Meloxicam, a selective COX-2 inhibitor, displays anticonvulsive effects in pentylenetetrazole-induced acute seizures in mice through GABA and glutamate mediated mechanism

B. Sahin, R. Akkaya, S. Karabulut
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Abstract

Aim: To investigate the possible anticonvulsive effect of the selective COX-2 inhibitor meloxicam in pentylenetetrazole (PTZ)-induced epileptic seizures in mice and to examine its possible role on inhibition and excitation balance in the brain. Method: 30 BALB-c albino mice (16-18 weeks old) weighing 30-33 gr were used. Animals were randomly divided into five groups (n = 6 for each group). Group 1: control, group 2: received saline (10 ml/kg, i.p.) 30 minutes before PTZ (60 mg/kg i.p.) administration, group 3: received saline (10 ml/kg, i.p.) 30 minutes after PTZ (60 mg/kg i.p.) injection, group 4: received 60 mg/kg meloxicam i.p., 30 minutes before PTZ (60 mg/kg i.p.) administration. Group 5: received meloxicam (60 mg/kg i.p.) 30 minutes after PTZ injection (60 mg/kg, i.p.). The animals were observed for 30 minutes and the seizure stages and first myoclonic jerk times (FMJ) were recorded. After 24 hours, brain tissues were removed and the cortex and hippocampus were separated for biochemical assessments. ELISA method was used to measure GABA and glutamate levels. Results: Administration of meloxicam before PTZ induced seizure, reduced seizure stages and prolonged FMJ duration (p<0.05). Pre-treatment with meloxicam increased GABA levels in the cortex and decreased glutamate levels in the hippocampus (p<0.05). Post-treatment of meloxicam after PTZ-induced seizure increased GABA levels in the hippocampus (p<0.05). Conclusion: The results of our experimental study suggest that meloxicam has anti-convulsive effects and these effects may be mediated by GABA and glutamate, which are the main indicators of inhibition and excitation balance in the brain.
选择性COX-2抑制剂美洛昔康通过GABA和谷氨酸介导的机制对戊四唑致小鼠急性癫痫发作表现出抗惊厥作用
目的:探讨选择性COX-2抑制剂美洛昔康对戊四唑(PTZ)致小鼠癫痫发作的抗惊厥作用,并探讨其在脑内抑制和兴奋平衡中的可能作用。方法:选取BALB-c型白化小鼠30只,年龄16 ~ 18周龄,体重30 ~ 33 g。实验动物随机分为5组,每组6只。组1:对照组,组2:在PTZ (60 mg/kg)给药前30分钟给予生理盐水(10 ml/kg, i.p),组3:PTZ (60 mg/kg i.p)注射后30分钟给予生理盐水(10 ml/kg, i.p),组4:在PTZ (60 mg/kg)给药前30分钟给予美洛昔康60 mg/kg i.p。第5组:PTZ注射后30分钟给予美洛昔康(60mg /kg, i.p)。观察30分钟,记录癫痫发作阶段和第一次肌阵挛抽搐次数。24小时后,取脑组织,分离皮质和海马进行生化评估。ELISA法测定GABA和谷氨酸水平。结果:PTZ前给予美洛昔康可减少癫痫发作期,延长FMJ持续时间(p<0.05)。美洛昔康预处理增加了皮质GABA水平,降低了海马谷氨酸水平(p<0.05)。ptz诱导癫痫发作后给予美洛昔康后,海马GABA水平升高(p<0.05)。结论:本实验结果提示美洛昔康具有抗惊厥作用,其作用机制可能是GABA和谷氨酸介导的,而GABA和谷氨酸是脑内抑制和兴奋平衡的主要指标。
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