Dissertation committee:
Ζάβρας Νικόλαος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή,
Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Αναστάσιος Μαχαίρας, Καθηγητής, Ιατρική Σχολή, Εθνικό και
Καποδιστριακό Πανεπιστήμιο Αθηνών.
Παύλος Πατάπης, Καθηγητής, Ιατρική Σχολή, Εθνικό και Καποδιστριακό
Πανεπιστήμιο Αθηνών.
Εμμανουήλ Πικουλής, Καθηγητής, Ιατρική Σχολή, Εθνικό και
Καποδιστριακό Πανεπιστήμιο Αθηνών.
Ευάγγελος Μισιακός, Καθηγητής, Ιατρική Σχολή, Εθνικό και
Καποδιστριακό Πανεπιστήμιο Αθηνών.
Ανέστης Χαραλαμπόπουλος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή,
Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών.
Κωνσταντίνος Νάστος, Επίκουρος Καθηγητής, Ιατρική Σχολή, Εθνικό
και Καποδιστριακό Πανεπιστήμιο Αθηνών.
Summary:
Introduction: Hepatic regeneration is a complex process involving a multitude of well-timed molecular operations. Ursodeoxycholic acid (UDCA) is postulated to exert a protective effect against oxidative stress and enzymatic degradation of the extracellular matrix, in turn potentiating the regenerative response. The aim of the present animal study is to evaluate the impact of UDCA administration in liver tissue expression of cyclooxygenase-2 (COX-2) in a setting of acute liver failure achieved by extended (80%) hepatectomy.
Materials and methods: Twenty-four adult male Sprague-Dawley rats were randomly assigned to an experimental (UDCA) and a control group. Animals in the UDCA received oral pretreatment with UDCA for 14 days, while animals in the control group received saline. All animals underwent resection of approximately 80% of the liver parenchyma. Tissue and blood sample collection were performed 48 hours postoperatively.
Results: The postoperative mitotic index and Ki-67 levels were found to be elevated in the UDCA group (43±11.4 and 13.7±24.7 versus 31±16.7 and 7.6±5.7), albeit without any statistical significance. Pretreatment with UDCA significantly decreased COX-2 expression levels (p=0.028) as well as serum tumor necrosis factor α (TNFα) levels (37.3±10.9 pg/mL versus 75.4±14.4 pg/mL, p=0.004). COX-2 expression score was observed to be weakly correlated to Ki-67 levels in both groups. Although COX-2 expression score was not correlated with serum TNFα levels in the control group, animals pretreated with UDCA exhibited moderate correlation (r=0.45).
Conclusion: Preoperative administration of UDCA exerts a suppressive effect on tissue expression of COX-2 following 80% hepatectomy and enforces a positive correlation between COX-2 and serum TNFα levels, suggesting that UDCA preconditions liver tissue to display an enhanced regenerative response to circulating cytokines, most notably TNFα. The weak association of COX-2 with Ki-67 expression levels suggests that COX-2 may be of secondary importance during the early phases of liver regeneration.
Keywords:
Liver regeneration, Hepatectomy, COX-2, TNFα
