Apoptosis and Bcl‐2 Protein Expression in Experimental Alcoholic Liver Disease in the Rat

Abstract

We used the intragastric feeding rat model to investigate the relationship between severity of alcoholic liver injury, apoptosis, bcl-2 protein expression, and lipid peroxidation. Rats were fed ethanol with different dietary fats (saturated fat, corn oil, and fish oil) for a 1-month period. Apoptosis was evaluated using an immunohistochemical method, and flow cytometry. Bcl-2 protein concentrations in liver were evaluated by Western blot analysis and lipid peroxidation by measurement of conjugated dienes. Pathological changes (fatty liver, necrosis, and inflammation) were present in corn oil-ethanol and fish oil-ethanol groups only. The highest number of apoptotic cells were seen in the group of rats exhibiting liver injury. The fish oil-ethanol-fed group had the highest concentrations of bcl-2 protein; this protein was localized in the bile duct epithelial and inflammatory cells. A significant correlation was seen between bcl-2 protein assessed densitometrically and the number of inflammatory cells/mm2 (r = 0.78, p < 0.02) and conjugated diene levels (r = 0.82, p < 0.01). Increased numbers of apoptotic cells were seen in rats developing ethanol-induced pathological liver injury. Increased bcl-2 protein concentration are associated with the presence of inflammatory cells and lipid peroxidation.

Ethanol‐Induced Apoptosis in Polarized Hepatic Cells Possibly Through Regulation of the Fas Pathway

“…There is an increasing amount of evidence indicating that ethanol administration results in hepatocyte apoptosis, which may play a significant role in clinically observed manifestations of alcohol-induced liver injury (Goldin et al, 1993;Nanji, 1998;Yacoub et al, 1995;Zhao et al, 1997). Consistent with these findings, the work presented in this article clearly demonstrates that ethanol administration can cause hepatocellular damage in the form of apoptotic cell death in cultured hepatic cells.…”

“…Recently, it has been documented that ALD is associated with an increase in cellular death, particularly by an apoptotic or a programmed mechanism, and that this mode of cellular injury may play a significant role in the progression of alcohol-induced liver damage. Particularly, it has been noted that hepatocyte death via apoptosis is associated with alcohol consumption in a variety of species including humans (Benedetti et al, 1988;Goldin et al, 1993;Natori et al, 2001) and that the number of apoptotic cells detected in the liver correlates with the development of ethanol-induced liver injury Yacoub et al, 1995).…”

Paraoxonase-1 is associated with oxidative stress, fibrosis and FAS expression in chronic liver diseases

“…Particularly, this has been reported in hepatitis C infection, alcoholic liver disease, non alcoholic steatohepatitis, and acute liver failure [4][5][6]. The apoptotic process is characterized by a complete and active destruction of cellular proteins and DNA produced by a group of proteases, called caspases [7].…”

The protective efficacy of vitamins (C and E), selenium and silymarin supplements against alcohol toxicity

“…Studies in mice and rats revealed that both acute and chronic alcohol administration resulted in significant increases in hepatocyte apoptosis (Goldin et al, 1993, Yacoub et al, 1995. Potential mechanisms of acute ethanolinduced liver apoptosis include increased cytokine activity, Fas ligand (FasL) expression, and/or oxidative stress (Kurose et al, 1997, Neuman et al, 2001.…”