Increased Liver Cell Steatosis and Apoptosis Represent a Mechanism towards Increased Liver Injury in Experimental Liver Fibrosis
C Kalogeropoulou, I Tsota, P Zabakis, V Tzelepi, T Petsas, D Kardamakis, A Tsamandas. University of Patras School of Medicine, Patras, Greece
Background: Liver cell steatosis seems to have a generally benign prognosis, either because most hepatocytes are not significantly damaged, or mechanisms that replace injured hepatocytes are induced. Apoptosis has been linked to liver cell depletion and ensuing liver fibrosis. This study assesses the effect of liver cell steatosis and apoptosis on the disease severity, in experimental liver fibrosis.
Design: The study comprised 54 male Wistar rats divided in 2 groups: A (n=6) controls and B (n=48): CCl4 injection (intraperitoneally 2ml/kg/BW-1:1 vol in corn oil twice weekly). In group B rats were sacrificed at 4, 8, 12 weeks. SGPT values were measured in blood samples. Steatosis (% of hepatocytes affected) was graded as follows: 0 (<5%), 1 (5%-30%), 2 (31%-70%), 3 (>70%). Liver tissues were evaluated for I) Bax, Bcl-2, TNF, and active caspase-3 mRNA (RT-PCR) and protein (Western blot), II) liver stellate cell activation (immunostain for SMA) and III) apoptosis (TUNEL method). Results were expressed following computerized analysis.
Results: Rats of groups B displayed higher SGPT values compared to controls (p<0.001). In group B, a direct correlation between liver cell apoptosis and degree of steatosis was recorded (r =0.58, p <0.01). Increased steatosis was associated with: I) decreased Bcl-2 mRNA levels (r =-0.34 p<0.05), II) increased Bax/Bcl-2 mRNA and protein ratio (r=0.63 and 0.74 p<0.01), III) active caspase-3 (r=0.64, p<0.01). In addition, a direct correlation was revealed between I) apoptosis and stellate cell activation (r =0.46, p<0.05) and II) TNF levels and active caspase-3 (r=0.68, p<0.01).
Conclusions: In cases of experimental liver fibrosis, liver cell steatosis may contribute to hepatocytic injury. Further research is warranted in order to clarify the molecular pathways responsible for the proapoptotic effect of steatosis and whether this increase in apoptosis contributes directly to progression of liver injury in cases of liver cirrhosis.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 158, Tuesday Morning