title: [Effects of 4-phenylbutyric acid on carbon tetrachloride-induced acute liver injury in mice].
abstract: OBJECTIVE
  To explore the effects and the molecular mechanisms of 4-phenylbutyric acid (PBA) on carbon tetraehloride (CCl4)-induced acute liver injury in mice.
  
  
  METHODS
  Sixty adult, healthy, male ICR mice were divided equally into the control group, PBA group, CCl4 12 h group, CCl4 24 h group, CCl4 48 h group, CCl4 72 h group, PBA+CCl4 12 h group, PBA+CCl4 24 h group, PBA+CCl4 48 h group, and PBA+CCl4 72 h group. The CCl4 groups and the PBA+CCl4 groups were intraperitoneally (i.p.) injected with CCl4 (300 mL/kg). In the PBA+CCl4 groups, the mice were i.p. injected with PBA (400 mg/kg). All mice were sacrificed to collect blood and liver specimens at different time points after the CCl4 treatment. Serum alanine aminotransferase (ALT) was detected. Histological examination was performed using hematoxylin-eosin staining and light microscopy, and apoptosis was detected using terminal transferase dUTP nick end labeling. The hepatic distribution of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The hepatic protein expression of glucose-regulated protein (GRP78), C/EBP homologousprotein (CHOP), phosphorylated c-Jun N-terminal kinases (p-JNK), phosphorylated eukaryotic initiation factor 2a subunit (p-eIF2a), phosphorylated serine threonine kinase (p-akt), and nuclear factor-kappa B p65 (NF-kappa Bp65) were determined by western blot.
  
  
  RESULTS
  The serum ALT level in the PBA+CCl4 groups was reduced as compared with that in the CCl4 groups at the various time points examined.The liver-to-body weight ratio of two groups showed a significant difference only at the 48 h time point (P<0.01). PBA reduced the degree of hepatic necrosis and apoptosis caused by CCl4, and reduced the expression of hepatic GRP78 and other endoplasmic reticulum stress-related proteins (P<0.01). The protein levels of p-akt, NF-kappa Bp65 and PCNA was significantly decreased in the PBA+CCl4 groups (P<0.01).
  
  
  CONCLUSIONS
  The endoplasmic reticulum stress inhibitor PBA alleviated acute hepatic necrosis and apoptosis but restrained hepatic proliferation.
authors.affiliation: Department of Gastroenterology, the First Affiliated Hospital, Anhui Medical University, Hefei 230022, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qi
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Cheng
authors.initials: C
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Tao
authors.forename: Wei
authors.initials: W
authors.lastname: He
authors.forename: Jianqing
authors.initials: J
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Dexiang
authors.initials: D
authors.lastname: Xu
mesh_terms: D000410:Alanine Transaminase; D000818:Animals; D017209:Apoptosis; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress; D018840:HSP70 Heat-Shock Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B; D010654:Phenylbutyrates; D010766:Phosphorylation
chemical_list: D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; C000717248:Hspa5 protein, mouse; D008565:Membrane Proteins; D016328:NF-kappa B; D010654:Phenylbutyrates; C018551:glucose-regulated proteins; C075773:4-phenylbutyric acid; D002251:Carbon Tetrachloride; D000410:Alanine Transaminase