Protective role of bilberry extract against Cisplatin induced ototoxicity in rats

Abstract

To investigate the potential preventive effect of bilberry extract in cisplatin-induced ototoxicity. Thirty-five 3-3.5-month healthy adult female Sprague-Dawley rats were randomly divided into three groups and treated as follows: Both, group 1 (n = 10) and group 2 (n = 15) subjects received a single dose of 12 mg/kg cisplatin intraperitoneally; while in group 2, bilberry extract was also administered via gavage feeding for 15 days. Group 3 (n = 10), received no cisplatin or bilberry extract. Baseline distortion product otoacoustic emissions testing were performed in all subjects prior to administration of any medication. The test was repeated at 15th day following administration of any medication. The distortion product otoacoustic emissions were evaluated at 1.5, 2, 3, 4, 5, 6, 7, 8, 10 and 12 kHz. Histopathological changes in the cochlea of rats were observed by light microscopy. There was no statistically significant difference in apical turn between three groups but there was a statistically significant difference in basal and mid turn external ciliated cells number. Stria vascularis changes were statistically significant between three groups. The median score for stria vascularis injury and spiral ganglion cells changes were significantly greater in group 1 than in group 2. The initial distortion product otoacoustic emissions measurement results gave similar statistically insignificant values in the three groups (p > 0.05). In contrast to initial measurements statistically significant differences were recorded between day 0 and 15 otoacoustic thresholds (p < 0.05). Bilberry extract group had a significantly higher DP-gram except for 1.5 and 2 kHz frequencies when compared to cisplatin group. The analyses of the results revealed statistically significant differences between two groups (p < 0.05), suggesting that bilberry extract had shown a protective effect against cisplatin ototoxicity. The results of our study revealed that treatment with bilberry extract affords significant protection to the cochlea from cisplatin toxicity and thus, oral experimental dose of bilberry extract administration may have a protective effect against cisplatin ototoxicity in rats.

Keywords: Bilberry extract; Cisplatin; Ototoxicity.

Fig. 1

Comparison of distortion product-evoked otoacoustic emission measurements amplitudes for study groups at 15th day

Fig. 2

Fluorescence microscopy sections of external ciliated cells of study groups crosssectional area through the basal turn from a control group, b bilberry group, c cisplatin group. Greatest epithelial degeneration was observed in cisplatin group (hematoxylin & eosin, ×400)

Fig. 3

Comparison of external ciliated cells numbers in study groups

Fig. 4

Cross-sectional area of stria vascularis in a control group, b bilberry group showing stria vascularis slightly thickened, marginal cell blebbing and cytoplasmic vacuolization, c cisplatin group showing highly fragmented irregular cytoplasm and nuclei-degenerating cells (hematoxylin & eosin, ×400)

Fig. 5

a Normal appearance of spiral ganglion cells in control group, b vacuolization and nuclear degeneration are seen in bilberry group, c showing eosinophilic cytoplasm of spiral ganglion cells; spiral ganglion cells nuclei are not seen even in areas that can be viewed with the severe degeneration in cisplatin group (hematoxylin & eosin, ×400)