Related Experiment Video
Updated: Apr 1, 2026
Brain Death Induction in Mice Using Intra-Arterial Blood Pressure Monitoring and Ventilation via Tracheostomy
Published on: April 17, 2020
Anti-Apoptotic Effects of 3,3',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats
Rolando A Rebolledo1, Anne C Van Erp2, Petra J Ottens2
1Department of Surgery, University Medical Center Groningen, Groningen, The Netherlands; Physiopathology Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
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.
Conclusion:
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.
Insights
Thyroid hormone (T3) pre-conditioning reduced liver injury and apoptosis in brain-dead rats. This supports T3 therapy for managing brain-dead organ donors, improving organ viability.
Area of Science:
- Hepatology
- Endocrinology
- Transplantation Research
Background:
- Thyroid hormone (T3) therapy in brain-dead organ donors is debated due to variable success and unclear mechanisms.
- T3 pre-conditioning shows anti-apoptotic and pro-mitotic effects in liver ischemia/reperfusion injury models.
Purpose of the Study:
- To investigate the protective effects of T3 pre-conditioning on liver tissue in a rat model of brain death.
- To elucidate the mechanistic pathways involved in T3's therapeutic actions in brain-dead livers.
Main Methods:
- Brain death (BD) was induced in rats, followed by intraperitoneal administration of T3 or vehicle.
- Liver tissue and serum were collected after 4 hours of BD for analysis.
- RT-qPCR, biochemistry, and immunohistochemistry were employed to assess cellular injury, apoptosis, and inflammation.
Main Results:
- T3 treatment significantly lowered plasma AST and ALT levels in brain-dead rats.
- Reduced Bax gene expression and hepatic cleaved Caspase-3 activation indicated decreased apoptosis.
- No significant changes were observed in inflammatory gene expression or pro-mitotic markers.
Conclusions:
- T3 pre-conditioning confers hepatoprotective effects in brain-dead rats by reducing cellular injury and apoptosis.
- These findings support the potential clinical application of T3 hormone therapy in brain-dead organ donor management.
- T3's benefits appear primarily linked to anti-apoptotic mechanisms rather than anti-inflammatory or pro-mitotic effects in this model.
