Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Dissertation committee:
Δανιάς Νικόλαος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ.
Μαχαίρας Αναστάσιος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ.
Παταπής Παύλος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ.
Πικουλής Εμμανουήλ, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ.
Κόντζογλου Κωνσταντίνος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ.
Κοντογεωργάκος Βασίλειος,Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ. (
Νάστος Κωνσταντίνος, Επίκουρος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ.
Original Title:
Η επίδραση του ουρσοδεοξυχολικού οξέος στα επίπεδα του TNF-α και της IL-6 στην ηπατική αναγέννηση σε πειραματικό μοντέλο ηπατεκτομής σε επίμυες
Translated title:
The effects of ursodeoxycholic acid pretreatment in an experimental setting of extended hepatectomy: a feasibility study
Summary:
Introduction Liver regeneration is an exceptionally complex process, orchestrated by a multitude of growth factors and cytokines. Tumor necrosis factor-alpha (TNF-a) and interleukin-6 (Il-6) have a pivotal role in the initiation of the regenerative response. Ursodeoxycholic acid (UDCA) exhibits a liver protective effect that enhances liver growth after injury. The aim of the present study is to evaluate the effect of UDCA in the circulating levels of TNF-a and Il-6 in rats undergoing extended 80% hepatectomy. Materials and methods Twenty-two male Sprague Dawley rats were randomly assigned in an experimental (UDCA group) and a control group. Mice in the UDCA-group received oral pretreatment of UDCA for two weeks preoperatively at a dosage of 25 mg/kg/day. An 80% hepatic resection was performed in both groups by resecting the middle, inferior right, and left lateral liver lobes. The experiment ended 48 hours postoperatively. Results UDCA pretreatment significantly depressed circulating levels of both TNF-a and Il-6 after the conclusion of the experiment as compared to the control group (p=0.001 and p=0.01, respectively). Furthermore, TNF-a levels were significantly reduced before the institution of liver injury (p=0.02). Mice in the UDCA-group exhibited better liver growth as demonstrated by significantly increased Ki-67 and mitotic rate (p=0.04 and p=0.02, respectively). Finally, the liver regeneration rate (LRR) was significantly elevated in the experimental group (UDCA group, 54.5% vs control group, 35.8%; p=0.002) signifying enhanced liver growth kinetics. Conclusion UDCA reduces the expression of TNF-a and Il-6 during the priming phase of liver regeneration. An 80% hepatectomy model of acute liver failure exhibited enhanced liver regeneration in the experimental group, plausibly due to the immunomodulatory effects of UDCA.
Main subject category:
Health Sciences
Keywords:
Extended hepatectomy, Liver regeneration, Liver resection, Ursodeoxycholic acid.
Number of references:
141
File:
File access is restricted only to the intranet of UoA.
PASPALA.ANNA.pdf
15 MB
File access is restricted only to the intranet of UoA.
