Prilocaine induced epileptiform activity and cardiac toxicity is alleviated by thymoquinone treatment.

Yıldırım, Sendegül; Tanrıöver, Gamze; Akgül, Barış; Aycan, İlker Öngüç; Hidişoğlu, Enis; Afşar, Ebru; Aslan, Mutay

Objective: The aim of this study was to investigate whether thymoquinone (TQ) could alleviate prilocaine-induced (PRL) central nervous system, cardiovascular toxicity in anaesthetized rats. Methods: With the approval of the Local Ethics Committee of the Animal Experiments of Akdeniz University; Rats were randomized to following groups: Control, PRL, TQ, PRL TQ treated. Rats were anesthetized intraperitoneally. Fronto-occipital EEG and ECG electrodes were placed and the trachea was intubated. Mechanical ventilation was initiated with a tidal volume of ' 0 mg/kg and a rate of 50-55 breaths/min. Right femoral artery was cannulated for continuous blood pressure measurements and blood-gas sampling while the left femoral artery was cannulated for PRL infusion (8 mg/kg/min).TQ was given by gavage (15 mg/kg per day) for 3 days prior to drug administration. Arterial blood sample for blood gas analysis was drawn before drug infusion, during drug infusion and after cardiac arrest. Markers of myocardial injury, oxygen/nitrogen species generation, total antioxidant capacity were assayed by standard kits. AQP4, NFKBp65, p50 subunit in brain tissue were evaluated by immunohistochemically. Results: Blood pH,partial oxygen pressure was significantly decreased after PRL infusion. The decrease in blood pH was alleviated in the PRL TQ group.PRL produced seizure activity on EEG at significantly lower doses compared to PRL TQ rats. Cardiac arrhythmia, asystole on ECG occured at significantly lower doses in the PRL. PRL caused as significant increase in serum myoglobin, CK-MB levels. PRL TQ treatment attenuated levels of myocardial injury.PRL caused increased ROS/RNS formation and decreased TAC in the heart, brain tissues.TQ increased heart, brain TAC and decreased ROS/RNS formation in PRL groups. AQP4, p50, p65 expressions were increased in cerebellar, cerebral cortex, choroid plexus in PRL treated rats. PRL TQ decreased the expression of AQP4, p50, p65 in brain tissue (p<0.05). One-way Anova test was used for statistical significance between groups. Conclusion: The data shows that TQ is a protective agent against prilocaine-induced CNS and cardiovascular toxicity.TQ could ameliorate CNS and cardiac toxicity induced by high dose PRL treatment.

THERAPEUTICS; OXIDANT status; BIOPOTENTIALS (Electrophysiology); CENTRAL nervous system; ARRHYTHMIA; CEREBRAL cortex

Anatomy: International Journal of Experimental & Clinical Anatomy, 2019, Vol 13, Issue S1, pS31

1307-8798

Academic Journal