Programa de Pós-graduação em Bioquímica e Bioprospecção, Laboratório de Pesquisa em Farmacologia Bioquímica (LaFarBio), Grupo de Pesquisa em Neurobiotecnologia (GPN), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), CEP 96010-900, Pelotas, RS, Brazil.
Programa de Pós-graduação em Química, Laboratório de Síntese Orgânica Limpa - (LASOL), Centro de Ciências Químicas, Farmacêuticas e de Alimentos, Universidade Federal de Pelotas (UFPel), P.O. Box 354, Pelotas, RS, 96010-900, Brazil.
Metab Brain Dis. 2020 Apr;35(4):589-600. doi: 10.1007/s11011-020-00535-0. Epub 2020 Feb 12.
The present study evaluated the anti-amnesic activity of 1-(7-chloroquinolin-4-yl)-5-methyl-N-phenyl-1H-1,2,3-triazole-4-carboxamide (QTCA-1) against scopolamine (SCO)-induced amnesia in mice. It was evaluated cholinergic dysfunction, oxidative stress and Na/K-ATPase activity in cerebral cortex and hippocampus of mice. Male Swiss mice were treated with QTCA-1 (10 mg/kg, intragastrically (i.g.), daily) for nine days. Thirty minutes after the treatment with compound, the animals received a injection of SCO (0.4 mg/kg, intraperitoneally (i.p.)). Mice were submitted to the behavioral tasks 30 min after injection of SCO (Barnes maze, open-field, object recognition and location, and step-down inhibitory avoidance tasks) during nine days. In day 9, cerebral cortex and hippocampus of mice were removed to determine the thiobarbituric acid reactive species (TBARS) levels, and catalase (CAT), Na/K-ATPase and acetylcholinesterase (AChE) activities. SCO caused amnesia in mice for changing in step-down inhibitory avoidance, Barnes maze, and object recognition and object location tasks. QTCA-1 treatment attenuated the behavioral changes caused by SCO. Moreover, SCO increased AChE and CAT activities, decreased Na/K-ATPase activity and increased TBARS levels in the cerebral structures of mice. QTCA-1 protected against these brain changes. In conclusion, QTCA-1 had anti-amnesic action in the experimental model used in the present study, through the anticholinesterase effect, modulation of Na/K-ATPase activity and antioxidant action.
本研究评价了 1-(7-氯喹啉-4-基)-5-甲基-N-苯基-1H-1,2,3-三唑-4-甲酰胺 (QTCA-1) 对东莨菪碱 (SCO) 诱导的小鼠健忘症的抗健忘作用。研究评估了 QTCA-1 对小鼠大脑皮层和海马的胆碱能功能障碍、氧化应激和 Na/K-ATP 酶活性的影响。雄性瑞士小鼠用 QTCA-1（10mg/kg，灌胃，每天一次）处理 9 天。治疗 30 分钟后，动物接受 SCO（0.4mg/kg，腹腔注射）注射。SCO 注射后 30 分钟，小鼠接受行为任务（巴恩斯迷宫、旷场、物体识别和定位、以及下台阶抑制性回避任务），共 9 天。在第 9 天，取出小鼠的大脑皮层和海马，以测定硫代巴比妥酸反应性物质 (TBARS) 水平、过氧化氢酶 (CAT)、Na/K-ATP 酶和乙酰胆碱酯酶 (AChE) 活性。SCO 导致小鼠在下台阶抑制性回避、巴恩斯迷宫和物体识别和物体定位任务中出现健忘症。QTCA-1 治疗减轻了 SCO 引起的行为变化。此外，SCO 增加了小鼠大脑结构中的 AChE 和 CAT 活性，降低了 Na/K-ATP 酶活性，增加了 TBARS 水平。QTCA-1 对这些大脑变化具有保护作用。综上所述，QTCA-1 在本研究使用的实验模型中具有抗健忘作用，其作用机制是通过抗胆碱酯酶作用、调节 Na/K-ATP 酶活性和抗氧化作用。
