title: Attenuating Oxidative Stress by Paeonol Protected against Acetaminophen-Induced Hepatotoxicity in Mice.
abstract: Acetaminophen (APAP) overdose is the most frequent cause of drug-induced acute liver failure. The purpose of this study was to investigate whether paeonol protected against APAP-induced hepatotoxicity. Mice treated with paeonol (25, 50, 100 mg/kg) received 400 mg/kg acetaminophen intraperitoneally (i.p.) and hepatotoxicity was assessed. Pre-treatment with paeonol for 6 and 24 h ameliorated APAP-induced hepatic necrosis and significantly reduced the serum alanine aminotransferase (ALT) and aspartate transaminase (AST) levels in a dose-dependent manner. Post-treatment with 100 mg/kg paeonol ameliorated APAP-induced hepatic necrosis and reduced AST and ALT levels in the serum after APAP administration for 24 h. Western blot revealed that paeonol inhibited APAP-induced phosphorylated JNK protein expression but not p38 and Erk1/2. Moreover, paeonol showed anti-oxidant activities with reducing hepatic MDA contents and increasing hepatic SOD, GSH-PX and GSH levels. Paeonol dose-dependently prevented against H2O2 or APAP-induced LDH releasing and ROS production in primary mouse hepatocytes. In addition, the mRNA levels of pro-inflammatory genes such as TNF-α, MCP-1, IL-1β and IL-6 in the liver were dose-dependently reduced by paeonol pre-treatment. Pre-treatment with paeonol significantly inhibited IKKα/β, IκBα and p65 phosphorylation which contributed to ameliorating APAP-induced hepatic inflammation. Collectively, the present study demonstrates paeonol has a protective ability against APAP-induced hepatotoxicity and might be an effective candidate compound against drug-induced acute liver failure.
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathology, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Yuning
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Modern Medical Research Center, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhi
authors.affiliation: Department of Geriatrics, Third Affiliated Hospital of Soochow University, Changzhou, China.
authors.forename: Ke
authors.initials: K
authors.lastname: Qian
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage / Q000633:toxicity*; D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology*; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D004195:Disease Models, Animal; D005978:Glutathione / Q000378:metabolism; D005979:Glutathione Peroxidase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D000098:Acetophenones; D018712:Analgesics, Non-Narcotic; D016328:NF-kappa B; D000082:Acetaminophen; C013638:paeonol; D008315:Malondialdehyde; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D005978:Glutathione