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

Autor: Akgül, Barış, Aycan, İlker Öngüç, Hidişoğlu, Enis, Afşar, Ebru, Yıldırım, Sendegül, Tanrıöver, Gamze, Coşkunfırat, Nesil, Sanlı, Suat, Aslan, Mutay
Předmět:
Zdroj: DARU: Journal of Pharmaceutical Sciences; 1/19/2021, Vol. 29, p85-99, 15p
Abstrakt: 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. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index