Heme Oxygenase-1 Induction by Cobalt Protoporphyrin Ameliorates Cholestatic Liver Disease in a Xenobiotic-Induced Murine Model.
Jung-Yeon KimYongmin ChoiJaechan LeemJeong Eun SongPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- liver injury
- oxidative stress
- drug induced
- diabetic rats
- pi k akt
- transforming growth factor
- extracellular matrix
- dna damage
- ischemia reperfusion injury
- induced apoptosis
- weight loss
- poor prognosis
- mouse model
- liver fibrosis
- physical activity
- end stage renal disease
- signaling pathway
- stem cells
- epithelial mesenchymal transition
- cell therapy
- newly diagnosed
- metabolic syndrome
- hydrogen peroxide
- heat shock
- cell death
- skeletal muscle
- cell proliferation
- single cell
- ejection fraction
- type diabetes
- endoplasmic reticulum stress
- carbon nanotubes
- atomic force microscopy
- prognostic factors
- machine learning
- artificial intelligence
- big data
- reduced graphene oxide
- electronic health record
- high glucose
- insulin resistance