Unit:
Faculty of MedicineLibrary of the School of Health Sciences
Author:
Angelis Apostolos
Dissertation committee:
Βαγιανός Κωνσταντίνος, τ. Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κουράκλης Γρηγόριος, Ομότιμος Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Καρατζάς Θεόδωρος, τ. Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Νικητέας Νικόλαος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Δημητρούλης Δημήτριος, Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Τσουρούφλης Γεράσιμος, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Κύκαλος Στυλιανός, Αναπληρωτής Καθηγητής, Ιατρική Σχολή, ΕΚΠΑ
Original Title:
Χρονική κατανομή οξειδωτικών μεταβολών του εντερικού βλεννογόνου σε αποφρακτικό ίκτερο. Επίπτωση στον εντερικό φραγμό
Translated title:
Temporal distribution of intestinal mucosal oxidative changes in obstructive jaundice. Impact on the intestinal barrier
Summary:
Patients with obstructive jaundice, particularly when exposed to the added stress of an invasive diagnostic or therapeutic procedure, are prone to develop septic complications and renal dysfunction leading to high rates of morbidity and mortality. Experimental and clinical studies have shown that obstructive jaundice causes a dysfunction of the intestinal mucosa and by extension the intestinal barrier, leading to endotoxemia which seems to play an important role in the development of these complications. The absence of bile alters the function of the intestinal barrier without disrupting the continuity of the epithelium. The molecular mechanisms contributing to this phenomenon have not been elucidated.
This thesis attempts to investigate the effect of experimental obstructive jaundice on the levels of oxidative stress in the intestinal mucosa over time. Previous studies have shown that the absence of intraluminal bile deprives the intestinal mucosa of its bacteriostatic, anti-endotoxin and trophic properties, leading to increased intraluminal bacteria and endotoxin and intestinal atrophy. These changes promote the movement of bacteria and endotoxins into the portal vein and subsequently, through a suppressed clearance capacity of Kupffer cells, due to cholestasis, into the systemic circulation. The results of the present study confirmed that obstructive jaundice led to an increase in oxidative stress in the intestine, as evidenced by an increase in lipid (PrMDA) and protein (PrC=O) peroxidation. For the oxidation of lipids the maximum value reaches 7 days and for proteins 14 days, because as more stable structures it takes more time for the oxygen metabolites to act on them. Endotoxemia and elevated bile salt concentrations are important stimulators of the production of reactive oxygen metabolites. The presence of oxidative stress in the gut contributes to the promotion of the apoptotic process and the inhibition of cell proliferation in the crypts, leading to mucosal atrophy.
In conclusion, the results of the present study show that oxidative stress increases in obstructive jaundice over time in a specific time period. In any case, further studies are needed to clarify the mechanisms of action and the possible use of antioxidant substances to reverse the effect of oxidative stress on the intestinal mucosa before the further inclusion of these parameters in clinical practice.
Main subject category:
Health Sciences
Keywords:
Oxidative stress, Enteric mucosa, Intestinal barrier, Obstructive jaundice
Number of references:
325
