Abstract
Cisplatin is a highly effective antineoplastic agent used to treat solid tumors. Unfortunately,
the administration of this drug leads to significant side effects, including ototoxicity,
nephrotoxicity, and neurotoxicity. This review addresses the mechanisms of cisplatin-induced
ototoxicity and various strategies tested to prevent this distressing adverse effect.
The molecular pathways underlying cisplatin ototoxicity are still being investigated.
Cisplatin enters targeted cells in the cochlea through the action of several transporters.
Once it enters the cochlea, cisplatin is retained for months to years. It can cause
DNA damage, inhibit protein synthesis, and generate reactive oxygen species that can
lead to inflammation and apoptosis of outer hair cells, resulting in permanent hearing
loss. Strategies to prevent cisplatin ototoxicity have utilized antioxidants, transport
inhibitors, G-protein receptor agonists, and anti-inflammatory agents. There are no
FDA-approved drugs to prevent cisplatin ototoxicity. It is critical that potential
protective agents do not interfere with the antitumor efficacy of cisplatin.
Keywords
cisplatin - otoprotection - antioxidants - apoptosis - cochlea
