Chromium attenuates hepatic damage in a rat model of chronic cholestasis.
OBJECTIVE
Oxidative stress is involved in cholestasis-induced hepatic damage. Therefore, antioxidant therapy is a recommended therapeutic strategy. Studies have illustrated that chromium can enhance antioxidative capacity leading to a resolution of oxidative stress. The aim of this study was to assess whether chromium has protective effects against cholestasis-related liver damage.


METHODS
Cholestasis was produced by bile duct ligation (BDL) in male Sprague-Dawley rats for 3 weeks. Rats were randomly divided into four groups. Control and BDL groups were subjected to sham and BDL operation, respectively, and were supplemented with placebo for 3 weeks. The BDL-post Cr group was supplemented with chromium chloride for 3 weeks after BDL operation. The BDL-pre Cr group was supplemented with chromium chloride for 6 weeks starting from 3 weeks before BDL operation.


RESULTS
In comparison with the control group, the BDL group showed hepatic damage as evidenced by elevation in serum biochemicals, ductular reaction, and fibrosis. These pathophysiological changes were attenuated in the BDL-Pre Cr and BDL-Post Cr groups. However, there was no significant difference between these two groups. The anti-fibrotic effect of chromium was accompanied by reductions in alpha-smooth muscle actin-positive matrix-producing cells and Smad 2/3 activity critical to the fibrogenic potential of transforming growth factor beta 1 (TGF-beta1). In addition, chromium effectively attenuated BDL-induced hepatic oxidative stress.


CONCLUSIONS
The data indicate that chromium attenuates BDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of chromium is associated with antioxidative potential.
Chen
Wen-Ying
WY
Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan.
Chen
Chun-Jung
CJ
Liao
Jiunn-Wang
JW
Mao
Frank Chiahung
FC
D000818:Animals; D015153:Blotting, Western; D002779:Cholestasis / Q000473:pathology*; D002857:Chromium / Q000633:toxicity*; D002908:Chronic Disease; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D002857:Chromium