title: Hepatoprotective effects and mechanisms of dehydrocavidine in rats with carbon tetrachloride-induced hepatic fibrosis.
abstract: OBJECTIVE
  The current study was designed to examine the effects and possible mechanisms of dehydrocavidine (DC) on carbon tetrachloride (CCl4)-induced hepatic fibrosis in male Sprague-Dawley (SD) rats.
  
  
  METHODS
  Hepatic fibrosis was induced in male rats with CCl4 administration for 12 weeks. Liver histopathological study was performed, and the liver function was examined by determining the serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH) and total bilirubin (TBIL) for evaluating the effect of DC on hepatic fibrosis. The possible mechanisms were investigated by measuring hepatic collagen metabolism and oxidative stress level. Furthermore, oligo microarray analysis of 263 genes was performed, and quantitative real-time RT-PCR was used to verify 4 of the abnormally expressed genes (Bcl2, Cyp3a13, IL18 and Rad50).
  
  
  RESULTS
  DC treatment significantly inhibited the loss of body weight and the increase of liver weight induced by CCl4. DC also improved the liver function of rats as indicated by decreased serum enzymatic activities of ALT, AST, ALP and TBIL. Histopathological results indicated that DC alleviated liver damage and reduced the formation of fibrous septa. Moreover, DC significantly decreased liver hydroxyproline (Hyp) and increased urine Hyp. It also decreased liver malondialdehyde concentration, increased activities of liver superoxide dismutase, catalase and glutathione peroxidase. Microarray analysis revealed that DC altered the expression of genes related to apoptosis, cytokines and other proteins involved in tissue repair.
  
  
  CONCLUSIONS
  Our findings indicate that DC can protect rats from CCl4-induced hepatic fibrosis through reducing oxidative stress, promoting collagenolysis, and regulating fibrosis-related genes.
authors: Center for New Drug Evaluation, Institute of Basic Medical Science, Second Military Medical University, No. 800 Xiang Yin Road, Shanghai 200433, China.
authors: Tao
authors: T
authors: Wang
authors: Li-Jun
authors: LJ
authors: Zhao
authors: Ping
authors: P
authors: Li
authors: Hua
authors: H
authors: Jiang
authors: Guo-Cai
authors: GC
authors: Lu
authors: Wei-Dong
authors: WD
authors: Zhang
authors: Hui-Liang
authors: HL
authors: Li
authors: Bo-Jun
authors: BJ
authors: Yuan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001600:Berberine Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D002251:Carbon Tetrachloride; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D031311:Corydalis / Q000737:chemistry*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006909:Hydroxyproline / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000209:etiology; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D046228:Microarray Analysis; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015431:Weight Loss / Q000187:drug effects
chemical_list: D000975:Antioxidants; D001600:Berberine Alkaloids; D016207:Cytokines; D010936:Plant Extracts; C011188:cavidine; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D006909:Hydroxyproline