AM-1241 CB2 Receptor Agonist Attenuates Inflammation, Apoptosis and Stimulate Progenitor Cells in Bile Duct Ligated Rats
| Autor: | Osama A. El-Shabrawy, Heba Abdallah, Mona Osman, Hesham M. Mahmoud, Ahmed Khairallah |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
Agonist
p53 medicine.drug_class AM1241 Liver fibrosis lcsh:Medicine 030209 endocrinology & metabolism Inflammation Pharmacology Hepatic progenitor cells 03 medical and health sciences Liver disease 0302 clinical medicine Basic Science medicine Cannabinoid receptor type 2 030212 general & internal medicine Progenitor cell Cannabinoid receptor 2 Liver injury business.industry Bile duct lcsh:R General Medicine Bile duct ligation medicine.disease Liver regeneration medicine.anatomical_structure IL-10 lipids (amino acids peptides and proteins) CD34 medicine.symptom business |
| Zdroj: | Open Access Macedonian Journal of Medical Sciences, Vol 7, Iss 6 (2019) Open Access Macedonian Journal of Medical Sciences; Vol 7 No 6 (2019): Mar 30 (OAMJMS); 925-936 Open Access Macedonian Journal of Medical Sciences |
| ISSN: | 1857-9655 |
| Popis: | 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: | OpenAIRE |
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