Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model
BACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has...
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| Language: | English |
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Fundação Oswaldo Cruz (FIOCRUZ)
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| Series: | Memorias do Instituto Oswaldo Cruz |
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| Online Access: | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100338&lng=en&tlng=en |
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| author | Yasmine Amr Issa Samar Nabil El Achy Rasha Fadly Mady |
| author_facet | Yasmine Amr Issa Samar Nabil El Achy Rasha Fadly Mady |
| author_sort | Yasmine Amr Issa |
| collection | DOAJ |
| description | BACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection. |
| first_indexed | 2024-03-12T08:50:50Z |
| format | Article |
| id | doaj.art-57485edccfbf4468b49a90a29c5b9e26 |
| institution | Directory Open Access Journal |
| issn | 1678-8060 |
| language | English |
| last_indexed | 2024-03-12T08:50:50Z |
| publisher | Fundação Oswaldo Cruz (FIOCRUZ) |
| record_format | Article |
| series | Memorias do Instituto Oswaldo Cruz |
| spelling | doaj.art-57485edccfbf4468b49a90a29c5b9e262023-09-02T16:21:34ZengFundação Oswaldo Cruz (FIOCRUZ)Memorias do Instituto Oswaldo Cruz1678-806011410.1590/0074-02760190062S0074-02762019000100338Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis modelYasmine Amr IssaSamar Nabil El AchyRasha Fadly MadyBACKGROUND Formation of schistosomal granulomata surrounding the ova can result in schistosomiasis-associated liver fibrosis (SSLF). The current standard of treatment is praziquantel (PZQ), which cannot effectively reverse SSLF. The role of the cannabinoid (CB) receptor family in liver fibrosis has recently been highlighted. OBJECTIVES This study aimed to assess the therapeutic effect of CB1 receptor antagonism in reversing SSLF in a murine model of Schistosoma mansoni infection. METHODS One hundred male Swiss albino mice were divided equally into five groups: healthy uninfected control (group I), infected control (group II), PZQ treated (group III), rimonabant (RIM) (SR141716, a CB1 receptor antagonist)-treated (group IV) and group V was treated with combined PZQ and RIM. Liver sections were obtained for histopathological examination, alpha-1 smooth muscle actin (α-SMA) immunostaining and assessment of CB1 receptor expression using real-time polymerase chain reaction (RT-PCR). FINDINGS The most effective reduction in fibrotic marker levels and granuloma load was achieved by combined treatment with PZQ+RIM (group V): CB1 receptor expression (H = 26.612, p < 0.001), number of α-SMA-positive cells (F = 57.086, p < 0.001), % hepatic portal fibrosis (F = 42.849, p < 0.001) and number of granulomata (F = 69.088, p < 0.001). MAIN CONCLUSIONS Combining PZQ with CB1 receptor antagonists yielded the best results in reversing SSLF. To our knowledge, this is the first study to test this regimen in S. mansoni infection.http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100338&lng=en&tlng=encannabinoid receptor-1(CB1)schistosoma-associated liver fibrosisrimonabant (SR141716)praziquantelalpha smooth muscle actin |
| spellingShingle | Yasmine Amr Issa Samar Nabil El Achy Rasha Fadly Mady Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model Memorias do Instituto Oswaldo Cruz cannabinoid receptor-1(CB1) schistosoma-associated liver fibrosis rimonabant (SR141716) praziquantel alpha smooth muscle actin |
| title | Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model |
| title_full | Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model |
| title_fullStr | Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model |
| title_full_unstemmed | Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model |
| title_short | Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model |
| title_sort | cannabinoid receptor 1 antagonism a new perspective on treating a murine schistosomal liver fibrosis model |
| topic | cannabinoid receptor-1(CB1) schistosoma-associated liver fibrosis rimonabant (SR141716) praziquantel alpha smooth muscle actin |
| url | http://www.scielo.br/scielo.php?script=sci_arttext&pid=S0074-02762019000100338&lng=en&tlng=en |
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