Alleviation of prilocaine-induced epileptiform activity and cardiotoxicity by thymoquinone.

Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences Pub Date : 2021-06-01 Epub Date: 2021-01-19 DOI:10.1007/s40199-020-00385-2

Barış Akgül, İlker Öngüç Aycan, Enis Hidişoğlu, Ebru Afşar, Sendegül Yıldırım, Gamze Tanrıöver, Nesil Coşkunfırat, Suat Sanlı, Mutay Aslan

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Abstract

Purpose: This study investigated whether thymoquinone (TQ) could alleviate central nervous system (CNS) and cardiovascular toxicity of prilocaine, a commonly used local anesthetic.

Methods: 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.

Results: 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.

Conclusion: Results indicate that TQ could ameliorate prilocaine-induced CNS and cardiovascular toxicity.

查看原文本刊更多论文

胸腺醌可减轻普鲁卡因诱发的癫痫样活动和心脏毒性。

目的：本研究探讨胸腺醌（TQ）能否减轻常用局麻药普鲁卡因对中枢神经系统（CNS）和心血管的毒性：将大鼠随机分为以下几组：对照组、利多卡因处理组、胸腺醌处理组和利多卡因+胸腺醌处理组。放置脑电图和心电图电极并插管气管。开始机械通气，插管右股动脉进行连续血压测量和血气采样，同时插管左股静脉进行普鲁卡因输注。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）均通过标准试剂盒进行检测。通过组织学评分评估脑组织中的水汽素-4（AQP4）、核因子（NF）κB-p65 和 -p50 亚基：结果：输注普鲁卡因后，血液pH值和氧分压明显下降。普鲁卡因+TQ治疗组的血液pH值下降有所缓解。与普鲁卡因+TQ治疗组大鼠相比，普鲁卡因产生癫痫活动、心律失常和心搏骤停的剂量明显较低。服用胸腺醌可减轻普鲁卡因引起的心肌损伤程度。普鲁卡因治疗会导致心脏和脑组织中的 ROS/RNS 形成增加，TAC 减少。胸腺醌可增加普鲁卡因治疗大鼠的心脏和大脑TAC，减少ROS/RNS的形成。普鲁卡因治疗大鼠的小脑、大脑皮层、脉络丛和丘脑核中的 AQP4、NFκB-p65 和 NFκB-p50 表达增加。胸腺醌可降低普鲁卡因+TQ治疗大鼠脑组织中AQP4、NFκB-p65和NFκB-p50的表达：结果表明，TQ 可改善普鲁卡因诱导的中枢神经系统和心血管毒性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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Daru : journal of Faculty of Pharmacy, Tehran University of Medical Sciences

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