Cannabidiol interacts with the FXR/Nrf2 pathway and changes the CB1/CB2 receptors ratio in gentamicin-induced kidney injury in rats | ||
| Iranian Journal of Basic Medical Sciences | ||
| مقاله 11، دوره 26، شماره 3، خرداد 2023، صفحه 343-350 اصل مقاله (1.25 M) | ||
| نوع مقاله: Original Article | ||
| شناسه دیجیتال (DOI): 10.22038/ijbms.2023.67998.14867 | ||
| نویسندگان | ||
| Vahideh Hokmabady1؛ Azadeh Khalili2؛ Seyed Ali Hashemi3؛ Keshvad Hedayatyanfard2؛ Soraya Parvari4؛ Saeed Changizi-Ashtiyani* 1؛ Gholamreza Bayat* 2 | ||
| 1Department of Physiology, School of Medicine, Arak University of Medical Sciences, Arak, Iran | ||
| 2Department of Physiology, Pharmacology, Medical Physics, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran | ||
| 3Department of Pathology, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran | ||
| 4Department of Anatomical Sciences, School of Medicine, Alborz University of Medical Sciences, Karaj, Iran | ||
| چکیده | ||
| Objective(s): 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 (P<0.001), down-regulation of FXR (P<0.001), SOD (P<0.05) and up-regulation of CB1 receptor mRNA (P<0.01). Compared to the control group, CBD at 5 decreased (P<0.05) and at 10 mg/kg/day increased the expression of FXR (P<0.05). Nrf2 expression in CBD groups was increased (P<0.001 vs. GM). The expression of TNF-α compared to the control and GM groups, was significantly increased in CBD2.5 (P<0.01) and CBD10 (P<0.05). Compared to the control, CBD at 2.5 (P<0.01), 5 (P<0.001) and 10 (P<0.001) mg/kg/day significantly increased the expression of CB1R. Up-regulation of CB1R in the GM+CBD5, was significantly higher (P<0.05) than the GM group. Compared to the control group, the most significant increase in CB2 receptor expression was observed at CBD10 (P<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. | ||
| کلیدواژهها | ||
| Cannabidiol؛ CB1 Receptors؛ CB2 Receptors؛ Farnesoid receptors؛ Gentamicin؛ Nrf2 | ||
| مراجع | ||
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