title: Protective effects of luteolin against acetaminophen-induced acute liver failure in mouse.
abstract: Acetaminophen (APAP) is widely used as a safety analgesic and antipyretic agent. Although considered safe at therapeutic doses, overdose of APAP can cause acute liver injury that is sometimes fatal, requiring efficient pharmacological intervention. Luteolin is a naturally occurring flavonoid which is abundant in plants. The objective of this study was to investigate corresponding anti-oxidative and anti-inflammatory activities of luteolin, using acetaminophen-treated mice as a model system. Male C57BL/C mice were randomly divided into three groups (n=6 each). The control group was given phosphate buffered saline (PBS) orally. The APAP group was given APAP by intraperitoneal injection (i.p) at 300 mg/kg suspended in PBS. The luteolin-treated group was given APAP and luteolin (0-100 mg/kg/day, 1 or 3 days before APAP administration) suspended in PBS orally. 16 h after APAP administration, the liver and serum were collected to determine the liver injury. Luteolin administration significantly decreased acetaminophen-induced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), malondialdehyde (MDA) levels, as well as glutathione (GSH) depletion and decrease of superoxide dismutase (SOD). Luteolin restored SOD, GSH and GSH-px activities and depressed the expression of pro-inflammatory factors, such as inducible nitric oxide synthase (i-NOS), TNF-α, nuclear factor kappa B (NF-κB), and IL-6, respectively. Moreover, luteolin down-regulated acetaminophen-induced nitrotyrosine (NT) formation and endoplasmic reticulum (ER) stress. These results suggest the presence of anti-oxidative, anti-inflammatory and anti-ER stress properties of luteolin in response to acetaminophen-induced liver injury in mice.
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: Minghui
authors.initials: M
authors.lastname: Tai
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: Jingyao
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: Sidong
authors.initials: S
authors.lastname: Song
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: RunChen
authors.initials: R
authors.lastname: Miao
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: Sushun
authors.initials: S
authors.lastname: Liu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Pang
authors.affiliation: Department of Thoracic Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China.
authors.forename: Qifei
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, People's Republic of China. Electronic address: liuchangdoctor@gmail.com.
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage; D000410:Alanine Transaminase / Q000378:metabolism; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D001219:Aspartate Aminotransferases / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D004195:Disease Models, Animal; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008099:Liver / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D047311:Luteolin / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000082:Acetaminophen; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D047311:Luteolin
keywords: Acetaminophen; Endoplasmic reticulum stress; Luteolin; Reactive oxygen species