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Levosimendan ameliorates cisplatin-induced ototoxicity: Rat model
Mustafa Sitki Gozeler1, Fazile Nur Ekinci Akdemir2, Serkan Yildirim3
1Ataturk University, Faculty of Medicine, Department of Otorhinolaryngology, Erzurum, Turkey.
International Journal of Pediatric Otorhinolaryngology
|April 13, 2019
Summary
Levosimendan protects hearing from cisplatin-induced ototoxicity in rats by reducing oxidative stress and apoptosis. This study demonstrates levosimendan
Area of Science:
- Ototoxicity research
- Cancer therapeutics
- Pharmacology
Background:
- Cisplatin is a vital chemotherapy drug with dose-limiting toxicities, including ototoxicity.
- Ototoxicity significantly impairs patients' quality of life, necessitating protective strategies.
- Levosimendan's potential protective effects against cisplatin-induced ototoxicity require investigation.
Purpose of the Study:
- To evaluate the protective effect of levosimendan against cisplatin-induced ototoxicity in a rat model.
- To assess functional, biochemical, and histopathological changes associated with cisplatin and levosimendan treatment.
Main Methods:
- 24 female Sprague Dawley rats were divided into four groups: Control, Cisplatin, Levosimendan, and Cisplatin + Levosimendan.
- Distortion product otoacoustic emissions (DPOAE) were used for functional hearing assessment.
- Biochemical markers (MDA, SOD, GPx) and histopathological analysis (Caspase 3, 8-OHdG) of cochlear tissue were performed.
Main Results:
- Cisplatin induced significant cochlear oxidative stress (increased MDA, decreased SOD/GPx) and hearing impairment (reduced SNR).
- Levosimendan treatment significantly reduced MDA levels and increased SOD/GPx activities in cisplatin-treated rats.
- Levosimendan preserved cochlear structure and reduced Caspase 3 and 8-OHdG immunopositivity, indicating reduced apoptosis and cellular damage.
Conclusions:
- Levosimendan demonstrates significant protective effects against cisplatin-induced ototoxicity in rats.
- Levosimendan mitigates hearing loss by reducing oxidative stress and apoptosis in the cochlea.
- These findings suggest levosimendan as a potential therapeutic agent to prevent cisplatin-related hearing damage.
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