陷，改善运动功能，降低死亡率。此外，4-PSQ 还降低了 RS 水平和 LPO，并恢复了抗氧化酶 SOD 和 CAT 的活性。有趣的是，多巴胺和硒水平之间存在正相关关系。我们的结果表明 4-PSQ 具有神经保护作用，我们认为该化合物可能通过不同的机制发挥作用，例如改善抗氧化防御，从而减少氧化损伤，以及具有抗乙酰胆碱酯酶作用，这两者都可以防止多巴胺耗竭，因为这些作用与 4-PSQ 分子中的硒有关。
