Roles of Fas/Fasl, Bcl-2/Bax, and Caspase-8 in rat nonalcoholic fatty liver disease pathogenesis

Abstract

ABSTRACT. The aim of this study was to investigate the roles of Fas/ FasL, Bcl-2/Bax, and Caspase-8 mRNA expressions in nonalcoholic fatty liver disease (NAFLD). The apoptosis percentage was measured by flow cytometry, the immunohistochemical assay was performed for the determination of Fas, FasL, Bcl-2, and Bax expressions, and a real-time polymerase chain reaction (PCR) assay was performed to detect Caspase-8 mRNA expression. Flow cytometry showed that the apoptosis percentage of the rat liver in the experimental group increased, which increased more obviously with the extension of modeling time. Immunohistochemistry showed that with increasing hepatic steatosis, Fas and FasL protein staining intensified and the number of positive cells increased; the number of positive cells for Bcl-2 and Bax gradually increased on the 4th, 8th, and 12th weeks in the experimental group, whereas the Bcl-2/Bax ratio decreased. The real-time PCR assay showed that Caspase-8 mRNA expression increased with increasing hepatic steatosis and inflammation, exhibiting a progressively rising trend. Hepatocyte apoptosis could promote NAFLD progression; Fas, FasL, and Caspase-8 mRNA activation were important contributing factors to NAFLD. The upregulation of Bax and Bcl-2 expression might be one important mechanism of the apoptosis in NAFLD.

Pathological alterations in liver injury following congestive heart failure induced by volume overload in rats

“…Here, we provide first morphological evidence of the overexpression of the proapoptotic protein Bax in hepatocytes of rats following congestive heart failure. These findings are in agreement with the previous demonstration of Bax overexpression-accompanied apoptosis in response to liver injury induced by acetaminophen [ 40 ], liver cancer [ 41 ], psychoactive drug- induced hepatotoxicity [ 42 ], non-alcoholic rat liver disease [ 43 ] or chronic hepatitis [ 44 ].…”

Histopathological Changes in the Kidney following Congestive Heart Failure by Volume Overload in Rats

“…Dysfunction of one organ often leads to a deterioration of function of the other one such as the kidney [ 27 ]. Recently, the investigation of organ crosstalk in acute renal injury reported that cell death, inflammation, cytokine and chemokine overexpression, caspase-mediated apoptotic mechanisms, and oxidative stress might induce distant organ dysfunction [ 28 , 29 ]. Consistently, the progression of heart failure may contribute to gradual toxic injury to renal cells including apoptosis and consequently persistent kidney damage and functional loss [ 5 , 9 ].…”

Effects of 4-nonylphenol on oxidant/antioxidant balance system inducing hepatic steatosis in male rat

“…Bernabò et al [6] study based on amphibian reported large lipid droplets in liver histology and ultrastructure after acute exposure to NPE. There is evidence that liver apoptosis, cell proliferation, and related genes, Fas/FasL, Bax/Bcl-2, and Caspase-8 play an important role in the genesis and development of NASH [26] . However, currently there is a paucity of information about the action and mechanism of 4-NP induced hepatic steatosis in rats.…”