title: The effect of different doses of flumazenil on acetaminophen toxicity in rats.
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 sufficient 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 flumazenil 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 five groups with eight subjects in each.
  
  
  METHODS
  Saline; Acetaminophen group: 3 g/kg acetaminophen; Experimental Group F1: 3 g/kg acetaminophen + 0.1 mg/kg flumazenil; Experimental group F2: 3 g/kg acetaminophen + 1 mg/kg flumazenil; Experimental group F3: 3 g/kg acetaminophen + 10 mg/kg flumazenil. 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 significantly higher compared with the Group C, Group F1, Group F2 and Group F3. There was not a statistically significant difference in the AST, ALT, ALP, LDH, total bilirubin or direct bilirubin levels of the flumazenil-administered groups.
  
  
  CONCLUSIONS
  Flumazenil's prevention of the acetaminophen-induced increase in liver enzymes is promising. There is some indication that flumazenil could be used in treatment of acetaminophen intoxication (Tab. 2, Ref. 25).
authors.affiliation: Department of Anesthesiology, Erciyes University Medical Faculty, Kayseri, Turkey.
authors.forename: E
authors.initials: E
authors.lastname: Bozogluer
authors.forename: H
authors.initials: H
authors.lastname: Madenoglu
authors.forename: R
authors.initials: R
authors.lastname: Aksu
authors.forename: C
authors.initials: C
authors.lastname: Bicer
authors.forename: C
authors.initials: C
authors.lastname: Yazici
authors.forename: A
authors.initials: A
authors.lastname: Boyaci
mesh_terms: D000082:Acetaminophen / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D018712:Analgesics, Non-Narcotic / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D000818:Animals; D000931:Antidotes / Q000627:therapeutic use*; D005442:Flumazenil / Q000627:therapeutic use*; D008099:Liver / Q000187:drug effects; D008111:Liver Function Tests; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018712:Analgesics, Non-Narcotic; D000931:Antidotes; D000082:Acetaminophen; D005442:Flumazenil