Evaluation of in vitro hepatotoxicity of perampanel in comparison with carbamazepine: old versus new

Abstract

Since the liver metabolizes many drugs, including antiepileptics, this organ is the main target of drug-induced damage. There is very little data on hepatotoxicity due to carbamazepine and perampanel metabolized in the liver. The available data are based solely on published case reports. For this reason, this study aims to evaluate the hepatotoxicity of carbamazepine and perampanel, which are frequently used in treating epilepsy and which do not have a detailed investigation, although they are suspected of hepatotoxicity. Hepatotoxicity in the HepG2 cell line, IC50 values were calculated by MTT cytotoxicity test, followed by determination of apoptosis/necrosis, various biochemical analyzes (ALT, AST, urea), which is currently a biomarker for liver injury, and hepatotoxicity by ROS and GSH determination. Both drugs increased liver biomarkers, oxidative stress, and cytotoxicity in HepG2 cells. The investigation found that the drugs triggered liver apoptosis, not necrosis. In conclusion, Perampanel may have hepatotoxicity similar to carbamazepine.