Unit:
Τομέας ΧειρουργικήςLibrary of the School of Health Sciences
Author:
Zavridis Periklis
Dissertation committee:
Λέανδρος Εμμανουήλ, Καθηγητής, Ιατρική, ΕΚΠΑ
Ζωγράφος Γεώργιος, Καθηγητής, Ιατρική, ΕΚΠΑ
Μενενάκος Ευάγγελος, Αναπληρωτής Καθηγητή, Ιατρική, ΕΚΠΑ
Τούτουζας Κωνσταντίνος του Γεωργίου, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Αλεξάκης Νικόλαος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Ζαγούρη Φλώρα, Αναπληρώτρια Καθηγήτρια, Ιατρική, ΕΚΠΑ
Παπαλόης Απόστολος, Αναπληρωτής Καθηγητής, Ιατρική, ΕΚΠΑ
Original Title:
Πειραματικό πρότυπο ηπατεκτομής σε χοίρους. Μελέτη δράσης του αντιοξειδωτικού μορίου U-74389G (21 – AMINOSTEROID) σε δείκτες φλεγμονώδους απάντησης
Translated title:
U-74389G significantly reduced TNF-a in a swine model of acute liver ischemia-reperfusion injury
Summary:
Introduction: Ischemia and reperfusion of liver during hepatic surgery and trauma has been associated with a wide variety of pathophysiological changes resulting to hepatic dysfunction and increased postoperative morbidity. Ischemia reperfusion injury (IRI) is a complication that occurs when blood flow is restricted to an organ followed by reflow, which leads to alterations in the physiology of the organ through a complicated mechanism that includes microvascular injury, increased production of reactive oxygen species from activated endothelial cells, inflammatory response during which white blood cells bind to the endothelium of capillaries obstructing them and inflammatory factors such as interleukins and free radicals are produced in response to tissue damage, and increased apoptosis. Among the pharmacological interventions to reduce IRI in various organs are lazaroids, a group of synthetic aminosteroids with no glucocorticoid action that inhibit iron-dependent lipid peroxidation
Aim: The aim of this study was to determine whether intraoperative administration of the lazaroid U-74389G can reduce inflammatory activity in landrace pigs undergoing hepatectomy with Pringle maneuver.
Methods: Fourteen landrace pigs (30 ± 2 Kgr) were randomized into two groups: in group A (n =7) lazaroid U-74389G was administrated immediately after the Pringle maneuver was removed while in group B (control group, n= 7) it was not. Blood samples were obtained at four phases: 1) before clamping 2) 30 minute after clamping removal and beginning of reperfusion 3) two hours after hepatectomy and 4) 24 hours after hepatectomy. Quantitative analyses of the inflammatory markers IL-1β, IL-10, IFN-α, IFN-γ, TNF-α, IL-4, and IL-8 were performed. In order to histopathologically evaluate the number of neutrophils, lymphocytes, macrophages and apoptotic bodies in liver in the two groups, samples which included at least one big vessel were taken at phases 3 and 4.
Results: Histological analysis revealed the presence of inflammation and apoptosis, of the same density, in both groups. Biochemical analysis revealed a statistically significant decrease (P <0.01) of TNF-α at phases 2, 3 and 4 and of IFN-α (p = 0.02) at phase 4 in group A compared to control group.
Conclusion: Pro-apoptotic chemokine TNFα was significantly reduced for 24 hours after the administration of antioxidant U-74389G in group A while IFN-α was significantly reduced at phase 4 in group A . However, the effect of U-74389G did not appear to be obvious in terms of inflammation and apoptosis in histological evaluation. Based on the results from the serum levels of TNF-α and IFN-α in blood serum of the treated experimental animals we can possibly conclude that the lazaroid U-74389G could have a positive effect on liver IRI which is reflected by the lower levels of these specific cytokines.
Main subject category:
Health Sciences
Keywords:
Lazaroid, U-74389G, Liver, Swine, Reperfusion, TNF-α
Number of references:
121
