OP 119. The Effect of Portal Vein Ligation on Drug-Metabolizing Function of the Liver


E. Háfra, A Fülöp, A. Szijártó, K. Monostory

Chair(s): Thomas van Gulik, Attila Szijártó, András Fülöp

13:50 - 14:00h at Pest Room (C)

Categories: Pathophysiology

Session: Oral Session XIII - Hepatobiliary and Pancreatic Surgery I


Background:
The portal vein ligation (PVL) induced regenerative and atrophic processes might accompany by alteration in liver drug-metabolizing function. The metabolism of xenobiotics primarily depends on the levels and activities of cytochrome P450 enzymes (CYP). The aim of this preliminary study is to evaluate the alterations in gene expression of different CYP enzymes after portal vein ligation in healthy rats’ liver.

Material and Methods:
Male Wistar rats underwent PVL. Liver samples from the ligated and non-ligated liver lobes were taken before (0) and 24, 48, 72 and 168 hours after PVL. The alteration in liver mass and the histological characteristics of liver lobes were determined. Furthermore, the mRNA levels of CYP1A1, CYP1A2, CYP2B1, CYP2B2, CYP2C6, CYP2C11, CYP2C13, CYP3A1, and CYP3A2 were quantified by real-time PCR in liver samples.

Result:
PVL induced considerable atrophy of portal deprived liver lobes (3.16 vs.0.85 g / 100g BW), while the non-ligated part of liver showed compensatory hyperplasia (0.97 vs. 3.28 g / 100g BW).The regenerative process was characterized by a significantly elevated mitotic activity of hepatocyte (21.43 vs. 139.23 / HPF), while in the ligated lobes necrotic and apoptotic cell death was typical. The regenerative and atrophic processes differently influenced the expression of the examined drug-metabolizing enzymes.

Conclusion:
PVL induced regenerative and atrophic processes affects the mRNA expression of different CYP enzymes, which alterations could considerable influence the drug-metabolizing capacity of liver until the PVL triggered liver regeneration is completed.