Protective effectiveness of thymoquinone in prilocaine toxicity

Prilocaine is widely used for local anesthesia and amide type local anesthetic is used safely at therapeutic doses. It is metabolized in the liver and its toxicity is very low. However, when used in high doses for intravenous regional anesthesia, it may cause central and cardiac toxic effects. Thymoquinone (TQ) is a potent antioxidant derived from the Nigella sativa seed. TQ has a protective effect against doxorubicin-induced cardiotoxicity. In addition, TQ has been shown to prevent penicillin-induced epilepsy. The aim of this study was to investigate the efficacy of TQ in prilocaine induced central nervous system (CNS) and cardiovascular toxicity. 40 male Wistar rats weighing 350-450 g were used in the study. Rats were randomly divided into 4 groups: Sham (S, n=10), Prilocaine (P, n=10), TQ (T, n=10) and Prilocaine + TQ (TP, n=10). EEG, ECG and haemodynamic monitoring were performed in rats under general anesthesia after necessary catheterization and electrode placement procedures. EEG, ECG and invasive blood pressure were recorded during the experiment. Heart and brain tissues were removed for biochemical and immunohistochemical studies after sacrification of animals, and serum samples taken. At the end of the study, it was found that thymoquinone significantly delayed epileptiform activity and isoelectric EEG formation due to prilocaineinduced neurotoxicity, and significantly increased the amount of prilocaine required for first arrhythmia and asystole with signs of cardiotoxicity. In addition, thymoquinone was found to increase Total Antioxidant Capacity levels and AQP4, p50 and p65 expressions, which are brain edema and neuroinflammation markers caused by neurotoxicity, were significantly reduced. As a result, thymoquinone in prilocaine toxicity; showed cardioprotective, antiarrhythmic, neuroprotective and antiepileptic properties. In this information, we think that thymoquinone, which is a lipid structure, can be used as an alternative to lipid solutions in local anesthetic toxicity. However, further studies are needed on the clinical use of thymoquinone. Key Words: Prilocaine, Thymoquinone, Epileptiform, Cardiotoxicity, Neurotoxicity