Suppressive effect of kamebakaurin on acetaminophen-induced hepatotoxicity by inhibiting lipid peroxidation and inflammatory response in mice

Background kamebakaurin (ka) is an ent-kaurane diterpenoid known to have anti-inflammatory potential. in the current study,we investigated whether pretreatment with ka could ameliorate acetaminophen (apap)-induced hepatotoxicity by inhibiting the anti-inflammatory response in mice. methods seven-week-old c57bl/6j mice were orally administered ka or olive oil emulsion for seven days. twenty-four hours after the last ka or olive oil administration,the mice were intraperitoneally injected with 400 mg/kg apap or saline under feed deprived condition. the mice from each group were euthanized and bled for plasma analysis 24 h after the injection. result apap increased plasma levels of hepatic injury markers (i.e.,alanine aminotransferase and aspartate aminotransferase),lipid peroxidation,and pro-inflammatory cytokines. pretreatment with ka reduced the magnitude of apap-induced increases in plasma levels of hepatic injury markers,lipid peroxidation,and inflammatory response. in addition,ka exhibited antioxidant capacity in a dose-dependent manner,with slight reactive oxygen species scavenging activity. conclusion our results indicate that ka has the ability to protect the liver from apap-induced hepatotoxicity,presumably by both inhibiting the inflammatory response and oxidative stress. © 2017 institute of pharmacology,polish academy of sciences