The effect of cortisol in rat steatotic and non-steatotic liver transplantation from brain-dead donors

2017 ◽  
Vol 131 (8) ◽  
pp. 733-746 ◽  
Author(s):  
Mónica B. Jiménez-Castro ◽  
Elsa Negrete-Sánchez ◽  
Araní Casillas-Ramírez ◽  
Jose Gulfo ◽  
Ana I. Álvarez-Mercado ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Liver Graft ◽  
Steatotic Liver ◽  
Kinase C ◽  
Protective Strategy ◽  
Brain Dead ◽  
Underlying Mechanisms ◽  
Phosphoinositide 3 Kinase ◽  
Brain Dead Donor

In the present study, we examined the effects of cortisol on steatotic and non-steatotic liver grafts from brain-dead donors and characterized the underlying mechanisms involved. Non-steatotic liver grafts showed reduced cortisol and increased cortisone levels in association with up-regulation of enzymes that inactivate cortisol. Conversely, steatotic liver grafts exhibited increased cortisol and reduced cortisone levels. The enzymes involved in cortisol generation were overexpressed, and those involved in cortisol inactivation or clearance were down-regulated in steatotic liver grafts. Exogenous administration of cortisol negatively affected hepatic damage and survival rate in non-steatotic liver transplantation (LT); however, cortisol treatment up-regulated the phosphoinositide 3-kinase (PI3K)–protein kinase C (PKC) pathway, resulting in protection against the deleterious effects of brain-dead donors on damage and inflammatory response in steatotic LT as well as in increased survival of recipients. The present study highlights the differences in the role of cortisol and hepatic mechanisms that regulate cortisol levels based on the type of liver. Our findings suggest that cortisol treatment is a feasible and highly protective strategy to reduce the adverse effects of brain-dead donor livers in order to ultimately improve liver graft quality in the presence of steatosis, whereas cortisol treatment would not be recommended for non-steatotic liver grafts.

EGF-GH Axis in Rat Steatotic and Non-steatotic Liver Transplantation From Brain-dead Donors

2019 ◽  
Vol 103 (7) ◽  
pp. 1349-1359 ◽  
Author(s):  
Ana I. Álvarez-Mercado ◽  
Elsa Negrete-Sánchez ◽  
José Gulfo ◽  
Cindy G. Ávalos de León ◽  
Araní Casillas-Ramírez ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Steatotic Liver ◽  
Brain Dead

Understanding the effect of corticosteroid pretreatment in brain-dead organ donors: new mechanistic insights for improvement of organ quality in liver transplantation

2017 ◽  
Vol 131 (18) ◽  
pp. 2377-2379
Author(s):  
Carola Dahrenmöller ◽  
Raymond Reding
Keyword(s):  
Liver Transplantation ◽  
Liver Function ◽  
Molecular Mechanisms ◽  
Organ Donors ◽  
Liver Transplants ◽  
Long Time ◽  
Organ Quality ◽  
Brain Dead ◽  
Brain Dead Donor

Transplant surgeons are currently faced with the challenge to accept marginal liver transplants due to steatosis or old age. Improving organ quality by implementing a selective organ protective donor management could be the first step towards a graft of enhanced quality. However, the molecular mechanisms of such treatments are still poorly understood. Glucocorticoid medication in donor medicine has been carried out and discussed for a long time. In a recent study published in Clinical Science, Jiménez-Castro et al. [Clin. Sci. (2017) 131, 733-746] demonstrate how liver histology and transplant liver function can be improved by administration of glucocorticoids to brain-dead donor rats with steatotic livers. This work illustrates the need for further trials in order to selectively improve the quality of steatotic livers with a potential for liver transplantation.

Platelet-activating factor induces cardioprotection in isolated rat heart akin to ischemic preconditioning: role of phosphoinositide 3-kinase and protein kinase C activation

2005 ◽  
Vol 288 (5) ◽  
pp. H2512-H2520 ◽  
Author(s):  
Claudia Penna ◽  
Giuseppe Alloatti ◽  
Sandra Cappello ◽  
Donatella Gattullo ◽  
Giovanni Berta ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Ischemic Preconditioning ◽  
Platelet Activating Factor ◽  
Left Ventricular ◽  
Isolated Rat Heart ◽  
Cardioprotective Effect ◽  
Kinase C ◽  
Phosphoinositide 3 Kinase

