title: Resolvin D1 attenuates CCl4-induced acute liver injury involving up-regulation of HO-1 in mice.
abstract: Acute hepatic failure involves in excessive oxidative stress and inflammatory responses, leading to a high mortality due to lacking effective therapy. Resolvin D1 (RvD1), an endogenous lipid mediator derived from polyunsaturated fatty acids, has been shown anti-inflammatory and anti-oxidative actions, however, whether RvD1 has protective effects on hepatic failure remains elusive. In this study, the roles and molecular mechanisms of RvD1 were explored in carbon tetrachloride (CCl4)-induced acute liver injury. Our results showed that RvD1 protected mice against CCl4-induced hepatic damage, as evaluated by reduced aminotransferase activities and malondialdehyde content, elevated glutathione and superoxide dismutase activities, and alleviated hepatic pathological damage. Moreover, RvD1 significantly attenuated serum tumor necrosis factor-α and interleukin-6 levels as well as hepatic myeloperoxidase activity, whereas enhanced serum IL-10 level in CCl4-administered mice. Further, RvD1 markedly up-regulated the expression and activity of heme oxygenase-1 (HO-1). However, inhibition of HO-1 activity reversed the protective effects of RvD1 on CCl4-induced liver injury. These results suggest that RvD1 could effectively prevent CCl4-induced liver injury by inhibition of oxidative stress and inflammation, and the underlying mechanism may be related to up-regulation of HO-1.
authors.affiliation: a Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University , Chongqing , China .
authors.forename: Xiahong
authors.initials: X
authors.lastname: Chen
authors.affiliation: b Department of Anatamy , Chongqing Medical University , Chongqing , China .
authors.forename: Xia
authors.initials: X
authors.lastname: Gong
authors.affiliation: c Laboratory of Stem Cell and Tissue Engineering , Chongqing Medical University , Chongqing , China .
authors.forename: Rong
authors.initials: R
authors.lastname: Jiang
authors.affiliation: d Department of Anesthesiology , the First Affiliated Hospital, Chongqing Medical University , Chongqing , China , and.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: a Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University , Chongqing , China .
authors.forename: Ge
authors.initials: G
authors.lastname: Kuang
authors.affiliation: e Department of Orthopaedics , the First Affiliated Hospital, Chongqing Medical University , Chongqing , China.
authors.forename: Ke
authors.initials: K
authors.lastname: Li
authors.affiliation: a Chongqing Key Laboratory of Biochemistry and Molecular Pharmacology, Chongqing Medical University , Chongqing , China .
authors.forename: Jingyuan
authors.initials: J
authors.lastname: Wan
mesh_terms: D000818:Animals; D002252:Carbon Tetrachloride Poisoning / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D016207:Cytokines / Q000096:biosynthesis; D004281:Docosahexaenoic Acids / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D017114:Liver Failure, Acute / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D018384:Oxidative Stress / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D016207:Cytokines; D008565:Membrane Proteins; C518399:resolvin D1; D004281:Docosahexaenoic Acids; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Acute liver injury; anti-inflammatory; carbon tetrachloride (CCl4); heme oxygenase-1 (HO-1); resolvin D1 (RvD1)