Cannabidiol interacts with the FXR/Nrf2 pathway and changes the CB1/CB2 receptors ratio in gentamicin-induced kidney injury in rats.

Objectives: Gentamicin-induced nephrotoxicity was used as an experimental model of kidney disease. The present study was performed to assess the therapeutic role of cannabidiol (CBD) against gentamicin-induced renal damage.

Materials And Methods: Forty two male Wistar rats were randomly allocated into 6 groups (n=7), including: (1) Control, (2) Vehicle, (3) Gentamicin-treated group (100 mg/kg/day) for 10 days (GM), (4-6) 3 Gentamicin-CBD-treated groups (2.5, 5, and 10 mg/kg/day) for 10 days (GM+CBD2.5, GM+CBD5, GM+CBD10). Serum levels of BUN and Cr, renal histology as well as real-time qRT-PCR were used to investigate the pattern of changes at different levels.

Results: Gentamicin increased serum BUN and Cr (<0.001), down-regulation of FXR (<0.001), SOD (<0.05) and up-regulation of CB1 receptor mRNA (<0.01). Compared to the control group, CBD at 5 decreased (<0.05) and at 10 mg/kg/day increased the expression of FXR (<0.05). Nrf2 expression in CBD groups was increased (<0.001 vs. GM). The expression of TNF-α compared to the control and GM groups, was significantly increased in CBD2.5 (<0.01) and CBD10 (<0.05). Compared to the control, CBD at 2.5 (<0.01), 5 (<0.001) and 10 (<0.001) mg/kg/day significantly increased the expression of CB1R. Up-regulation of CB1R in the GM+CBD5, was significantly higher (<0.05) than the GM group. Compared to the control group, the most significant increase in CB2 receptor expression was observed at CBD10 (<0.05).

Conclusion: CBD particularly at 10 mg/kg/day might be of significant therapeutic benefit against such renal complications. Activating the FXR/Nrf2 pathway and counteracting the deleterious effects of CB1 receptors via CB2 receptors scale-up could be part of the protective mechanisms of CBD.