Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model
Mem. Inst. Oswaldo Cruz
; 114: e190062, 2019. tab, graf
Article
в En
| LILACS
| ID: biblio-1012673
Ответственная библиотека:
BR1.1
ABSTRACT
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.
Key words
Полный текст:
1
База данных:
LILACS
Основная тема:
Fibrosis
/
Typhus, Endemic Flea-Borne
/
Liver
Тип исследования:
Prognostic_studies
Пределы темы:
Humans
Язык:
En
Журнал:
Mem. Inst. Oswaldo Cruz
Тематика журнала:
MEDICINA TROPICAL
/
PARASITOLOGIA
Год:
2019
Тип:
Article