Cannabidiol attenuates arsenic-induced nephrotoxicity via the NOX4 and NF-κB pathways in mice
Ali Vadizadeh1,2, Maryam Salehcheh1,3, Hadi Kalantar3
1Department of Toxicology, Faculty of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Background And Purpose:
Cannabidiol (CBD) is a phenolic terpene compound with anticancer, antioxidant, anti-inflammatory, antibacterial, neuroprotective, and anticonvulsant properties. Since the effects of CBD on sodium arsenite (As)-induced nephrotoxicity have not been fully determined, this study investigated the effect of CBD on As-induced nephrotoxicity by evaluating the NOX4 and NF-kB pathways in mice.
Experimental Approach:
48 male mice were divided into six groups (8 each) including group 1, receiving saline for 14 days; group 2, receiving CBD (10 mg/kg, intraperitoneally) from the 7th to the 14th day; group 3, receiving As (10 mg/kg) for 14 days by gavage; and treatment groups 4-6, receiving CBD (2.5, 5, and 10 mg/kg, i.p.) 1.5 h before As (10 mg/kg by gavage, for 14 days) from the 7th to the 14th day. Mice were anesthetized after overnight fasting on day 15, and the blood sample was collected from their hearts. The level of antioxidants and pro-inflammatory factors, the expression of ROS and TNF-α, NF-kB, NOX4, iNOS, cleaved PARP, and caspase-3 proteins were measured and histological studies were performed.
Findings/Results:
Exposure to As significantly increased kidney markers, oxidative stress, apoptosis, and inflammation in mice kidney tissue, and pretreatment with CBD reversed these changes. In addition, CBD significantly decreased the expression of NF-kB and NOX4, and the levels of pro-inflammatory factors and the expression of cleaved PARP and increased the level of antioxidants.
Conclusion And Implications:
CBD ameliorated As-induced nephrotoxicity related to inhibiting oxidative stress, inflammation, and apoptosis, potentially through the NF-kB/Nox4 pathway.
Insights
Cannabidiol (CBD) protects against arsenic-induced kidney damage by reducing oxidative stress and inflammation. This study shows CBD inhibits the NF-kB/Nox4 pathway, offering a potential therapeutic strategy for nephrotoxicity.
Area of Science:
- Toxicology
- Pharmacology
- Biochemistry
Background:
- Cannabidiol (CBD) possesses diverse therapeutic properties, including antioxidant and anti-inflammatory effects.
- The impact of CBD on sodium arsenite (As)-induced nephrotoxicity remains incompletely understood.
- Investigating CBD's protective mechanisms against As-induced kidney damage is crucial.
Purpose of the Study:
- To determine the protective effects of Cannabidiol (CBD) against sodium arsenite (As)-induced nephrotoxicity in mice.
- To elucidate the role of the NOX4 and NF-kB pathways in CBD's amelioration of As-induced kidney injury.
- To evaluate the impact of CBD on oxidative stress, inflammation, and apoptosis markers in the kidney.
Main Methods:
- A mouse model was used, with groups receiving saline, CBD, As, or CBD pretreatment before As exposure.
- Biochemical assays measured antioxidant and pro-inflammatory factors, oxidative stress markers (ROS), and apoptosis markers (cleaved PARP, caspase-3).
- Protein expression of NF-kB, NOX4, and iNOS was assessed, alongside histological examination of kidney tissues.
Main Results:
- Arsenite exposure significantly elevated kidney damage markers, oxidative stress, apoptosis, and inflammation.
- CBD pretreatment dose-dependently reversed these As-induced detrimental effects.
- CBD significantly reduced NF-kB and NOX4 expression, pro-inflammatory cytokines, and apoptosis, while increasing antioxidant levels.
Conclusions:
- Cannabidiol (CBD) effectively ameliorates As-induced nephrotoxicity in mice.
- CBD's protective effects are associated with the inhibition of oxidative stress, inflammation, and apoptosis.
- The NF-kB/Nox4 signaling pathway is implicated in CBD's renoprotective mechanism against arsenic toxicity.
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