Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090 Lublin, Poland.
Chair and Department of Toxicology, Faculty of Pharmacy, Medical University of Lublin, Jaczewskiego 8b Street, 20-090 Lublin, Poland.
Toxicol Appl Pharmacol. 2019 Oct 1;380:114689. doi: 10.1016/j.taap.2019.114689. Epub 2019 Jul 22.
Chronic exposure to environmental-like stress leads to dysregulation of hypothalamic-pituitary-adrenal (HPA) axis and to appearance of oxidative stress, which is implicated in the development of depression-like behaviour. Edaravone (3-methyl-1-phenyl-2-pyrazoline-5-one) exhibits a neuroprotective effect attributed to the potent free radical scavenging. This study was designed to assess antidepressant-like activity of edaravone based on behavioural tests in the animal model of depression. Furthermore, to elucidate its mechanisms, the expression of Fkbp5, Comt, Adora and Slc6a15 genes involved in turnover of neurotransmitters was analysed. In order to evaluate the antioxidant features of edaravone, DNA's oxidative damage was determined. The mice were injected subcutaneously (sc) with 40 mg/kg corticosterone, chronically for 21 days. Paroxetine (10 mg/kg) (a selective serotonin reuptake inhibitor) and edaravone (10 mg/kg) were administered separately (ip) 30 min prior to the corticosterone injection. After 21-days of treatment with respective drugs, the mice were decapitated and the prefrontal cortex was rapidly dissected and used for determination of DNA's oxidative damage and the real-time PCR analysis. Edaravone ameliorated behavioural impairments in sucrose preference test (SPT) and forced swim test (FST). A possible role in Fkbp5, Comt, Adora1 and Slc6a15 genes' expression in mediating this effect is postulated. Both edaravone and paroxetine have no effect on corticosterone-induced DNA's oxidative damage.
慢性暴露于类似环境的应激会导致下丘脑-垂体-肾上腺（HPA）轴失调和氧化应激的出现，这与抑郁样行为的发展有关。依达拉奉（3-甲基-1-苯基-2-吡唑啉-5-酮）表现出神经保护作用，归因于其强大的自由基清除能力。本研究旨在评估依达拉奉基于抑郁动物模型的行为测试的抗抑郁样活性。此外，为了阐明其机制，分析了涉及神经递质代谢的 Fkbp5、Comt、Adora 和 Slc6a15 基因的表达。为了评估依达拉奉的抗氧化特性，测定了 DNA 的氧化损伤。将小鼠皮下（sc）注射 40mg/kg 地塞米松，慢性注射 21 天。帕罗西汀（10mg/kg）（一种选择性 5-羟色胺再摄取抑制剂）和依达拉奉（10mg/kg）分别（ip）在皮质酮注射前 30 分钟给药。用相应药物治疗 21 天后，将小鼠断头，迅速取出前额叶皮质，用于测定 DNA 的氧化损伤和实时 PCR 分析。依达拉奉改善了蔗糖偏好测试（SPT）和强迫游泳测试（FST）中的行为损伤。推测 Fkbp5、Comt、Adora1 和 Slc6a15 基因表达在介导这种作用中可能起作用。依达拉奉和帕罗西汀对皮质酮诱导的 DNA 氧化损伤均无影响。
