Antioxidant effect of cannabidiol in mice with liver fibrosis

  Objective  To explore antioxidant effect of cannabidiol (CBD) in mice with carbon tetrachloride (CCl4)-induced liver fibrosis.

  Methods  Forty male C57BL/6J mice were divided into five groups: a control and a model group, two CBD groups (4 mg/kg and 8 mg/kg) and a colchicine (0.2 mg/kg) group. Intraperitoneal administration of carbon tetrachloride (CCl4) at the dosage of 5 mL/kg body weight was performed for all the mice twice a week for consecutive ten weeks except for those of the control group with intraperitoneal injection of peanut oil; meanwhile, the mice of CBD and colchicine groups were intraperitoneally injected with corresponding dose of medication each time and the control mice with saline. Serum alanine aminotransferase (ALT) was measured with an automatic biochemical analytic instrument; collagen deposition of liver tissue was examined with sirius red staining; superoxide dismutase (SOD), reduced glutathione (GSH) and malondialdehyde (MDA) were measured using commercial kits; gp91/Nrf2 in liver specimens was assessed with Western blot.

  Results  In the mice of treated with low/high CBD and colchicine, significantly lower liver index (4.71 ± 0.34%/4.68 ± 0.20% and 4.24 ± 0.40%), serum ALT (79.38 ± 14.79/87.13 ± 9.40 and 77.88 ± 3.76 U/L), MDA in liver tissues (2.48 ± 0.43/2.74 ± 0.88 and 2.84 ± 0.87 nmol/mgprot) and significantly increased SOD (259.90 ± 36.05/223.13 ± 37.49 and 246.39 ± 53.49 U/mgprot) and GSH (63.07 ± 16.71/100.38 ± 22.44 and 96.39 ± 19.40 nmol/mgprot) in liver tissues were detected compared with those in the model rats (P < 0.05 for all); obviously ameliorated collagen deposition, down-regulated protein expression of gp91 but up-regulated and protein expression of nuclear factor-erythroid 2-related factor-2 (Ntf2) were also observed in liver tissues of the low/high CBD and colchicine groups (all P < 0.05).

  Conclusion  The results suggeste that CBD has protective effect on CCl4-induced liver fibrosis in mice, probably via adjusting protein expression of gp91 and Nrf2, clearing free radicals and inhibiting the occurrence of lipid peroxidation.