Abstract:Background: Acetaminophen is an analgesic drug that is used safely in therapeutic doses. At high doses, it causes hepatotoxicity, resulting in hepatic necrosis. Some medications and methods are available for treatment of acetaminophen overdose. However, results are inconsistent, and suffi cient outcomes cannot always be obtained. Objective: The mechanism of action of acetaminophen has not been fully understood. It has been suggested that it exerts its effects on GABA receptors. Flumazenil has been experimentally proven to produce an antagonism on acetaminophen's analgesic effect. The purpose of this study was to determine whether fl umazenil antagonized the toxic effects of acetaminophen overdose in rats. Methods: A total of 49 Wistar albino rats weighing between 250 -350 g were used in the study. Nine rats were examined for a preliminary study, and the other rats were randomly divided into fi ve groups with eight subjects in each. Control group: Saline; Acetaminophen group: 3 g/kg acetaminophen; Experimental Group F1: 3 g/kg acetaminophen + 0.1 mg/kg fl umazenil; Experimental group F2: 3 g/kg acetaminophen + 1 mg/kg fl umazenil; Experimental group F3: 3 g/kg acetaminophen + 10 mg/kg fl umazenil. Acetaminophen was administered in a 3 ml saline solution by way of gastric catheter. Flumazenil was administered by way of intraperitoneal injections. Serum levels of acetaminophen, AST, ALT, LDH, ALP and bilirubin were recorded over a 24-hour period. Results: Serum acetaminophen levels were similar between the groups. The AST, ALT, ALP, LDH, total bilirubin and direct bilirubin levels of Group A were signifi cantly higher compared with the Group C, Group F1, Group F2 and Group F3. There was not a statistically signifi cant difference in the AST, ALT, ALP, LDH, total bilirubin or direct bilirubin levels of the fl umazenil-administered groups. Conclusion: Flumazenil's prevention of the acetaminophen-induced increase in liver enzymes is promising. There is some indication that fl umazenil could be used in treatment of acetaminophen intoxication (Tab. 2, Ref. 25). Full Text in PDF www.elis.sk.