Published online Sep 27, 2020. doi: 10.4254/wjh.v12.i9.596
Peer-review started: November 28, 2019
First decision: December 30, 2019
Revised: June 29, 2020
Accepted: August 25, 2020
Article in press: August 25, 2020
Published online: September 27, 2020
Processing time: 297 Days and 20 Hours
Acetaminophen overdose is the most frequent cause of drug-induced liver failure in the developed countries. Despite substantial progress in the understanding of the mechanism of hepatocellular injury, N-acetylcysteine remains the only effective treatment if administered within 8 h to 10 h of acetaminophen ingestion. Thus, other hepatoprotective drugs are needed for the delayed treatment of acetaminophen-induced hepatotoxicity.
Our interest focused on glycyrrhizin for its role as an inhibitor of high mobility group box 1 protein, a member of the family of damage associated molecular pattern, known to play important pathological roles in different diseases.
The present study aimed to investigate the efficacy of the N-acetylcysteine/ glycyrrhizin combination compared to N-acetylcysteine alone in the prevention of liver toxicity.
Eight-week-old C57BL/6J wild-type female mice were used for all our experiments. Mice fasted for 15 h were treated with acetaminophen (500 mg/kg) or vehicle (phosphate-buffered saline) by intraperitoneal injection and separated into the following groups: Glycyrrhizin (200 mg/kg); N-acetylcysteine (150 mg/kg); and N-acetylcysteine/glycyrrhizin. Hepatotoxicity was assessed by biochemical and histopathological analyses. Survival rates were also compared.
In C57BL/6J mice, glycyrrhizin administration was shown to reduce the release of HMGB1 and to significantly decrease the severity of acetaminophen-induced liver injury. Thus, the co-administration of glycyrrhizin and N-acetylcysteine was investigated. Administered concomitantly with acetaminophen, the combination significantly reduced the severity of liver injury. Delayed administration of the combination of drugs, 2 h or 6 h after acetaminophen, also induced a significant decrease in hepatocyte necrosis compared to mice treated with N-acetylcysteine alone. In addition, administration of N-acetylcysteine/glycyrrhizin combination was associated with an improved survival rate compared to mice treated with only N-acetylcysteine.
Compared to N-acetylcysteine alone, co-administration of glycyrrhizin decreases the liver necrosis score and improves survival in our murine model of acetaminophen-induced liver injury.
Further experiments are needed to better investigate the efficacy of the N-acetylcysteine/glycyrrhizin combination, but these results suggest for the first time that the combination of an antioxidant like N-acetylcysteine and an anti-inflammatory drug like glycyrrhizin prevents the liver damage induced by acetaminophen intoxication.