Davallialactone protects against acetaminophen overdose-induced liver injuries in mice

Oxidative stress is closely associated with acetaminophen (APAP)-induced toxicity. Davallialactone (DAVA), a hispidin analog derived from the mushroom Inonotus xeranticus, has antioxidant properties. This study evaluated whether DAVA plays protective roles against APAP hepatotoxicity in mice. Pretreatments with DAVA (10 mg/kg) prior to exposures of mice to a hepatotoxic dose of 600 mg/kg APAP significantly increased survival rate compared to APAP alone. To verify this effect, mice were treated with 400 mg/kg APAP 30 min after DAVA administration and were then sacrificed after 0.5, 1, 3, and 6 h. APAP alone caused severe liver injuries as characterized by increased plasma GOT and GPT levels, ATP and GSH depletion, and peroxynitrite and 4-HNE formations. These liver damages induced by APAP were significantly attenuated by DAVA pretreatments. The GSH/GSSG ratio nearly recovered to the levels observed in non-APAP-treated mice at 6 h after APAP treatment in DAVA-pretreated mice. Furthermore, while hepatic ROS levels were increased by APAP exposures, pretreatments with DAVA completely blocked ROS formation. In addition, APAP-induced sustained activations of JNK and ERK were remarkably reduced by DAVA pretreatment. In conclusion, these results suggest that DAVA plays protective roles against APAP-mediated hepatotoxicity through function as ROS scavenger.