Journal
LIFE SCIENCES
Volume 84, Issue 17-18, Pages 606-614Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2009.02.003
Keywords
Cholestasis; Chromium; Hepatotoxicity; Oxidative stress
Funding
- National Science Council [NSC95-2622-B-005-001]
- Taichung Veterans General Hospital
- National Chung Hsing University [TCVGH-NCHU-957602]
- Ministry of Education (Taiwan)
- Maxluck Biotechnology Corporation, Taipei, Taiwan
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Aims: 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. Main 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. Key findings: 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-beta 1). In addition, chromium effectively attenuated BDL-induced hepatic oxidative stress. Significance: The data indicate that chromium attenuates BIDL-induced cholestatic liver injury, bile duct proliferation, and fibrosis. The hepatoprotective effect of chromium is associated with antioxidative potential. (C) 2009 Elsevier Inc. All rights reserved.
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