title: Anti-Apoptotic Effects of 3,3',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats.
abstract: BACKGROUND
  Thyroid hormone treatment in brain-dead organ donors has been extensively studied and applied in the clinical setting. However, its clinical applicability remains controversial due to a varying degree of success and a lack of mechanistic understanding about the therapeutic effects of 3,3',5-Triiodo-L-thyronine (T3). T3 pre-conditioning leads to anti-apoptotic and pro-mitotic effects in liver tissue following ischemia/reperfusion injury. Therefore, we aimed to study the effects of T3 pre-conditioning in the liver of brain-dead rats.
  
  
  METHODS
  Brain death (BD) was induced in mechanically ventilated rats by inflation of a Fogarty catheter in the epidural space. T3 (0.1 mg/kg) or vehicle was administered intraperitoneally 2 h prior to BD induction. After 4 h of BD, serum and liver tissue were collected. RT-qPCR, routine biochemistry, and immunohistochemistry were performed.
  
  
  RESULTS
  Brain-dead animals treated with T3 had lower plasma levels of AST and ALT, reduced Bax gene expression, and less hepatic cleaved Caspase-3 activation compared to brain-dead animals treated with vehicle. Interestingly, no differences in the expression of inflammatory genes (IL-6, MCP-1, IL-1β) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T3 compared to vehicle-treated animals.
  
  
  CONCLUSIONS
  T3 pre-conditioning leads to beneficial effects in the liver of brain-dead rats as seen by lower cellular injury and reduced apoptosis, and supports the suggested role of T3 hormone therapy in the management of brain-dead donors.
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Rolando A
authors.initials: RA
authors.lastname: Rebolledo
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Anne C
authors.initials: AC
authors.lastname: Van Erp
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Petra J
authors.initials: PJ
authors.lastname: Ottens
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Wiersema-Buist
authors.affiliation: Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Henri G D
authors.initials: HG
authors.lastname: Leuvenink
authors.affiliation: Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Romanque
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001926:Brain Death / Q000378:metabolism / Q000473:pathology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008938:Mitosis / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D014284:Triiodothyronine / Q000494:pharmacology*
chemical_list: D014284:Triiodothyronine