Oxidative injury and hepatocyte apoptosis in total parenteral nutrition-associated liver dysfunction.
OBJECTIVE
The aim of this study was to investigate the impact of oxidative injury and apoptosis on total parenteral nutrition (TPN)-associated hepatic dysfunction.


METHODS
Fifty-nine New Zealand rabbits (6-8 days old) were divided into 4 groups: 12 in the control group (maternal fed), 15 in the PN-3 group (TPN for 3 days), 14 in the PN-7 group (TPN for 7 days), and 18 in the PN-10 group (TPN for 10 days). At the end of the experiment, blood biochemistry analysis and histologic examination of the liver were performed; the malondialdehyde content of liver tissues was determined and hepatocyte apoptosis was evaluated by terminal deoxynucleotidyl transferase-mediated nick-end labeling assay.


RESULTS
We found that the serum level of direct bilirubin became higher as PN duration was extended. The light microscopy features in the PN-3 and PN-7 groups included inflammatory cells infiltrated in portal areas and some degeneration changes, whereas in the PN-10 group, cholestasis (proliferation of bile ducts and bile pigments in hepatocytes) or diffuse steatosis was shown. Electron microscopic manifestation in PN groups included reduced numbers of microvilli and some preapoptosis changes. Both the malondialdehyde content and apoptosis index were the highest in the PN-10 group; there were more apoptotic hepatocytes in the groups with longer PN duration.


CONCLUSIONS
The longer the TPN duration, the more severe the liver injury. Both oxidative injury and apoptosis may play important roles in the mechanism of TPN-associated hepatic dysfunction.
Cai
Wei
W
Clinical Nutrition Center, Department of Pediatric Surgery, Xin Hua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiaotong University, Shanghai 200092, China. caiw204@yahoo.com.cn
Wu
Jiang
J
Hong
Li
L
Xu
Yuanfei
Y
Tang
Qingya
Q
Shi
Chengren
C
D000818:Animals; D017209:Apoptosis; D001663:Bilirubin / Q000097:blood; D022781:Hepatocytes; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D008107:Liver Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D008111:Liver Function Tests; D008315:Malondialdehyde / Q000378:metabolism; D018384:Oxidative Stress; D010289:Parenteral Nutrition, Total / Q000009:adverse effects*; D011817:Rabbits; D012720:Severity of Illness Index; D013997:Time Factors
D008315:Malondialdehyde; D001663:Bilirubin