Protective Effects of Natsumikan (Citrus natsudaidai) Extract on Acetaminophen-induced Lethal Hepatotoxicity in Mice

Background: Like other citrus fruits, natsumikan (Citrus natsudaidai ) contains several antioxidative nutrients which occur in higher concentrations in the peel than in the pulp. A high dose of acetaminophen (APAP) generates highly reactive intermediates and causes fatal liver injury. In this study, we examined whether an extract from immature natsumikan peel prevents lethal hepatotoxicity induced by a lethal dose of APAP in mice. Materials and Methods: Male ICR mice were treated orally with natsumikan extract (300 and 1,000 mg/kg) 2, 26, and 50 hr before single oral APAP (300 mg/kg) administration. Mice were fasted for 18 hr before APAP treatment, but given tap water ad libitum. Survival was assessed for 24 hr after APAP treatment. Results: Following administration of 300 mg/kg APAP, all mice died within 6 h. However, pretreatment with natsumikan extract (300 and 1,000 mg/kg) or silymarin (300 and 1,000 mg/kg) increased the survival rate to 16.7%, 33.3%, 16.7%, and 50%, respectively, at 24 hr. Conclusion: The results suggest that natsumikan has a protective effect on APAP-induced lethal hepatotoxicity.