title: [Mitochondrial activities of citrate synthase, carnitine palmitoyltransferase-1 and cytochrome C oxidase are increased during the apoptotic process in hepatocytes of a rat model of acute liver failure].
abstract: OBJECTIVE
  To determine the roles of mitochondrial apoptosis and energy metabolism in hepatocytes during the pathogenic process of acute renal failure (ALF) by assessing disease-related differential activities of several key mitochondrial enzymes, including citrate synthase (CS), carnitine palmitoyltransferase-1 (CPT-1) and cytochrome c oxidase (COX).
  
  
  METHODS
  Thirty-two male Sprague Dawley rats were given D-galactosamine followed by and lipopolysaccharide (LPS) to induce acute liver failure and sacrificed after 4 (4 h group), 8 (8 h group) 12 (12 h group) and 24 hours (24 h group) of treatment. Eight unmodeled rats served as controls. Effects related to apoptosis were evaluated by pathological analysis of hepatic tissues and TUNEL staining. Ultrastructural changes in mitochondria were assessed by electron microscopy. The activity and expression of CS, CPT-1 and COX were measured.
  
  
  RESULTS
  Hepatocyte apoptosis was present in the 4 h treatment group and was increased obviously in the 8 h treatment group. Hepatocyte necrosis was first observed in the 12 h treatment group and was significantly higher in the 24 h treatment group, with inflammatory cell invasion. Ultrastructural changes in mitochondria were present in the 4 h treatment group, and the 24 h treatment group showed mitochondria with completely destroyed outer membranes, which resulted in mitochondrial collapse. Activity and protein expression of CS, CPT-1 and COX were increased in the 4 h group (vs. controls), were at their peak in the 8 h group (CS:t =1.481, P less than 0.01; CPT-1:t =2.619, P less than 0.05; COX:t =1.014, P less than 0.01) and showed a decreasing trend in the 12 h group. In addition, the activities of CS, CPT-1 and COX were enhanced at the stage of hepatocyte apoptosis, suggesting that these enzymes were involved in the initiation and development of ALF.
  
  
  CONCLUSIONS
  Energy metabolism plays an important role in hepatocyte apoptosis during ALF.
authors.affiliation: The Second Affiliated hospital of Harbin Medical University, Harbin 150001, China.
authors.forename: Liyan
authors.initials: L
authors.lastname: Chen
authors.forename: Baoshan
authors.initials: B
authors.lastname: Yang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Zhongping
authors.initials: Z
authors.lastname: Duan
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Liu
authors.forename: Mei
authors.initials: M
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism*; D002950:Citrate (si)-Synthase / Q000378:metabolism*; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism*; D022781:Hepatocytes / Q000166:cytology / Q000201:enzymology*; D017114:Liver Failure, Acute / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000648:ultrastructure*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003576:Electron Transport Complex IV; D002334:Carnitine O-Palmitoyltransferase; D002950:Citrate (si)-Synthase