Pelargonidin ameliorates acetaminophen-induced hepatotoxicity in mice by inhibiting the ROS-induced inflammatory apoptotic response

Abstract

The common analgesic acetaminophen (N-acetyl-p-aminophenol, APAP) is non-toxic to the liver at therapeutic doses. However, an overdose of APAP can lead to APAP-induced liver failure, which has emerged as a serious issue in the US and Europe. Pelargonidin is an anthocyanidin found in pomegranates, plums, and various berries. Pelargonidin has strong antioxidant effects, directly scavenging superoxide radicals and inhibiting H2O2-induced lipid peroxidation. Focusing on these effects, we studied the preventative effect of pelargonidin on APAP-induced hepatotoxicity and its underlying mechanisms in vivo. We observed that pelargonidin mitigates serum alanine aminotransferase and aspartate aminotransferase activity, which are strongly associated with APAP-induced hepatotoxicity. We also found that pelargonidin reduced APAP-induced hepatic necrosis by removing excessive ROS. Hepatic necrosis stimulates the release of molecular pathogens that induce inflammation, which increases cell stress and can lead to apoptosis. Therefore, pelargonidin was able to reduce levels of necrosis, inflammation, and hepatocyte apoptosis. These results indicate that the administration of pelargonidin protects against APAP-induced hepatotoxicity and that it could be a novel protective strategy against APAP-induced liver failure. (C) 2019 Elsevier B.V. and Societe Francaise de Biochimie et Biologie Moleculaire (SFBBM). All rights reserved.