AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats

  • Hesham M. Mahmoud Cairo University Kasr Alainy, Faculty of Medicine, Pharmacology, Cairo, Egypt
  • Mona Osman Cairo University Kasr Alainy, Faculty of Medicine, Pharmacology, Cairo, Egypt
  • Osama Elshabrawy National Research Centre, Pharmacology, Cairo, Egypt
  • Heba M. I. Abdallah National Research Centre, Pharmacology, Cairo, Egypt
  • Ahmed Khairallah Pharmacology Department, National Research Centre, Dokki, Cairo 11211, Egypt
Keywords: Cannabinoid receptor 2, AM1241, Hepatic progenitor cells, IL-10, p53, Bile duct ligation, Liver fibrosis, CD34

Abstract

BACKGROUND: The cannabinoid receptor 2 (CB2) plays a pleiotropic role in the innate immunity and is considered a crucial mediator of liver disease. Cannabinoid CB2 receptor activation has been reported to attenuate liver fibrosis in CCl4 exposed mice and also plays a potential role in liver regeneration in a mouse model of I/R and protection against alcohol-induced liver injury.

AIM: In this study, we investigated the impact of CB2 receptors on the antifibrotic and regenerative process associated with cholestatic liver injury.

METHODS: Twenty-six rats had bile duct ligation co-treated with silymarin and AM1241 for 3 consecutive weeks. Serum hepatotoxicity markers were determined, and histopathological evaluation was performed.

RESULTS: Following bile duct ligation (BDL) for 3 weeks, there was increased aminotransferase levels, marked inflammatory infiltration and hepatocyte apoptosis with induced oxidative stress, as reflected by increased lipid peroxidation. Conversely, following treatment with the CB2 agonist, AM-1241, BDL rats displayed a reduction in liver injury and attenuation of fibrosis as reflected by expression of hydroxyproline and α-smooth muscle actin. AM1241 treatment also significantly attenuated lipid peroxidation end-products, p53-dependent apoptosis and also attenuated inflammatory process by stimulating IL-10 production. Moreover, AM1241 treated rats were associated with significant expression of hepatic progenitor/oval cell markers.

CONCLUSION: In conclusion, this study points out that CB2 receptors reduce liver injury and promote liver regeneration via distinct mechanisms including IL-10 dependent inhibition of inflammation, reduction of p53-reliant apoptosis and through stimulation of oval/progenitor cells. These results suggest that CB2 agonists display potent hepatoregenrative properties, in addition to their antifibrogenic effects.

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Published
2019-03-29
How to Cite
1.
Mahmoud HM, Osman M, Elshabrawy O, Abdallah HMI, Khairallah A. AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats. Open Access Maced J Med Sci [Internet]. 2019Mar.29 [cited 2020Nov.27];7(6):925-36. Available from: https://www.id-press.eu/mjms/article/view/oamjms.2019.194
Section
A - Basic Science