title: Dangfei liganning capsules attenuate the susceptibility of rat nonalcoholic fatty liver to carbon tetrachloride toxicity.
abstract: OBJECTIVE
  To test whether nonalcoholic hepatic steatosis sensitizes carbon tetrachloride (CCl4)-induced liver injury, and to assess the therapeutic effect of Chinese medicine extracts of Dangfei Liganning capsules and their potential underlying mechanisms.
  
  
  METHODS
  Male Wistar rats were fed a high-fat diet to induce nonalcoholic fatty liver disease (NAFLD) or a normal diet (N). Eight weeks later, a nonlethal dose of CCl4 was applied intraperitoneally. From the start, HF-CCl4 rats were administered daily Dangyao extracts (D), Dangfei Liganning capsules (DF), or Diammonium Glycyrrhizinate (G) intragastrically. Rats were sacrificed 48 h after CCl4 administration. In addition to serum biochemistry, liver histopathology was observed using hematoxylin-eosin (HE) and oil red O staining, and hepatic levels of triglyceride (TG), malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), caspase-3 activation and cytochrome P450 (CYP2E1) expression were assessed.
  
  
  RESULTS
  There was almost no response to the nonlethal dose of CCl4 in the N control group. However, the HF group demonstrated massive steatosis, and elevated levels of serum ALT and AST, liver MDA, CYP2E1, and caspase-3 activation, whereas the levels of GSH and SOD were significantly decreased. All indexes assessed were dramatically worse in the HF-CCl4 group compared to the HF group, in addition to the more severe steatosis, hepatocyte ballooning, and inflammatory infiltration apparent in the centrilobular area. The medicines we tested affected the pathological changes in HF-CCl4 rats to differing degrees: DF and G led to improvements in all of the above examined indexes, including an obvious improvement in histopathology, and DF improved serum ALT and MDA levels more markedly than G, whereas D extracts produced only mild liver injury attenuation.
  
  
  CONCLUSIONS
  Liver with NAFLD is more sensitive to hepatotoxicity; furthermore, the disrupted balance of oxidative stress and anti-oxidant defense contributes to the underlying mechanisms. Dangfei Liganning capsules potentially decrease this toxic susceptibility and alleviate liver injury in non-alcoholic fatty liver.
authors.affiliation: Institute of Digestive Disease, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Song
authors.forename: Zhi-Min
authors.initials: ZM
authors.lastname: Mao
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.forename: Dong-Fei
authors.initials: DF
authors.lastname: Li
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.forename: Ying-Li
authors.initials: YL
authors.lastname: Ge
authors.forename: Pei-Yong
authors.initials: PY
authors.lastname: Zheng
authors.forename: Ping
authors.initials: P
authors.lastname: Liu
authors.forename: Xiao-Qi
authors.initials: XQ
authors.lastname: Zhang
authors.forename: Guang
authors.initials: G
authors.lastname: Ji
mesh_terms: D000818:Animals; D002214:Capsules / Q000008:administration & dosage; D002251:Carbon Tetrachloride / Q000633:toxicity*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000008:administration & dosage*; D005234:Fatty Liver / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D065626:Non-alcoholic Fatty Liver Disease; D051381:Rats; D017208:Rats, Wistar
chemical_list: D002214:Capsules; D004365:Drugs, Chinese Herbal; D008315:Malondialdehyde; D002251:Carbon Tetrachloride; D019392:Cytochrome P-450 CYP2E1; D053148:Caspase 3; D005978:Glutathione