title: The role of alpha-1 and alpha-2 adrenoceptors in restraint stress-induced liver injury in mice.
abstract: Acute stress affects cellular integrity in many tissues including the liver, but its underlying mechanism is still unclear. The aim of the present study was to investigate the potential involvement of catecholamines and adrenoceptors in the regulation of acute restraint stress-induced liver injury. Restraint was achieved by placing mice in restraint tubes. Mice were treated with either an α-l antagonist, prazosin, an α-2 antagonist, yohimbine, a β-l antagonist, betaxolol, a β-2 antagonist, ICI 118551, or a central and peripheral catecholamine depleting agent, reserpine, and followed by restraint stress. Assessment of liver injury (serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) , hepatic total GSH, GSSG and GSH/GSSG ratio) , histopathology and of apoptosis, by TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling) assay and western blotting, was performed. Three hours of restraint stress resulted in liver injury, as indexed by elevated serum transaminase levels, decreased hepatic total GSH levels and GSH/GSSG ratio, increased hepatic GSSG levels as well as enhanced hepatocytes apoptosis. Either reserpine or prazosin or yohimbine was found to attenuate liver injury. Furthermore, prazosin and yohimbine protected against restraint-induced hepatocytes apoptosis through attenuating the activation of caspases-9 and -3 and reducing the Bax/Bcl-2 ratio. These results suggest that α-1 and α-2 adrenoceptors mediate restraint-induced liver oxidative injury through caspase-9 and Bcl-2 family of apoptotic regulatory proteins.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China; Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Qinghaosu (Artemisinin) Research Center, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China.
authors.forename: Liwei
authors.initials: L
authors.lastname: Gu
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Yimei
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jia
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Zengming
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Evaluation and Research Center for Toxicology, Institute of Disease Control and Prevention, Academy of Military Medical Sciences, Beijing, China.
authors.forename: Shuangqing
authors.initials: S
authors.lastname: Peng
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, China.
authors.forename: Linsheng
authors.initials: L
authors.lastname: Lei
mesh_terms: D058668:Adrenergic alpha-1 Receptor Antagonists / Q000494:pharmacology; D058669:Adrenergic alpha-2 Receptor Antagonists / Q000494:pharmacology; D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001219:Aspartate Aminotransferases / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D020287:In Situ Nick-End Labeling / Q000379:methods; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008107:Liver Diseases / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D020011:Protective Agents / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism*
chemical_list: D058668:Adrenergic alpha-1 Receptor Antagonists; D058669:Adrenergic alpha-2 Receptor Antagonists; D020011:Protective Agents; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D053148:Caspase 3; D053453:Caspase 9; D005978:Glutathione; D019803:Glutathione Disulfide