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Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model

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Author(s)
Jung-Yeon KimYongmin ChoiJaechan LeemJeong Eun Song
Keimyung Author(s)
Choi, Yong Min
Department
Dept. of Rehabilitation Medicine (재활의학)
Journal Title
Int J Mol Sci
Issued Date
2021
Volume
22
Issue
15
Keyword
heme oxygenase-1cholestatic liver diseaseoxidative stressapoptosisinflammationfibrosis
Abstract
Cholestatic liver diseases can progress to end-stage liver disease and reduce patients' quality of life. Although their underlying mechanisms are still incompletely elucidated, oxidative stress is considered to be a key contributor to these diseases. Heme oxygenase-1 (HO-1) is a cytoprotective enzyme that displays antioxidant action. It has been found that this enzyme plays a protective role against various inflammatory diseases. However, the role of HO-1 in cholestatic liver diseases has not yet been investigated. Here, we examined whether pharmacological induction of HO-1 by cobalt protoporphyrin (CoPP) ameliorates cholestatic liver injury. To this end, a murine model of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet feeding was used. Administration of CoPP ameliorated liver damage and cholestasis with HO-1 upregulation in DDC diet-fed mice. Induction of HO-1 by CoPP suppressed the DDC diet-induced oxidative stress and hepatocyte apoptosis. In addition, CoPP attenuated cytokine production and inflammatory cell infiltration. Furthermore, deposition of the extracellular matrix and expression of fibrosis-related genes after DDC feeding were also decreased by CoPP. HO-1 induction decreased the number of myofibroblasts and inhibited the transforming growth factor-β pathway. Altogether, these data suggest that the pharmacological induction of HO-1 ameliorates cholestatic liver disease by suppressing oxidative stress, hepatocyte apoptosis, and inflammation.
Keimyung Author(s)(Kor)
최용민
Publisher
School of Medicine (의과대학)
Citation
Jung-Yeon Kim et al. (2021). Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model. Int J Mol Sci, 22(15), 8253. doi: 10.3390/ijms22158253
Type
Article
ISSN
1422-0067
Source
https://www.mdpi.com/1422-0067/22/15/8253
DOI
10.3390/ijms22158253
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43954
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Rehabilitation Medicine (재활의학)
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