Barış Akgül1, İlker Öngüç Aycan1, Enis Hidişoğlu2, Ebru Afşar3, Sendegül Yıldırım4, Gamze Tanrıöver4, Nesil Coşkunfırat1, Suat Sanlı1, Mutay Aslan5. 1. Department of Anesthesiology and Reanimation, Akdeniz University, Antalya, Turkey. 2. Department of Biophysics, Akdeniz University, Antalya, Turkey. 3. Department of Medical Biochemistry, Akdeniz University Medical School, 07070, Antalya, Turkey. 4. Department of Histology and Embryology, Akdeniz University, Antalya, Turkey. 5. Department of Medical Biochemistry, Akdeniz University Medical School, 07070, Antalya, Turkey. mutayaslan@akdeniz.edu.tr.
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.
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.
Entities:
Keywords:
Cardiovascular; Central nervous system; Prilocaine; Thymoquinone; Toxicity
Authors: Uz Ebru; Uz Burak; Selcoki Yusuf; Bayrak Reyhan; Kaya Arif; Turgut H Faruk; Mete Emin; Karanfil Aydin; I Ihan Atilla; Sahin Semsettin; Erdemli Kemal Journal: Basic Clin Pharmacol Toxicol Date: 2008-12 Impact factor: 4.080