TY - JOUR
T1 - Anti-Apoptotic Effects of 3,3 ',5-Triiodo-L-Thyronine in the Liver of Brain-Dead Rats
AU - Rebolledo Acevedo, Rolando
AU - Van Erp, Anne C.
AU - Ottens, Petra J.
AU - Wiersema-Buist, Jantje
AU - Leuvenink, Henri G. D.
AU - Romanque, Pamela
PY - 2015/10/5
Y1 - 2015/10/5
N2 - BackgroundThyroid 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.MethodsBrain 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.ResultsBrain-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.ConclusionT-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.
AB - BackgroundThyroid 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.MethodsBrain 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.ResultsBrain-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.ConclusionT-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.
KW - POTENTIAL ORGAN DONORS
KW - THYROID-HORMONE THERAPY
KW - ISCHEMIA-REPERFUSION
KW - PARTIAL-HEPATECTOMY
KW - CLINICAL-TRIALS
KW - KI-67 PROTEIN
KW - MANAGEMENT
KW - INJURY
KW - TRANSPLANTATION
KW - RESPONSES
U2 - 10.1371/journal.pone.0138749
DO - 10.1371/journal.pone.0138749
M3 - Article
C2 - 26437380
SN - 1932-6203
VL - 10
JO - PLoS ONE
JF - PLoS ONE
IS - 10
M1 - e0138749
ER -