Neurotrophic factors can reduce cisplatin-induced ototoxic damage in vitro

Cisplatin is widely used for the treatment of head and neck cancer, but side effects such as hearing loss and deafness are common. In this study the neurotrophic factors BDNF, GDNF and EPO as well as their combinations should be investigated regarding their otoprotective potential.

From the inner ear of neonatal rats (p3-p5), the organ of Corti (OC) was isolated and cultured for 48h. Neurotrophic factors at various concentrations were added to the culture medium (BNDF brain-derived neurotrophic factor: 50 nM, EPO erythropoietin: 5 nM, GDNF glial cell-derived neurotrophic factor: 50 nM, 100 nM, 200 nM). Cisplatin (20µM) was added after 24h, after a further 24h the OCs were fixed, stained and analyzed separately for apical, medial and basal fragments. The number of morphologically intact inner (IHC) and outer (OHC) hair cells as well as the neurites in the area of the peripheral process were determined.

The addition of 20µM cisplatin induced a significant reduction (p < 0.001) of the IHC and OHC over the entire area of the cochlea compared to control. However, cisplatin administration did not result in significant changes in the number of neurites. None of the tested neurotrophic factors showed a negative effect on hair cells or neurites.

While the addition of BNDF or EPO alone did not affect cisplatin toxicity compared to culture without the addition of the factors, BDNF + EPO-treated cultures had less cisplatin damage, particularly in the apical area of IHC.

The addition of 100 nM GNDF in particular protected the OHC over the entire area of the cochlea. This effect was not so pronounced in IHC.

This study demonstrates the otoprotective potential of the investigated neurotrophic factors. In further experiments, the mechanisms of otoprotection will now be investigated.