- 作者: Vladislav Volarevic, Bojana Djokovic, Marina Gazdic Jankovic, C. Randall Harrell, Crissy Fellabaum, Valentin Djonov and Nebojsa Arsenijevic
- 作者服務機構: 1. Center for Molecular Medicine and Stem Cell Research, Faculty of Medical Sciences, University of Kragujevac, 69 Svetozar Markovic Street, Kragujevac, 34000, Serbia 2. Department of Genetics, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia 3. Regenerative Processing Plant, LLC, US Highway 19 N Palm Harbor, Palm Harbor, Florida, 34176, USA 4. Institute of Anatomy, University of Bern, 2 Baltzerstrasse, Bern, Switzerland
- 中文摘要:
- 英文摘要:
Background
Cisplatin (cis-diamminedichloroplatinum II, CDDP) is one of the most effective chemotherapeutic agents. However, its clinical use is limited due to the severe side effects, including nephrotoxicity and acute kidney injury (AKI) which develop due to renal accumulation and biotransformation of CDDP. The alleviation or prevention of CDDP-caused nephrotoxicity is currently accomplished by hydration, magnesium supplementation or mannitol-induced forced diuresis which is considered for high-dose CDDP-treated patients. However, mannitol treatment causes over-diuresis and consequent dehydration in CDDP-treated patients, indicating an urgent need for the clinical use of safe and efficacious renoprotective drug as an additive therapy for high dose CDDP-treated patients.
Main body
In this review article we describe in detail signaling pathways involved in CDDP-induced apoptosis of renal tubular cells, oxidative stress and inflammatory response in injured kidneys in order to pave the way for the design of new therapeutic approaches that can minimize CDDP-induced nephrotoxicity. Most of these molecular pathways are, at the same time, crucially involved in cytotoxic activity of CDDP against tumor cells and potential alterations in their function might mitigate CDDP-induced anti-tumor effects.
Conclusion
Despite the fact that many molecules were designated as potential therapeutic targets for renoprotection against CDDP, modulation of CDDP-induced nephrotoxicity still represents a balance on the knife edge between renoprotection and tumor toxicity. - 中文關鍵字:
- 英文關鍵字: Cisplatin, Nephrotoxicity, Acute kidney injury, Apoptosis, Inflammation