title: Davallialactone protects against acetaminophen overdose-induced liver injuries in mice.
abstract: 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 6h 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.
authors.affiliation: Laboratory Animal Center, Korea Research Institute of Bioscience and Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors.forename: Jung-Ran
authors.initials: JR
authors.lastname: Noh
authors.forename: Yong-Hoon
authors.initials: YH
authors.lastname: Kim
authors.forename: Jung Hwan
authors.initials: JH
authors.lastname: Hwang
authors.forename: Gil-Tae
authors.initials: GT
authors.lastname: Gang
authors.forename: Kyoung-Shim
authors.initials: KS
authors.lastname: Kim
authors.forename: In-Kyoung
authors.initials: IK
authors.lastname: Lee
authors.forename: Bong-Sik
authors.initials: BS
authors.lastname: Yun
authors.forename: Chul-Ho
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000082:Acetaminophen / Q000506:poisoning*; D000255:Adenosine Triphosphate / Q000097:blood; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D062787:Drug Overdose / Q000517:prevention & control*; D005978:Glutathione / Q000097:blood; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D015996:Survival Rate
chemical_list: D007783:Lactones; C068766:davallialactone; D000082:Acetaminophen; D000255:Adenosine Triphosphate; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D005978:Glutathione
keywords: Acetaminophen; Davallialactone; Liver; Oxidative stress; Toxicity