Cisplatin Nephrotoxicity: New Insights in an Old Problem

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Ioannis Koulouridis Efstathios Koulouridis


Cis-diamino-dichloro platinum is one of the most widely used antineoplastic drugs. It is used therapeutically in 10-20% of all cancers. It is active against a variety of solid tumors such as head, neck, lungs, ovaries, cervix, bladder, etc. The therapeutic use of the drug is combined with significant toxicities such as: neurotoxicity (85-95%), ototoxicity (23-50%), nephrotoxicity (30%), gastrotoxicity and bone marrow suppression.

Nephrotoxicity is a limiting condition since repeated episodes of acute kidney injury may lead to chronic kidney disease which then develops regardless of drug discontinuation. Unfortunately, nephrotoxicity and antineoplastic activity share common molecular mechanisms at the cellular level. Therefore, any attempt to reduce nephrotoxicity implies a reduction in the antineoplastic effect.

Continuing investigation of the mechanisms underlying cisplatin nephrotoxicity upon molecular level has provided an enormous amount of knowledge concerning accumulation of the drug in renal epithelial cells, cellular damage via destruction of cellular organelles and cellular proteins as well as induction of repair and rescue mechanisms such as autophagy toward the improvement of cell survival. All these metabolic pathways are currently candidates for therapeutic intervention. Moreover, new therapeutic approaches based upon natural derivatives such as phytochemicals are under laboratory investigation hopping to add more effective treatments in cisplatin nephrotoxicity.  

In the present review we analyze the mechanisms of drug-induced cellular damage, the evidence so far, and developments in the effort to reduce nephrotoxicity without loss of drug activity.

Keywords: cisplatin, nephrotoxicity, autophagy, apoptosis, p53 protein, phytochemicals

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KOULOURIDIS, Ioannis; KOULOURIDIS, Efstathios. Cisplatin Nephrotoxicity: New Insights in an Old Problem. Medical Research Archives, [S.l.], v. 10, n. 3, mar. 2022. ISSN 2375-1924. Available at: <>. Date accessed: 23 july 2024. doi:
Research Articles


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