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 (NOX4) and NOX1, enhanced reactive oxygen
species generation, inducible nitric-oxide synthase expression,
nitrotyrosine formation, apoptosis (caspase-3/7 activity, DNA
fragmentation, and terminal deoxynucleotidyl transferase dUTP
nick-end labeling staining), poly(ADP-ribose) polymerase activity,
and inflammation (tumor necrosis factor- and interleukin-1) in
the kidneys of mice, associated with marked histopathological
damage and impaired renal function (elevated serum blood urea
nitrogen and creatinine levels) 72 h after the administration of the
drug. Treatment of mice with cannabidiol markedly attenuated
the cisplatin-induced oxidative/nitrosative stress, inflammation,
and cell death in the kidney, and it improved renal function.
Thus, our results suggest that cannabidiol may represent a
promising new protective strategy against cisplatin-induced
nephrotoxicity.
