PT  - JOURNAL ARTICLE
AU  - Hao Pan
AU  - Partha Mukhopadhyay
AU  - Mohanraj Rajesh
AU  - Vivek Patel
AU  - Bani Mukhopadhyay
AU  - Bin Gao
AU  - György Haskó
AU  - Pál Pacher
TI  - Cannabidiol Attenuates Cisplatin-Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death
AID  - 10.1124/jpet.108.147181
DP  - 2009 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 708--714
VI  - 328
IP  - 3
4099  - http://jpet.aspetjournals.org/content/328/3/708.short
4100  - http://jpet.aspetjournals.org/content/328/3/708.full
SO  - J Pharmacol Exp Ther2009 Mar 01; 328
AB  - 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-α and interleukin-1β) 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. U.S. Government work not protected by U.S. copyright