Authors:
Pan H, Mukhopadhyay P, Rajesh M, Patel V, Mukhopadhyay B, Gao B, Haskó G, Pacher P.
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 (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-alpha and interleukin-1beta) 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.