Ischemic preconditioning (IP) is a cardioprotective mechanism against myocellular death and cardiac dysfunction resulting from reperfusion of the ischemic heart. At present, the precise list of mediators involved in IP and the pathways of their mechanisms of action are not completely known. The aim of the present study was to investigate the role of platelet-activating factor (PAF), a phospholipid mediator that is known to be released by the ischemic-reperfused heart, as a possible endogenous agent involved in IP. Experiments were performed on Langendorff-perfused rat hearts undergoing 30 min of ischemia followed by 2 h of reperfusion. Treatment with a low concentration of PAF (2 × 10−11 M) before ischemia reduced the extension of infarct size and improved the recovery of left ventricular developed pressure during reperfusion. The cardioprotective effect of PAF was comparable to that observed in hearts in which IP was induced by three brief (3 min) periods of ischemia separated by 5-min reperfusion intervals. The PAF receptor antagonist WEB-2170 (1 × 10−9 M) abrogated the cardioprotective effect induced by both PAF and IP. The protein kinase C (PKC) inhibitor chelerythrine (5 × 10−6 M) or the phosphoinositide 3-kinase (PI3K) inhibitor LY-294002 (5 × 10−5 M) also reduced the cardioprotective effect of PAF. Western blot analysis revealed that following IP treatment or PAF infusion, the phosphorylation of PKC-ε and Akt (the downstream target of PI3K) was higher than that in control hearts. The present data indicate that exogenous applications of low quantities of PAF induce a cardioprotective effect through PI3K and PKC activation, similar to that afforded by IP. Moreover, the study suggests that endogenous release of PAF, induced by brief periods of ischemia and reperfusion, may participate to the triggering of the IP of the heart.

scholarly journals The Effect of Fibroblast Growth Factor 15 Signaling in Non-Steatotic and Steatotic Liver Transplantation from Cardiocirculatory Death

Cells ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 1640 ◽  
Author(s):  
Cindy G. Avalos-de León ◽  
Mónica B. Jiménez-Castro ◽  
María Eugenia Cornide-Petronio ◽  
José Gulfo ◽  
Floriana Rotondo ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Growth Factor ◽  
Bile Acids ◽  
Fibroblast Growth Factor ◽  
Proliferative Response ◽  
Minor Role ◽  
Fibroblast Growth ◽  
Steatotic Liver ◽  
A Minor

We elucidate the relevance of fibroblast growth factor 15 (FGF15) in liver transplantation (LT) using rats with both steatotic and non-steatotic organs from donors after cardiocirculatory death (DCD). Compared to LT from non-DCDs, the induction of cardiocirculatory death (CD) increases hepatic damage, proliferation, and intestinal and circulatory FGF15. This is associated with high levels of FGF15, bilirubin and bile acids (BAs), and overexpression of the enzyme involved in the alternative BA synthesis pathway, CYP27A1, in non-steatotic livers. Furthermore, CD activates the proliferative pathway, Hippo/YAP, in these types of liver. Blocking FGF15 action in LT from DCDs does not affect CYP27A1 but causes an overexpression of CYP7A, an enzyme from the classic BA synthesis pathway, and this is related to further accumulation of BAs and exacerbated damage. FGF15 inhibition also impairs proliferation without changing Hippo/YAP. In spite of worse damage, steatosis prevents a proliferative response in livers from DCDs. In steatotic grafts, CD does not modify CYP7A1, CYP27A1, BA, or the Hippo/YAP pathway, and FGF15 is not involved in damage or proliferation. Thus, endogenous FGF15 protects against BA accumulation and damage and promotes regeneration independently of the Hippo/YAP pathway, in non-steatotic LT from DCDs. Herein we show a minor role of FGF15 in steatotic LT from DCDs.

HMGB1 in Steatotic and Non-Steatotic Liver Transplantation from brain- Dead Donors with Previous Ischemic Preconditioning

2016 ◽  
Vol 64 (2) ◽  
pp. S316
Author(s):  
M.B. Jimenez-Castro ◽  
E. Negrete-Sanchez ◽  
C.A. de León ◽  
A. Casillas-Ramírez ◽  
M.E. Cornide-Petronio ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Ischemic Preconditioning ◽  
Steatotic Liver ◽  
Brain Dead

scholarly journals Deceased Brain Dead Donor Liver Transplantation and Utilization in the United States

2019 ◽  
Vol 103 (7) ◽  
pp. 1392-1404
Author(s):  
Dustin J. Carpenter ◽  
Mariana C. Chiles ◽  
Elizabeth C. Verna ◽  
Karim J. Halazun ◽  
Jean C. Emond ◽  
...  
Keyword(s):  
United States ◽  
Liver Transplantation ◽  
The United States ◽  
Donor Liver ◽  
Donor Liver Transplantation ◽  
Brain Dead ◽  
Brain Dead Donor

FGF15 improves outcomes after brain dead donor liver transplantation with steatotic and non-steatotic grafts in rats

2020 ◽  
Vol 73 (5) ◽  
pp. 1131-1143 ◽  
Author(s):  
José Gulfo ◽  
Floriana Rotondo ◽  
Cindy G. Ávalos de León ◽  
María Eugenia Cornide-Petronio ◽  
Carla Fuster ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Donor Liver ◽  
Donor Liver Transplantation ◽  
Brain Dead ◽  
Brain Dead Donor
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