The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats

Özdemir, Doğukan; Özgür, Abdulkadir; Kalkan, Yıldıray; Terzi, Suat; Tümkaya, Levent; Yılmaz, Adnan; Çeliker, Metin; Dursun, Engin

doi:10.1016/j.bjorl.2017.10.009

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Brazilian Journal of Otorhinolaryngology

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Original articles • Braz. j. otorhinolaryngol. 85 (1) • Jan-Feb 2019 • https://doi.org/10.1016/j.bjorl.2017.10.009 copy

The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats^☆ ☆ Please cite this article as: Özdemir D, Özgür A, Kalkan Y, Terzi S, Tümkaya L, Yılmaz A, et al. The protective effects of whortleberry extract against cisplatin-induced ototoxicity in rats. Braz J Otorhinolaryngol. 2019;85:55-62.

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Abstract

Introduction:

Cisplatin is one of the main chemotherapeutic agents used for the treatment of many types of cancer. However, ototoxicity, one of the most serious side effects of cisplatin, restricts its usage.

Objective:

We aimed to investigate the protective effects of whortleberry extract against cisplatin-induced ototoxicity by evaluating hearing and histopathological cochlear damage and by measuring the biochemical parameters affected byoxidative stress.

Methods:

Forty-eight male rats were included in the study after performing Distortion Product Otoacoustic Emission test to confirm that their hearing levels were normal. The rats were randomly divided into six groups: the control group, the sham group, and, which received only whortleberry extract, only cisplatin, cisplatin + 100 mg whortleberry extract, cisplatin + 200 mg whortleberry extract, respectively. Audiologic investigation was performed by performing the Distortion Product Otoacoustic Emission test at the beginning and at the eighth day of the study. Cardiac blood samples were collected for biochemical analysis, and the rats were sacrificed to obtain cochlear histopathological specimens on the eighth day.

Results:

The results revealed that whortleberry protects hearing against cisplatin-induced ototoxicity independent of the dose. However, high doses of whortleberry extract are needed to prevent histopathological degeneration and oxidative stress.

Conclusion:

The results obtained in this study show that whortleberry extract has a protective effect against cisplatin-induced ototoxicity.

KEYWORDS
Ototoxicity; Cisplatin; Whorleberry extract

Groups	Total antioxidant status Mean ± standard deviation (min-max)
Control group	1.12 mmoL Trolox equivalent/L ± 0.10 (0.96-1.60)
Sham group	1.11 mmoL Trolox equivalent/L ± 0.11 (0.98-1.27)
Whortleberry control group	1.45 mmoL Trolox equivalent/L ± 0.16 (1.12-1.60)
Cisplatin group	1.04 mmoL Trolox equivalent/L ± 0.05 (0.97-1.11)
Cisplatin + 100 mg/kg whortleberry group	1.21 mmoL Trolox equivalent/L ± 0.12 (1.01-1.36)
Cisplatin + 200 mg/kg whortleberry group	1.34 mmoL Trolox equivalent/L ± 0.03 (1.27-1.38)

Groups	Total oxidative stress Mean ± standard deviation (min-max)
Control group	7.40 µmoL H₂O₂ equivalent/L ± 1.56 (5.60-9.56)
Sham group	12.88 µmoL H₂O₂ equivalent/L ± 6.57 (6.48-23.76)
Whortleberry control group	10.71 µmoL H₂O₂ equivalent/L ± 4.21 (5.79-18.73)
Cisplatin group	22.49 µmoL H₂O₂ equivalent/L ± 10.73 (11.54-40.09)
Cisplatin + 100 mg/kg whortleberry group	18.90 µmoL H₂O₂ equivalent/L ± 5.38 (8.95-24.37)
Cisplatin + 200 mg/kg whortleberry group	14.67 µmoL H₂O₂ equivalent/L ± 7.56 (8.85-31.41)

Groups	Oxidative stress index Mean ± standard deviation (min-max)
Control group	6.72 ± 1.84 (4.55-9.96)
Sham group	11.66 ± 5.80 (5.50-20.96)
Whortleberry control group	7.41 ± 2.71 (3.71-11.93)
Cisplatin group	21.54 ± 9.94 (11.54-39.31)
Cisplatin + 100 mg/kg whortleberry group	16.02 ± 5.42 (6.73-23.14)
Cisplatin + 200 mg/kg whortleberry group	11.03 ± 5.76 (6.65-23.62)

Groups	Histopathological Blind Grading Mean ± standard deviation (min-max)
	Cytoplasmic vacuolization	Cellular degeneration	Dilatation	Apoptotic cell	Nerve degeneration
Control group	0.25 ± 0.46 (0-1)	0.13 ± 0.36 (0-1)	0.13 ± 0.36 (0-1)	0.63 ± 0.52 (0-1)	0.25 ± 0.46 (0-1)
Sham group	0.38 ± 0.52 (0-1)	0	0.25 ± 0.46 (0-1)	0.50 ± 0.53 (0-1)	0.25 ± 0.46 (0-1)
Whortleberry control group	0.75 ± 0.71 (0-2)	0.88 ± 0.99 (0-2)	0.75 ± 0.89 (0-2)	0.50 ± 0.53 (0-1)	0.38 ± 0.52 (0-1)
Cisplatin group	3.63 ± 0.52 (3-4)	3.13 ± 0.35 (3-4)	2.63 ± 0.74 (2-4)	3.00 ± 0.00 (3-3)	2.50 ± 0.53 (2-3)
Cisplatin + 100 mg/kg whortleberry group	1.75 ± 0.46 (1-2)	1.63 ± 0.52 (1-2)	1.75 ± 0.46 (1-2)	2.75 ± 0.46 (2-3)	2.13 ± 0.83 (1-3)
Cisplatin + 200 mg/kg whortleberry group	0.88 ± 0.64 (0-2)	0.88 ± 0.83 (0-2)	0.50 ± 0.53 (0-1)	1.00 ± 0.76 (0-2)	1.50 ± 0.76 (0-2)

Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Sede da Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico Facial, Av. Indianópolia, 1287, 04063-002 São Paulo/SP Brasil, Tel.: (0xx11) 5053-7500, Fax: (0xx11) 5053-7512 - São Paulo - SP - Brazil
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[1] * Corresponding author. E-mail:akozgur53@gmail.com (A. Özgür).