title: Sympathetic Nervous System Control of Carbon Tetrachloride-Induced Oxidative Stress in Liver through α-Adrenergic Signaling.
abstract: In addition to being the primary organ involved in redox cycling, the liver is one of the most highly innervated tissues in mammals. The interaction between hepatocytes and sympathetic, parasympathetic, and peptidergic nerve fibers through a variety of neurotransmitters and signaling pathways is recognized as being important in the regulation of hepatocyte function, liver regeneration, and hepatic fibrosis. However, less is known regarding the role of the sympathetic nervous system (SNS) in modulating the hepatic response to oxidative stress. Our aim was to investigate the role of the SNS in healthy and oxidatively stressed liver parenchyma. Mice treated with 6-hydroxydopamine hydrobromide were used to realize chemical sympathectomy. Carbon tetrachloride (CCl4) injection was used to induce oxidative liver injury. Sympathectomized animals were protected from CCl4 induced hepatic lipid peroxidation-mediated cytotoxicity and genotoxicity as assessed by 4-hydroxy-2-nonenal levels, morphological features of cell damage, and DNA oxidative damage. Furthermore, sympathectomy modulated hepatic inflammatory response induced by CCl4-mediated lipid peroxidation. CCl4 induced lipid peroxidation and hepatotoxicity were suppressed by administration of an α-adrenergic antagonist. We conclude that the SNS provides a permissive microenvironment for hepatic oxidative stress indicating the possibility that targeting the hepatic α-adrenergic signaling could be a viable strategy for improving outcomes in patients with acute hepatic injury.
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center and Department of Pathology, Tri-Service General Hospital, 325 Section 2, Cheng-gong Road, Neihu, Taipei 114, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Jung-Chun
authors.initials: JC
authors.lastname: Lin
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center and Department of Pathology, Tri-Service General Hospital, 325 Section 2, Cheng-gong Road, Neihu, Taipei 114, Taiwan; Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Yi-Jen
authors.initials: YJ
authors.lastname: Peng
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Road, Zuoying District, Kaohsiung 81362, Taiwan.
authors.forename: Shih-Yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Mei-Ju
authors.identifier: 0000-0001-9654-2995
authors.initials: MJ
authors.lastname: Lai
authors.affiliation: Division of Gastroenterology, Department of Internal Medicine, Cardinal Tien Hospital, Fu Jen Catholic University, Taipei, Taiwan.
authors.forename: Ton-Ho
authors.initials: TH
authors.lastname: Young
authors.affiliation: Center for Molecular Medicine, MRC IGMM, University of Edinburgh, Edinburgh, UK.
authors.forename: Donald M
authors.initials: DM
authors.lastname: Salter
authors.affiliation: Graduate Institute of Medical Sciences, National Defense Medical Center and Department of Pathology, Tri-Service General Hospital, 325 Section 2, Cheng-gong Road, Neihu, Taipei 114, Taiwan; Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Road, Zuoying District, Kaohsiung 81362, Taiwan.
authors.forename: Herng-Sheng
authors.initials: HS
authors.lastname: Lee
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D015415:Biomarkers / Q000378:metabolism; D002251:Carbon Tetrachloride; D002467:Cell Nucleus / Q000187:drug effects / Q000473:pathology; D048430:Cell Shape / Q000187:drug effects; D018925:Chemokines / Q000378:metabolism; D004249:DNA Damage; D022781:Hepatocytes / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D015227:Lipid Peroxidation / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008810:Mice, Inbred C57BL; D018696:Neuroprotective Agents / Q000494:pharmacology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D016627:Oxidopamine; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D015398:Signal Transduction; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000473:pathology*
chemical_list: D000975:Antioxidants; D015415:Biomarkers; D018925:Chemokines; D018696:Neuroprotective Agents; D011942:Receptors, Adrenergic, alpha; D016627:Oxidopamine; D002251:Carbon Tetrachloride