Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats

Froh, Matthias and Conzelmann, Lars and Walbrun, Peter and Netter, Susanne and Wiest, Reiner and Wheeler, Michael D. and Lehnert, Mark and Uesugi, Takehiko and Scholmerich, Jurgen and Thurman, Ronald G. (2007) Heme oxygenase-1 overexpression increases liver injury after bile duct ligation in rats. WORLD JOURNAL OF GASTROENTEROLOGY, 13 (25). pp. 3478-3486. ISSN 1007-9327, 2219-2840

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Abstract

AIM: To investigate the effects of heme oxygenase-1 (HO-1) against oxidant-induced injury caused by bile duct ligation (BDL). METHODS: Either cobalt protoporphyrin (CoPP), a HO-1 inducer, or saline were injected intraperitoneally in male SD-rats. Three days later, BDL or sham-operations were performed. Rats were sacrificed 3 wk after BDL and livers were harvested for histology. Fibrosis was evaluated by sirius red staining and image analysis. Alpha-smooth muscular actin, which indicates activation of stellate cells, was detected by immunohistochemical staining, and cytokine and collagen- I alpha (Col- I alpha) mRNA expression was detected using RNase protection assays. RESULTS: Serum alanine transaminase increased 8-fold above normal levels one day after BDL. Surprisingly, enzyme release was not reduced in rats receiving CoPP. Liver fibrosis was evaluated 3 wk after BDL and the sirius red-positive area was found to be increased to about 7.8%. However, in CoPP pretreated rats sirius red-positive areas were increased to about 11.7% after BDL. Collagen- I alpha and TGF-beta mRNA increased significantly by BDL. Again, this effect was increased by HO-1 overexpression. CONCLUSION: Hepatic fibrosis-due to BDL is not reduced by the HO-1 inducer CoPP. In contrast, HO-1 overexpression increases liver injury in rats under conditions of experimental chronic cholestasis. (c) 2007 WJG. All rights reserved.

Item Type: Article
Uncontrolled Keywords: STELLATE CELL ACTIVATION; TUMOR-NECROSIS-FACTOR; OXIDATIVE STRESS; LIPID-PEROXIDATION; NITRIC-OXIDE; ISCHEMIA/REPERFUSION INJURY; HEPATIC MITOCHONDRIA; SUPEROXIDE-DISMUTASE; BILIARY OBSTRUCTION; GENE-EXPRESSION; heme oxygenase-1; bile duct ligation; chronic cholestasis; liver fibrosis; serum alanine transaminase; transforming growth factor-beta; tumor necrosis factor-I alpha; type I collagen
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Innere Medizin I
Depositing User: Dr. Gernot Deinzer
Date Deposited: 09 Dec 2020 09:14
Last Modified: 09 Dec 2020 09:14
URI: https://pred.uni-regensburg.de/id/eprint/32506

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