EGF-GH Axis in Rat Steatotic and Non-steatotic Liver Transplantation From Brain-dead Donors
| Autor: | Ana I. Álvarez-Mercado, Jordi Gracia-Sancho, Esther Bujaldon, Carmen A. Peralta, Floriana Rotondo, Mónica B. Jiménez-Castro, Araní Casillas-Ramírez, José Gulfo, Cindy G. Avalos de León, Elsa Negrete-Sánchez, María Eugenia Cornide-Petronio |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Brain Death medicine.medical_specialty Time Factors medicine.medical_treatment 030230 surgery 03 medical and health sciences 0302 clinical medicine Anterior pituitary Epidermal growth factor Internal medicine medicine Animals Transplantation Epidermal Growth Factor business.industry Growth hormone secretion Liver Transplantation Rats Zucker Fatty Liver Endocrinology medicine.anatomical_structure Somatostatin Cytokine Liver Growth Hormone 030211 gastroenterology & hepatology Ghrelin business Hormone |
| Zdroj: | Transplantation. 103:1349-1359 |
| ISSN: | 0041-1337 |
| DOI: | 10.1097/tp.0000000000002636 |
| Popis: | Background We evaluated the potential dysfunction caused by changes in growth hormone (GH) levels after brain death (BD), and the effects of modulating GH through exogenous epidermal growth factor (EGF) in steatotic and nonsteatotic grafts. Methods Steatotic and nonsteatotic grafts from non-BD and BD rat donors were cold stored for 6 hours and transplanted to live rats. Administration of GH and EGF and their underlying mechanisms were characterized in recipients of steatotic and nonsteatotic grafts from BD donors maintained normotensive during the 6 hours before donation. Circulating and hepatic GH and EGF levels, hepatic damage, and regeneration parameters were evaluated. Recipient survival was monitored for 14 days. Somatostatin, ghrelin, and GH-releasing hormones that regulate GH secretion from the anterior pituitary were determined. The survival signaling pathway phosphoinositide-3-kinase/protein kinase B that regulates inflammation (suppressors of cytokine signaling, high-mobility group protein B1, oxidative stress, and neutrophil accumulation) was evaluated. Results BD reduced circulating GH and increased GH levels only in steatotic livers. GH administration exacerbated adverse BD-associated effects in both types of graft. Exogenous EGF reduced GH in steatotic livers, thus activating cell proliferation and survival signaling pathways, ultimately reducing injury and inflammation. However, EGF increased GH in nonsteatotic grafts, which exacerbated damage. The benefits of EGF for steatotic grafts were associated with increased levels of somatostatin, a GH inhibitor, whereas the deleterious effect on nonsteatotic grafts was exerted through increased amounts of ghrelin, a GH stimulator. Conclusions GH treatment is not appropriate in rat liver transplant from BD donors, whereas EGF (throughout GH inhibition) protects only in steatotic grafts. |
| Databáze: | OpenAIRE |
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