Cannabinoid receptor-1 antagonism: a new perspective on treating a murine schistosomal liver fibrosis model

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.

Intake, nutrient digestibility, rumen parameters, growth rate, carcase characteristics and cannabinoid residues of sheep fed pelleted rations containing hemp (Cannabis sativa L.) stubble

“… Purohit et al (2010) also noted an increase in fatty liver as a result of THC and CBD abuse in humans. Further research on the effects of feeding hemp stubble on liver weights and the potential of reversing any such effects ( Issa et al, 2019 ) by using a withholding period prior to slaughter is warranted.…”

Hepatic Antifibrotic Pharmacotherapy: Are We Approaching Success?

“…In particular, OCA (an FXR agonist) has demonstrated clinical benefit among patients with NASH in phase III clinical trial, 47 pioglitazone (a PPARg antagonist), 48 rimonabant (CB1 antagonist) and other drugs are also undergoing trials. 49 OCA, as described above, might be the most promising drug candidate that reduces fibrosis in patients with NAFLD. Although treatment of patients with NASH with OCA given orally at 25 mg daily for 72 weeks was found to be safe in a phase II (FLINT) trial; of note, 33 (23%) of 141 patients in phase II developed pruritus.…”

“…In particular, OCA (an FXR agonist) has demonstrated clinical benefit among patients with NASH in phase III clinical trial, 47 pioglitazone (a PPARγ antagonist), 48 rimonabant (CB1 antagonist) and other drugs are also undergoing trials. 49 …”

Cannabis sativa: A Source of Antiparasitic Compounds?

“…Silencing CB1 and Nox1 and Nox4 expression bi siRNAs abolished the expression of fibrotic markers, indicating the involvement of CB1, eCBs and oxidative stress in the onset of fibrotic changes at liver [38]. Consistent with these notions, the combined treatment with antifluke compound (Praziquantel) with Rimonabant (SR141716, a CB1 antagonist) inhibited the expression of fibrotic markers and liver fibrosis in infected mice [39].…”