title: Naltrexone attenuates endoplasmic reticulum stress induced hepatic injury in mice.
abstract: Endoplasmic reticulum (ER) stress provides abnormalities in insulin action, inflammatory responses, lipoprotein B100 degradation and hepatic lipogenesis. Excess accumulation of triglyceride in hepatocytes may also lead to disorders such as non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Opioid peptides are involved in triglyceride and cholesterol dysregulation, inflammation and cell death. In this study, we evaluated Naltrexone effects on ER stress induced liver injury. To do so, C57/BL6 mice received saline, DMSO and Naltrexone, as control groups. ER stress was induced by tunicamycin (TM) injection. Naltrexone was given before TM administration. Liver blood flow and biochemical serum analysis were measured. Histopathological evaluations, TNF-α measurement and Real-time RT-PCR were also performed. TM challenge provokes steatosis, cellular ballooning and lobular inflammation which significantly reduced in Naltrexone treated animals. ALT, AST and TNF-α increased in the TM group and improved in the Naltrexone plus TM group. Triglyceride and cholesterol levels decreased in TM treated mice with no increase in Naltrexone treated animals. In the Naltrexone plus TM group, gene expression of Bax/Bcl-2 ratio and caspase3 significantly lowered compared with the TM group. In this study, we found that Naltrexone had a notable alleviating role in ER stress induced steatosis and liver injury.
authors.affiliation: Tehran University of Medical Sciences Department of Physiology, School of Medicine Tehran 1417613151 Iran.
authors.forename: A
authors.initials: A
authors.lastname: Moslehi
authors.forename: F
authors.initials: F
authors.lastname: Nabavizadeh
authors.affiliation: Tehran University of Medical Sciences Department of Physiology, School of Medicine Tehran 1417613151 Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Nabavizadeh
authors.forename: A R
authors.initials: AR
authors.lastname: Dehpour
authors.affiliation: Tehran University of Medical Sciences Department of Pharmacology, School of Medicine Tehran Iran.
authors.forename: A R
authors.initials: AR
authors.lastname: Dehpou
authors.affiliation: Tehran University of Medical Sciences Shariati Hospital Tehran Iran.
authors.forename: S M
authors.initials: SM
authors.lastname: Tavanga
authors.affiliation: Tehran University of Medical Sciences Department of Anatomy, School of Medicine Tehran Iran.
authors.forename: G
authors.initials: G
authors.lastname: Hassanzadeh
authors.affiliation: Tehran University of Medical Sciences Department of Genetics, School of Medicine Tehran Iran.
authors.forename: A
authors.initials: A
authors.lastname: Zekri
authors.affiliation: Pasteur Institute of Iran Department of Parasitology Tehran Iran.
authors.forename: H
authors.initials: H
authors.lastname: Nahrevanian
authors.affiliation: Iran University of Medical Sciences Department of Physiology, School of Medicine Tehran Iran.
authors.forename: H
authors.initials: H
authors.lastname: Sohanaki
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D001219:Aspartate Aminotransferases / Q000097:blood; D015415:Biomarkers / Q000097:blood; D053148:Caspase 3 / Q000378:metabolism; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D019610:Cytoprotection; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D005234:Fatty Liver / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D008099:Liver / Q000098:blood supply / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D065626:Non-alcoholic Fatty Liver Disease; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014415:Tunicamycin; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; C494827:Bax protein, mouse; D015415:Biomarkers; D009292:Narcotic Antagonists; D019253:Proto-Oncogene Proteins c-bcl-2; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D014415:Tunicamycin; C052617:Bcl2 protein, mouse; D009271:Naltrexone; D002784:Cholesterol; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: endoplasmic reticulum stress; liver; naltrexone; steatosis; tunicamycin