Mitochondria-initiated apoptosis triggered by oxidative injury play a role in total parenteral nutrition-associated liver dysfunction in infant rabbit model.
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.
Hong
Li
L
Department of Pediatric Surgery, Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
Wang
Xiang
X
Wu
Jiang
J
Cai
Wei
W
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
D001647:Bile Acids and Salts; D013482:Superoxide Dismutase; D001663:Bilirubin