Evaluation of the Effect of Rosuvastatin on Cisplatin-induced Nephrotoxicity and Ototoxicity
Status:
Recruiting
Trial end date:
2021-08-01
Target enrollment:
Participant gender:
Summary
Cisplatin is an effective anti-cancer drug for the treatment of many solid tumors in humans.
Although the clinical response to cisplatin chemotherapy is encouraging, the nephrotoxicity
and ototoxicity of the drug makes it difficult to continue its administration in many cases.
Cisplatin nephrotoxicity occurs through several mechanisms, mainly through the transport and
accumulation of cisplatin into renal epithelial cells, injury to nuclear and mitochondrial
DNA, activation of multiple cell death pathways and initiation of inflammatory response.
Accordingly, several experimental strategies were developed to prevent this toxicity. For
example, drugs that reduced renal cisplatin accumulation such as organic cation transporter 2
(OCT2) and copper transporter (Ctr1) inhibitors, antioxidants, antiapoptotic and
anti-inflammatory agents were investigated. However, many of these drugs interfered with the
cytotoxic effects of cisplatin.
Statins are agents used for reducing plasma cholesterol through the inhibition of the enzyme
3- hydroxy-3- methylglutaryl coenzyme A (HMG-CoA) reductase. In addition, statins are also
proven to have pleiotropic, non-lipid dependent effects. These effects include
anti-inflammatory actions and reduction of oxidative stress. Based on animal studies
performed, statins have been shown to reduce the nephrotoxic effects of cisplatin in rats. In
addition, ongoing clinical trials are aiming to investigate the role of statins in the
protection against the ototoxicity of cisplatin as well. Our aim is to assess the protective
effect of statins on cisplatin-induced nephrotoxicity and ototoxicity in humans.