Molecular mechanisms of cisplatin-induced nephrotoxicity: a balance on the knife edge between renoprotection and tumor toxicity.

Volarevic, Vladislav; Djokovic, Bojana; Jankovic, Marina Gazdic; Harrell, C Randall; Fellabaum, Crissy; Djonov, Valentin; Arsenijevic, Nebojsa (2019). Molecular mechanisms of cisplatin-induced nephrotoxicity: a balance on the knife edge between renoprotection and tumor toxicity. Journal of biomedical science, 26(1), p. 25. BioMed Central 10.1186/s12929-019-0518-9

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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.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Anatomy > Topographical and Clinical Anatomy

UniBE Contributor:

Djonov, Valentin Georgiev

ISSN:

1423-0127

Publisher:

BioMed Central

Language:

English

Submitter:

David Christian Haberthür

Date Deposited:

28 Jan 2021 09:10

Last Modified:

31 Jan 2021 02:57

Publisher DOI:

10.1186/s12929-019-0518-9

PubMed ID:

30866950

Uncontrolled Keywords:

Acute kidney injury Apoptosis Cisplatin Inflammation Nephrotoxicity

BORIS DOI:

10.48350/149218

URI:

https://boris.unibe.ch/id/eprint/149218

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