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 (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.

• Authors: Hao Pan, Partha Mukhopadhyay, Mohanraj Rajesh, Vivek Patel, Bani Mukhopadhyay, Bin Gao, György Haskó, Pál Pacher
• Journal: The Journal of pharmacology and experimental therapeutics (J Pharmacol Exp Ther) Vol. 328 Issue 3 Pg. 708-14 (Mar 2009) ISSN: 1521-0103 [Electronic] United States
• PMID: 19074681 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Cannabidiol
• NADH, NADPH Oxidoreductases
• NADPH Oxidase 1
• NADPH Oxidase 4
• NADPH Oxidases
• NOX1 protein, mouse
• Nox4 protein, mouse
• Caspase 3
• Caspase 7
• Cisplatin

Topics

• Animals
• Cannabidiol (pharmacology)
• Caspase 3 (drug effects, metabolism)
• Caspase 7 (drug effects, metabolism)
• Cell Death (drug effects)
• Cisplatin (antagonists & inhibitors, toxicity)
• Gene Expression Regulation, Enzymologic (drug effects)
• Inflammation (prevention & control)
• Kidney (drug effects, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• NADH, NADPH Oxidoreductases (genetics)
• NADPH Oxidase 1
• NADPH Oxidase 4
• NADPH Oxidases (drug effects, genetics)
• Oxidative Stress (drug effects)