title: Mitochondria-initiated apoptosis triggered by oxidative injury play a role in total parenteral nutrition-associated liver dysfunction in infant rabbit model.
abstract: OBJECTIVE
  The aim of the study was to investigate oxidative injury and apoptosis as the mechanisms underlying total parenteral nutrition (TPN)-associated liver dysfunction.
  
  
  METHODS
  Twenty New Zealand rabbits (2 weeks old) were divided into 2 groups as follows: 10 in the control group (maternal feed) and 10 in the TPN group. The rabbits in the TPN group received continuous PN infusion through a silastic catheter inserted in the right jugular vein.
  
  
  RESULTS
  After 10 days of treatment, the serum levels of total bilirubin and bile acid were significantly higher in the TPN group than in the control group (P < .01, respectively). The light microscopic findings in the TPN rabbits included inflammatory cell infiltration and hepatic steatosis. Electron microscopy showed change in the cytosolic vacuoles and rare microvilli in the microbile duct. Moreover, 10 days of treatment resulted in an inhibition of the superoxide dismutase (SOD) activity in hepatocytes, an increase of the malondialdehyde level, a significant increase in cytochrome c release from the mitochondria, a significant increase in caspase 3 activity, and increased apoptosis (P < .01, individually).
  
  
  CONCLUSIONS
  Oxidative damage may be one of the essential mechanisms of TPN-associated liver dysfunction. Moreover, mitochondria-initiated apoptosis triggered by oxidative damage may play an important role in this process.
authors.affiliation: Department of Pediatric Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hong
authors.forename: Xiang
authors.initials: X
authors.lastname: Wang
authors.forename: Jiang
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Cai
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis; D001647:Bile Acids and Salts / Q000097:blood; D001663:Bilirubin / Q000097:blood; D016009:Chi-Square Distribution; D022781:Hepatocytes / Q000378:metabolism; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D008111:Liver Function Tests; D008930:Mitochondria, Liver / Q000473:pathology*; D018384:Oxidative Stress; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D011817:Rabbits; D018709:Statistics, Nonparametric; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D013482:Superoxide Dismutase; D001663:Bilirubin