Evaluation of the protective effects of hesperetin against cisplatin-induced ototoxicity in a rat animal model |
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| Institution: | 1. Department of Otorhinolaryngology, Canakkale Onsekiz Mart University, Faculty of Medicine, 17060 Canakkale, Turkey;2. Department of Biochemistry, Medical Faculty of Canakkale Onsekiz Mart University, 17060 Canakkale, Turkey;3. Department of Histology and Embryology, TrakyaUniversity, Faculty of Medicine, 22030 Edirne, Turkey;1. Doctoral Program in Biomedical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan;2. Department of Otolaryngology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan;1. Department of Biology, College of Natural Sciences, Kyungpook National University, Daegu, Republic of Korea;2. School of Life Sciences, KNU Creative BioResearch Group (BK21 plus project), Kyungpook National University, Daegu, Republic of Korea;3. Vestibulocochlear Research Center, Center for Metabolic Function Regulation and Department of Microbiology, Wonkwang University School of Medicine, Iksan, Jeonbuk, Republic of Korea;4. Department of Nuclear Medicine, Kyungpook National University School of Medicine, Daegu, Republic of Korea;5. Department of Internal Medicine, Research Institute of Aging and Metabolism, World Class University Program, Kyungpook National University School of Medicine, Daegu, Republic of Korea;6. Department of Otorhinolaryngology-Head and Neck Surgery, College of Medicine, Kyungpook National University, Daegu, Republic of Korea;1. Department of Otolaryngology-Head and Neck Surgery, Chosun University College of Medicine, Gwangju, South Korea;2. Department of Premedical Science, Chosun University College of Medicine, Gwangju, South Korea;3. Department of Anatomy, Chosun University College of Medicine, Gwangju, South Korea;1. Ataturk University, Faculty of Medicine, Department of Otorhinolaryngology, Erzurum, Turkey;2. Department of Nutrition and Dietetics, High School of Health, Agri Ibrahim Cecen University, Agri, Turkey;3. Ataturk University, Faculty of Veterinary, Department of Pathology, Erzurum, Turkey;4. Ataturk University, Faculty of Medicine, Department of Biochemistry, Erzurum, Turkey |
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| Abstract: | ObjectivesWe aimed to investigate the effects of hesperetin as a flavanon both histopathologically and immunohistochemically on cochlear apoptosis in a rat model of cisplatin-induced ototoxicity (CIO). The evaluation of the effects of hesperetin on cisplatin-induced hearing loss was performed using distortion product otoacoustic emission (DPOAE).MethodsTwenty-eight wistar albino rats were used in the current study. The rats were randomly divided into four groups with seven rats in each group. Group C was exposed to a single dose of cisplatin (12 mg/kg) by intraperitoneal injection. Group CH received intraperitoneally cisplatin (12 mg/kg) and hesperetin (20 mg/kg). Group H was exposed to hesperetin (20 mg/kg) intraperitoneally. The sham group (group S) received normal saline (6 cc) intraperitoneally. The measurements of DPOAE and signal-noise ratios (SNR) were performed before the treatment and again on the first and 6 days after administration of the drugs. Rats were sacrificed and cochleae were dissected 10 days after drug administration. The cochlear tissue was assessed in all groups by histopathologic, immunohistochemical and TUNEL assay. In addition, serum oxidative stress markers and antioxidant parameters were analyzed.ResultsThere was a significant difference between the basal value and the sixth day at frequencies 8.4, 9.6 and 9.96 for group C. We also found a significant difference between the first and sixth day at frequencies 7.2, 8.4, 9.6 and 9.96. On the 6th day, there were significant differences between C and S groups at all frequencies except 2.4. We showed a significant difference between C and H groups at frequencies 4.8, 6.0, 8.4, 9.6 and 9.96. There was also a significant difference between C and CH groups at frequencies 2.4, and 3.6. We found lower levels of oxidants and higher levels of antioxidants in CH group as compared to C group. C group had a significantly greater number of TUNEL-positive cells than did S, H and CH groups. The number of TUNEL-positive cells in CH group was higher than in S and H groups. There was a significant difference between the positive PCNA cells of CH group compared to S and H groups in spiral ganglion and stria vascularis. In addition, there were no positive PCNA cells in C group.ConclusionsHesperetin may prevent ototoxicity by increased antioxidant enzymes and reduced oxidant parameters and protected against apoptosis resulting from a proliferation of cochlear cells in CIO. |
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| Keywords: | Ototoxicity Cisplatin Hesperetin Apopitosis Antioxidant Oxidative stress |
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