Protective effects of rutin on liver injury induced by biliary obstruction in rats.

Abstract

Rutin has been shown to possess beneficial health effects, including hepatoprotection. However, to date, it has not been demonstrated to have a hepatoprotective effect against cholestatic liver injury. This is the first report to show a protective effect of rutin on cholestatic liver injury. Cholestasis was produced by bile duct ligation (BDL) in male Sprague-Dawley rats for 3 weeks. Daily oral administration of rutin was started 1 week before injury and was maintained for 4 weeks. In comparison with the control group, the BDL group showed liver injury as evidenced by histological changes and elevation in serum biochemicals, ductular reaction, fibrosis, inflammation, and oxidative stress. These pathophysiological changes were attenuated by rutin supplementation. Rutin alleviated BDL-induced transforming growth factor β1 (TGF-β1), interleukin-1β, connective tissue growth factor, and collagen expression. The antifibrotic effect of rutin was accompanied by reductions in α-smooth muscle actin-positive matrix-producing cells and Smad2/3 activity critical to the fibrogenic potential of TGF-β1. Rutin attenuated BDL-induced oxidative stress, leukocyte accumulation, NF-κB activation, and proinflammatory cytokine production. Further studies demonstrated an inhibitory effect of rutin on the redox-sensitive intracellular signaling molecule extracellular signal-regulated kinase (ERK). Rutin also attenuated BDL-induced reduction in NF-E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and AMP-activated protein kinase (AMPK). Taken together, the beneficial effects of rutin were shown to be associated with antioxidative and anti-inflammatory effects as well as the downregulation of NF-κB and TGF-β/Smad signaling, probably via interference of ERK activation and/or enhancement of Nrf2, HO-1, and AMPK activity.

• Authors: Pin-Ho Pan, Shih-Yi Lin, Ya-Yu Wang, Wen-Ying Chen, Yu-Han Chuang, Chih-Cheng Wu, Chun-Jung Chen
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 73 Pg. 106-16 (Aug 2014) ISSN: 1873-4596 [Electronic] United States
• PMID: 24815012 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2014 Elsevier Inc. All rights reserved.

Chemical References

• Actins
• Anti-Inflammatory Agents
• Antioxidants
• Interleukin-1beta
• NF-E2-Related Factor 2
• NF-kappa B
• Nfe2l2 protein, rat
• Smad2 Protein
• Smad2 protein, rat
• Smad3 Protein
• Smad3 protein, rat
• Transforming Growth Factor beta1
• smooth muscle actin, rat
• Connective Tissue Growth Factor
• Rutin
• Collagen
• Peroxidase
• Heme Oxygenase-1
• Extracellular Signal-Regulated MAP Kinases
• AMP-Activated Protein Kinases
• Glutathione

Topics

• AMP-Activated Protein Kinases (metabolism)
• Actins (biosynthesis)
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Antioxidants (therapeutic use)
• Biliary Tract (pathology)
• Biliary Tract Surgical Procedures
• Cholestasis (drug therapy)
• Collagen (biosynthesis)
• Connective Tissue Growth Factor (biosynthesis)
• Extracellular Signal-Regulated MAP Kinases (antagonists & inhibitors)
• Glutathione (analysis)
• Heme Oxygenase-1 (metabolism)
• Inflammation (drug therapy)
• Interleukin-1beta (biosynthesis)
• Liver (drug effects, injuries)
• Liver Cirrhosis (drug therapy)
• Male
• NF-E2-Related Factor 2 (metabolism)
• NF-kappa B (metabolism)
• Oxidative Stress (drug effects)
• Peroxidase (metabolism)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Rutin (therapeutic use)
• Smad2 Protein (metabolism)
• Smad3 Protein (metabolism)
• Transforming Growth Factor beta1 (biosynthesis)