title: Activation of α2 adrenoceptor attenuates lipopolysaccharide-induced hepatic injury.
abstract: Sepsis induces hepatic injury but whether alpha-2 adrenoceptor (α2-AR) modulates the severity of sepsis-induced liver damage remains unclear. The present study used lipopolysaccharide (LPS) to induce hepatic injury and applied α2-AR agonist dexmedetomidine (DEX) and/or antagonist yohimbine to investigate the contribution of α2-AR in LPS-induced liver injury. Our results showed that LPS resulted in histological and functional abnormality of liver tissue (ALT and AST transaminases, lactate), higher mortality, an increase in proinflammatory cytokines (IL-1β, IL-6 & TNF-α), as well as a change in oxidative stress (MDA, SOD). Activation of α2-AR by dexmedetomidine (DEX) attenuated LPS-induced deleterious effects on the liver and block of α2-AR by yohimbine aggravated LPS-induced liver damage. Our data suggest that α2-AR plays an important role in sepsis-induced liver damage and activation of α2-AR with DEX could be a novel therapeutic avenue to protect the liver against sepsis-induced injury.
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510630, People's Republic of China.
authors.forename: Jing-Hui
authors.initials: JH
authors.lastname: Chen
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510630, People's Republic of China.
authors.forename: Gao-Feng
authors.initials: GF
authors.lastname: Yu
authors.affiliation: Department of Cardiovascular, The Third Affiliated Hospital, Sun Yat-Sen University Guangzhou 510630, People's Republic of China.
authors.forename: Shang-Yi
authors.initials: SY
authors.lastname: Jin
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510630, People's Republic of China.
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510630, People's Republic of China.
authors.forename: Dong-Xu
authors.initials: DX
authors.lastname: Lei
authors.affiliation: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-Sen University Guangzhou 510630, People's Republic of China.
authors.forename: Shao-Li
authors.initials: SL
authors.lastname: Zhou
authors.affiliation: Department of Anesthesiology, Guangzhou Women and Children's Medical Center, Guangzhou Medical University Guangzhou 510630, People's Republic of China.
authors.forename: Xing-Rong
authors.initials: XR
authors.lastname: Song
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000494:pharmacology*; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D056486:Chemical and Drug Induced Liver Injury / Q000097:blood / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D019610:Cytoprotection; D020927:Dexmedetomidine / Q000494:pharmacology*; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D008070:Lipopolysaccharides; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000378:metabolism; D018805:Sepsis / Q000139:chemically induced; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015016:Yohimbine / Q000494:pharmacology
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D015415:Biomarkers; C000594089:IL1B protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D018343:Receptors, Adrenergic, beta-2; D014409:Tumor Necrosis Factor-alpha; C440499:lipopolysaccharide, Escherichia coli O111 B4; D015016:Yohimbine; D019344:Lactic Acid; D008315:Malondialdehyde; D020927:Dexmedetomidine; D013482:Superoxide Dismutase; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase
keywords: Sepsis; dexmedetomidine; liver injury; yohimbine; α2-adrenoceptor agonist