title: 5-lipoxygenase activation is involved in the mechanisms of chronic hepatic injury in a rat model of chronic aluminum overload exposure.
abstract: We previously confirmed that rats overloaded with aluminum exhibited hepatic function damage and increased susceptibility to hepatic inflammation. However, the mechanism of liver toxicity by chronic aluminum overload is poorly understood. In this study, we investigated changes in the 5-lipoxygenase (5-LO) signaling pathway and its effect on liver injury in aluminum-overloaded rats. A rat hepatic injury model of chronic aluminum injury was established via the intragastric administration of aluminum gluconate (Al(3+) 200mg/kg per day, 5days a week for 20weeks). The 5-LO inhibitor, caffeic acid (10 and 30mg/kg), was intragastrically administered 1h after aluminum administration. Hematoxylin and eosin staining was used to visualize pathological changes in rat liver tissue. A series of biochemical indicators were measured with biochemistry assay or ELISAs. Immunochemistry and RT-PCR methods were used to detect 5-LO protein and mRNA expression in the liver, respectively. Caffeic acid administration protected livers against histopathological injury, decreased plasma ALT, AST, and ALP levels, decreased TNF-α, IL-6, IL-1β and LTs levels, increased the reactive oxygen species content, and down-regulated the mRNA and protein expressions of 5-LO in aluminum overloaded rats. Our results indicate that 5-lipoxygenase activation is mechanistically involved in chronic hepatic injury in a rat model of chronic aluminum overload exposure and that the 5-LO signaling pathway, which associated with inflammation and oxidative stress, is a potential therapeutic target for chronic non-infection liver diseases.
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Shaoshan
authors.initials: S
authors.lastname: Mai
authors.affiliation: Department of Heptobiliary Surgery, 1st Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: He
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Xinyue
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Luo
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Shengnan
authors.initials: S
authors.lastname: Kuang
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Tian
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Pharmacology, Chongqing Medical University, Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing 400016, China. Electronic address: 1139627371@qq.com.
authors.forename: Junqing
authors.initials: J
authors.lastname: Yang
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics / Q000378:metabolism*; D001219:Aspartate Aminotransferases / Q000097:blood; D002109:Caffeic Acids / Q000494:pharmacology; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D007975:Leukotriene B4 / Q000378:metabolism; D017997:Leukotriene C4 / Q000378:metabolism; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002109:Caffeic Acids; D016207:Cytokines; D016859:Lipoxygenase Inhibitors; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D007975:Leukotriene B4; D017997:Leukotriene C4; D008315:Malondialdehyde; D000535:Aluminum; D001094:Arachidonate 5-Lipoxygenase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase; C040048:caffeic acid
keywords: 5-Lipoxygenase; Caffeic acid; Chronic aluminum load; Inflammation; Liver function; Oxidative stress