Anti-Apoptotic Effects of 3,3 ',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats

Rolando Rebolledo Acevedo, Anne C. Van Erp, Petra J. Ottens, Jantje Wiersema-Buist, Henri G. D. Leuvenink*, Pamela Romanque

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

8 Citations (Scopus)
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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 (T-3). T-3 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 T-3 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. T-3 (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 T-3 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-1 beta) or the presence of pro-mitotic markers (Cyclin-D and Ki-67) were found in brain-dead animals treated with T-3 compared to vehicle-treated animals.

Conclusion

T-3 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 T-3 hormone therapy in the management of brain-dead donors.

Original languageEnglish
Article numbere0138749
Number of pages14
JournalPLoS ONE
Volume10
Issue number10
DOIs
Publication statusPublished - 5-Oct-2015

Keywords

  • POTENTIAL ORGAN DONORS
  • THYROID-HORMONE THERAPY
  • ISCHEMIA-REPERFUSION
  • PARTIAL-HEPATECTOMY
  • CLINICAL-TRIALS
  • KI-67 PROTEIN
  • MANAGEMENT
  • INJURY
  • TRANSPLANTATION
  • RESPONSES

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