[Excessive copper induces hepatocyte apoptosis and affects Bax and Bcl-2 expression in rat liver].
OBJECTIVE
To establish a hepatolenticular degeneration rat model with excessive copper, and investigate the effects of excessive copper deposits in the liver on hepatocyte apoptosis and Bax and Bcl-2 expression.


METHODS
Rat model of hepatolenticular degeneration was established by administering forages containing 1g/kg of copper sulfate and drinking water containing 0.185% copper sulfate. Copper level in the liver and serum and alanine aminotransferase (ALT) level in serum were measured using an atomic absorption spectrophotometer. The terminal deoxynucleotidyl transferase-mediated deoxyuridine 5-triphosphate nick-end labeling (TUNEL) method was used to detect hepatocyte apoptosis. Bax and Bcl-2 expression was observed by RT-PCR and imunohistochemistry staining. Quantification of positive cells was performed by image analyzer.


RESULTS
With more prolonged excessive copper ingestion, copper level in the liver and serum as well as ALT level in serum rose, and more apoptosis cells appeared in the liver. Bax and Bcl-2 expression increased significantly compared with controls fed a normal diet and progressively increased with more prolonged excessive copper ingestion. The progressively increased extent of Bcl-2 expression was lower than that of Bax expression, so the ratio of Bcl-2/Bax decreased with increasing excessive copper ingestion time.


CONCLUSIONS
Excessive copper deposits in the liver can induce hepatocyte apoptosis through an up-regulation of Bax expression.
Li
Yu-Wen
YW
Department of Pediatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Wang
Xiao-Hua
XH
Nin
Qin
Q
Luo
Xiao-Ping
XP
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D003300:Copper / Q000633:toxicity*; D022781:Hepatocytes / Q000187:drug effects* / Q000473:pathology; D008099:Liver / Q000737:chemistry / Q000378:metabolism*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000235:genetics*
D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D003300:Copper; D000410:Alanine Transaminase