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Updated: Jan 26, 2026
08:56
Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis
Published on: February 10, 2015
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AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated
Hesham M Mahmoud1, Mona Osman1, Osama Elshabrawy2
1Cairo University Kasr Alainy, Faculty of Medicine, Pharmacology, Cairo, Egypt.
Open Access Macedonian Journal of Medical Sciences
|April 13, 2019
Summary
Cannabinoid receptor 2 (CB2) agonists reduce liver injury and promote regeneration. CB2 activation attenuates liver fibrosis, inflammation, and apoptosis while stimulating hepatic progenitor cells, suggesting therapeutic potential.
Area of Science:
- Immunology
- Hepatology
- Pharmacology
Background:
- The cannabinoid receptor 2 (CB2) is integral to innate immunity and liver disease pathogenesis.
- CB2 receptor activation demonstrates antifibrotic effects and plays a role in liver regeneration and protection against alcohol-induced liver injury.
Purpose of the Study:
- To investigate the role of CB2 receptors in the antifibrotic and regenerative processes of cholestatic liver injury.
- To evaluate the therapeutic potential of CB2 agonists in liver disease models.
Main Methods:
- Bile duct ligation (BDL) was performed on rats, followed by co-treatment with silymarin and the CB2 agonist AM1241 for three weeks.
- Serum hepatotoxicity markers were analyzed, and histopathological evaluations were conducted.
Main Results:
- BDL induced liver injury, inflammation, apoptosis, and oxidative stress, evidenced by elevated aminotransferases and lipid peroxidation.
- AM1241 treatment significantly reduced liver injury, fibrosis (hydroxyproline, α-smooth muscle actin), apoptosis (p53-dependent), and inflammation (IL-10 production).
- AM1241 treatment promoted the expression of hepatic progenitor/oval cell markers.
Conclusions:
- CB2 receptors mitigate liver injury and enhance liver regeneration through IL-10-mediated anti-inflammation, reduced p53-dependent apoptosis, and stimulation of oval/progenitor cells.
- CB2 agonists exhibit significant hepatoregenerative and antifibrogenic properties, indicating their therapeutic promise for liver diseases.
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