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 α-smooth muscle actin-positive matrix-producing cells and Smad 2/3 activity critical to the fibrogenic potential of transforming growth factor beta 1 (TGF-β1). 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.
Wen-Ying
WY
Chen
Chun-Jung
CJ
Chen
Jiunn-Wang
JW
Liao
Frank Chiahung
FC
Mao
D000199:Actins / Q000378:metabolism; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology*; D002779:Cholestasis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017608:Chromium Compounds / Q000494:pharmacology*; D002908:Chronic Disease; D019587:Dietary Supplements; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D000199:Actins; D000975:Antioxidants; D002712:Chlorides; D017608:Chromium Compounds; D051899:Smad2 Protein; C497784:Smad2 protein, rat; D051900:Smad3 Protein; C497787:Smad3 protein, rat; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C017133:chromous chloride