Department of Anesthesiology and Reanimation, Akdeniz University, Antalya, Turkey.
Department of Biophysics, Akdeniz University, Antalya, Turkey.
Daru. 2021 Jun;29(1):85-99. doi: 10.1007/s40199-020-00385-2. Epub 2021 Jan 19.
This study investigated whether thymoquinone (TQ) could alleviate central nervous system (CNS) and cardiovascular toxicity of prilocaine, a commonly used local anesthetic.
Rats were randomized to the following groups: control, prilocaine treated, TQ treated and prilocaine + TQ treated. Electroencephalography and electrocardiography electrodes were placed and trachea was intubated. Mechanical ventilation was initiated, right femoral artery was cannulated for continuous blood pressure measurements and blood-gas sampling while the left femoral vein was cannulated for prilocaine infusion. Markers of myocardial injury, reactive oxygen/nitrogen species (ROS/RNS) generation and total antioxidant capacity (TAC) were assayed by standard kits. Aquaporin-4 (AQP4), nuclear factor(NF)κB-p65 and -p50 subunit in brain tissue were evaluated by histological scoring.
Blood pH and partial oxygen pressure, was significantly decreased after prilocaine infusion. The decrease in blood pH was alleviated in the prilocaine + TQ treated group. Prilocaine produced seizure activity, cardiac arrhythmia and asystole at significantly lower doses compared to prilocaine + TQ treated rats. Thymoquinone administration attenuated levels of myocardial injury induced by prilocaine. Prilocaine treatment caused increased ROS/RNS formation and decreased TAC in heart and brain tissue. Thymoquinone increased heart and brain TAC and decreased ROS/RNS formation in prilocaine treated rats. AQP4, NFκB-p65 and NFκB-p50 expressions were increased in cerebellum, cerebral cortex, choroid plexus and thalamic nucleus in prilocaine treated rats. Thymoquinone, decreased the expression of AQP4, NFκB-p65 and NFκB-p50 in brain tissue in prilocaine + TQ treated rats.
Results indicate that TQ could ameliorate prilocaine-induced CNS and cardiovascular toxicity.
本研究旨在探讨百里醌（TQ）是否可以减轻普鲁卡因（一种常用的局部麻醉剂）引起的中枢神经系统（CNS）和心血管毒性。
将大鼠随机分为以下几组：对照组、普鲁卡因处理组、TQ 处理组和普鲁卡因+TQ 处理组。放置脑电图和心电图电极，并进行气管插管。启动机械通气，右股动脉插管进行连续血压测量和血气取样，同时左股静脉插管进行普鲁卡因输注。通过标准试剂盒测定心肌损伤标志物、活性氧/氮物种（ROS/RNS）生成和总抗氧化能力（TAC）。通过组织学评分评估脑组织中水通道蛋白-4（AQP4）、核因子（NF）κB-p65 和-p50 亚基。
普鲁卡因输注后血液 pH 值和部分氧分压明显降低。在普鲁卡因+TQ 处理组中，血液 pH 值的降低得到缓解。与普鲁卡因+TQ 处理组大鼠相比，普鲁卡因以明显更低的剂量引起癫痫发作活动、心律失常和心搏停止。TQ 给药可减轻普鲁卡因引起的心肌损伤水平。普鲁卡因处理导致心脏和脑组织中 ROS/RNS 形成增加和 TAC 降低。TQ 增加了普鲁卡因处理大鼠的心脏和大脑 TAC，并减少了 ROS/RNS 的形成。在普鲁卡因处理的大鼠的小脑、大脑皮层、脉络丛和丘脑核中，AQP4、NFκB-p65 和 NFκB-p50 的表达增加。TQ 降低了普鲁卡因+TQ 处理大鼠脑组织中 AQP4、NFκB-p65 和 NFκB-p50 的表达。
结果表明，TQ 可以改善普鲁卡因引起的中枢神经系统和心血管毒性。
