Cannabidiol attenuates cisplatin‐induced nephrotoxicity by decreasing oxidative/nitrosative stress, inflammation and cell death

Abstract

The platinum compound cisplatin is one of the most potent chemotherapy agents available to treat various malignancies. Nephrotoxicity is a common complication of cisplatin chemotherapy, which involves increased oxidative and nitrosative stress, limiting its clinical use. In this study we have investigated the effects of a nonpsychoactive cannabinoid cannabidiol, which was reported to exert antioxidant effects and has recently been approved for the treatment of inflammation, pain, and spasticity associated with multiple sclerosis in patients, in a mouse model of cisplatin‐induced nephropathy. Cisplatin induced increased expression of superoxide generating enzymes RENOX and NOX1,, enhanced ROS generation, nitrotyrosine formation, apoptosis , PARP activity, and inflammation in the kidneys of mice, associated with marked histopathological damage and impaired renal function. Pretreatment of mice with cannabidiol markedly attenuated the cisplatin‐induced oxidative/nitrosative stress, inflammation and cell death in the kidney, and improved renal function. Thus, our results suggest that cannabidiol may represent a promising new protective strategy against cisplatin‐induced nephrotoxicity.