title: BML-111 Protected LPS/D-GalN-Induced Acute Liver Injury in Rats.
abstract: Lipoxins (LXs) display unique pro-resolving and anti-inflammatory functions in a variety of inflammatory conditions. The present study was undertaken to investigate the effects of BML-111 (5(S),6(R),7-trihydroxyheptanoic acid methyl ester), the agonist of lipoxin A₄ receptor, in a model of Lipopolysaccharides (LPS) and d-Galactosamine (d-GalN) induced acute liver injury, and to explore the mechanisms. Histopathological analyses were carried out to quantify liver injury degree. The activities of myeloperoxidase (MPO) were examined to evaluate the levels of neutrophil infiltration. The activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in serum were detected to evaluate the functions of the liver. The amounts of tumor necrosis factor-α (TNF-α), interleukin-10 (IL-10), and interleukin-1β (IL-1β) were measured using enzyme-linked immunosorbent assay (ELISA), and the expression levels of transforming growth factor-β1(TGF-β1) and cyclooxygenase-2 (COX-2) were examined using Western blotting. The antioxidant capacity, the activities of inducible nitric oxide synthase (iNOS), the contents of malondialdehyde (MDA) and nitric oxide (NO) were analyzed with the kits via biochemical analysis. We established the model of acute liver injury with lipopolysaccharide and d-Galactosamine (LPS/d-GalN): (1) histopathological results and MPO activities, with the activities of AST and ALT in serum, consistently demonstrated LPS and d-GalN challenge could cause severe liver damage, but BML-111 could prevent pathological changes, inhibit neutrophil infiltration, and improve the hepatic function; (2) LPS/d-GalN increased TNF-α, IL-1β, COX-2, and IL-10, while decreasing TGF-β1. However, BML-111 could repress LPS/d-GalN -induced TNF-α, IL-1β and COX-2, meanwhile increasing the expression levels of TGF-β1 and IL-10; (3) LPS/d-GalN inhibited the activities of superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (T-AOC), and hydroxyl radical-scavenging ability, simultaneously increasing the levels of MDA and NO, so also the activity of iNOS. Otherwise, BML-111 could reverse all the phenomena. In a word, BML-111 played a protective role in acute liver injury induced by LPS and d-GalN in rats, through improving antioxidant capacity and regulating the balance of inflammatory cytokines.
authors.affiliation: Department of Pharmacology, Medical College of Nanchang University, Nanchang 330006, China. yandan177@sina.com.|Department of Pharmacy, Jiangxi Province Cancer Hospital, Nanchang 330006, China. yandan177@sina.com.
authors.forename: Dan
authors.initials: D
authors.lastname: Yan
authors.affiliation: Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China. liuhailing2016@sina.com.
authors.forename: Hai-Ling
authors.initials: HL
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, Medical College of Nanchang University, Nanchang 330006, China. yuzhongjian0701@yahoo.com.|Department of Science and Education, Jiangxi Province Cancer Hospital, Nanchang 330006, China. yuzhongjian0701@yahoo.com.
authors.forename: Zhong-Jian
authors.initials: ZJ
authors.lastname: Yu
authors.affiliation: Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China. yhhuang0710@ncu.edu.cn.|Jiangxi Province Key Laboratory of Tumor Etiology and Molecular Pathology, Nanchang 330006, China. yhhuang0710@ncu.edu.cn.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Huang
authors.affiliation: Department of Human Parasitology, Medical College of Nanchang University, Nanchang 330006, China. gaodian@ncu.edu.cn.
authors.forename: Dian
authors.initials: D
authors.lastname: Gao
authors.affiliation: Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. haohua410@126.com.
authors.forename: Hua
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Pathology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China. liaoshousheng@sina.com.
authors.forename: Shou-Sheng
authors.initials: SS
authors.lastname: Liao
authors.affiliation: Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China. scbxu999@sina.com.
authors.forename: Fang-Yun
authors.initials: FY
authors.lastname: Xu
authors.affiliation: Department of Pathophysiology, Medical College of Nanchang University, Nanchang 330006, China. zhouxiaoyan@ncu.edu.cn.|Jiangxi Province Key Laboratory of Tumor Etiology and Molecular Pathology, Nanchang 330006, China. zhouxiaoyan@ncu.edu.cn.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Zhou
mesh_terms: D000208:Acute Disease; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D015153:Blotting, Western; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D005688:Galactosamine / Q000633:toxicity*; D006538:Heptanoic Acids / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D020011:Protective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C530770:5(S),6(R)-7-trihydroxyheptanoic acid, methyl ester; D000975:Antioxidants; D016207:Cytokines; D006538:Heptanoic Acids; D008070:Lipopolysaccharides; D020011:Protective Agents; D005688:Galactosamine
keywords: antioxdation; inflammation; lipoxins; liver injury