Endoplasmic reticulum stress in the development of acute liver injury induced by CCl_4 in rats

Objective To investigate endoplasmic reticulum(ER) stress in the development of acute liver injury induced by carbon tetrachloride(CCl4) in rats.Methods Male Sprague-Dawley rats were randomly allocated to establish acute liver injury models by the administration of CCl4 intraperitoneally(i.p).The expression of GRP78 and caspase-12 in the liver of CCl4-treated rats were determined by Western blot analysis at different time.Serum ALT,AST and liver MDA concentration and SOD activity as well as caspase-3 activity were analyzed following CCl4 injection.Hepatocyte apoptosis was detected by TUNEL method and damage of liver was examined by histopathological means.Results It was shown that administration of CCl4 to rats caused a marked hepatic damage,characterized by significant elevation of serum ALT,AST levels and liver MDA content,caspase-3 activity combined with a remarkable reduction in liver SOD activity when compared with the control group.Histopathological observations revealed severe damage such as necrosis,fibrosis,haemorrhage,fatty degeneration.Massive hepatocyte apoptosis took place in the liver of rats following CCl4 treatment.The expression of GRP78 increased significantly from 6 to 36 hours after CCl4 administration while the expression of procaspase-12 decreased markedly at the same time.Conclusion The changes of GRP78 and caspase-12 expression in rats suggested that endoplasmic reticulum stress occurred as a result of CCl4 administration.Hepatocyte apoptosis mediated by endoplasmic reticulum stress might play an important role in the development of acute liver injury caused by CCl4.