Cannabidiol Attenuates Cisplatin-Induced Nephrotoxicity by Decreasing Oxidative/Nitrosative Stress, Inflammation, and Cell Death
- 12 December 2008
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Journal of Pharmacology and Experimental Therapeutics
- Vol. 328 (3), 708-714
- https://doi.org/10.1124/jpet.108.147181
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-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.Keywords
This publication has 43 references indexed in Scilit:
- Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cellsMolecular Cancer Therapeutics, 2007
- Cannabidiol arrests onset of autoimmune diabetes in NOD miceNeuropharmacology, 2007
- Cannabidiol attenuates high glucose-induced endothelial cell inflammatory response and barrier disruptionAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Nitric Oxide and Peroxynitrite in Health and DiseasePhysiological Reviews, 2007
- The Endocannabinoid System as an Emerging Target of PharmacotherapyPharmacological Reviews, 2006
- Antitumor Activity of Plant Cannabinoids with Emphasis on the Effect of Cannabidiol on Human Breast CarcinomaJournal of Pharmacology and Experimental Therapeutics, 2006
- Cellular processing of platinum anticancer drugsNature Reviews Drug Discovery, 2005
- The nonpsychoactive component of marijuana cannabidiol modulates chemotaxis and IL-10 and IL-12 production of murine macrophages both in vivo and in vitroJournal of Neuroimmunology, 2005
- Meetings and Conferences · Tagungen und KongresseOncology Research and Treatment, 1998
- Adverse effects of anti-tumor drug, cisplatin, on rat kidney mitochondria: Disturbances in glutathione peroxidase activityBiochemical and Biophysical Research Communications, 1989