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

Autor:	Mahmoud HM; Cairo University Kasr Alainy, Faculty of Medicine, Pharmacology, Cairo, Egypt., Osman M; Cairo University Kasr Alainy, Faculty of Medicine, Pharmacology, Cairo, Egypt., Elshabrawy O; National Research Centre, Pharmacology, Cairo, Egypt., Abdallah HMI; National Research Centre, Pharmacology, Cairo, Egypt., Khairallah A; Pharmacology Department, National Research Centre, Dokki, Cairo 11211, Egypt.
Jazyk:	angličtina
Zdroj:	Open access Macedonian journal of medical sciences [Open Access Maced J Med Sci] 2019 Mar 29; Vol. 7 (6), pp. 925-936. Date of Electronic Publication: 2019 Mar 29 (Print Publication: 2019).
DOI:	10.3889/oamjms.2019.194
Abstrakt:	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.
Databáze:	MEDLINE
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