title: Evaluation of the protective effects of hesperetin against cisplatin-induced ototoxicity in a rat animal model.
abstract: OBJECTIVE
  We 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).
  
  
  METHODS
  Twenty-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 (12mg/kg) by intraperitoneal injection. Group CH received intraperitoneally cisplatin (12mg/kg) and hesperetin (20mg/kg). Group H was exposed to hesperetin (20mg/kg) intraperitoneally. The sham group (group S) received normal saline (6cc) 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.
  
  
  RESULTS
  There 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.
  
  
  CONCLUSIONS
  Hesperetin may prevent ototoxicity by increased antioxidant enzymes and reduced oxidant parameters and protected against apoptosis resulting from a proliferation of cochlear cells in CIO.
authors.affiliation: Department of Otorhinolaryngology, Canakkale Onsekiz Mart University, Faculty of Medicine, 17060 Canakkale, Turkey. Electronic address: medinekara@gmail.com.
authors.forename: Medine
authors.initials: M
authors.lastname: Kara
authors.affiliation: Department of Biochemistry, Medical Faculty of Canakkale Onsekiz Mart University, 17060 Canakkale, Turkey. Electronic address: hakanturkon@gmail.com.
authors.forename: Hakan
authors.initials: H
authors.lastname: Türkön
authors.affiliation: Department of Histology and Embryology, TrakyaUniversity, Faculty of Medicine, 22030 Edirne, Turkey. Electronic address: turankaraca@trakya.edu.tr.
authors.forename: Turan
authors.initials: T
authors.lastname: Karaca
authors.affiliation: Department of Otorhinolaryngology, Canakkale Onsekiz Mart University, Faculty of Medicine, 17060 Canakkale, Turkey. Electronic address: droguzguclu@hotmail.com.
authors.forename: Oğuz
authors.initials: O
authors.lastname: Güçlü
authors.affiliation: Department of Biochemistry, Medical Faculty of Canakkale Onsekiz Mart University, 17060 Canakkale, Turkey. Electronic address: dr_semauysal@hotmail.com.
authors.forename: Sema
authors.initials: S
authors.lastname: Uysal
authors.affiliation: Department of Otorhinolaryngology, Canakkale Onsekiz Mart University, Faculty of Medicine, 17060 Canakkale, Turkey. Electronic address: dr_mehmet_86@hotmail.com.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Türkyılmaz
authors.affiliation: Department of Histology and Embryology, TrakyaUniversity, Faculty of Medicine, 22030 Edirne, Turkey. Electronic address: selimdemirtas@yandex.com.
authors.forename: Selim
authors.initials: S
authors.lastname: Demirtaş
authors.affiliation: Department of Otorhinolaryngology, Canakkale Onsekiz Mart University, Faculty of Medicine, 17060 Canakkale, Turkey. Electronic address: sefaderekoy@gmail.com.
authors.forename: Fevzi Sefa
authors.initials: FS
authors.lastname: Dereköy
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000633:toxicity*; D003051:Cochlea / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D007758:Ear, Inner; D034381:Hearing Loss / Q000139:chemically induced / Q000503:physiopathology; D006569:Hesperidin / Q000494:pharmacology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D007274:Injections, Intraperitoneal; D008297:Male; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D059629:Signal-To-Noise Ratio; D013136:Spiral Ganglion / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D006569:Hesperidin; D002945:Cisplatin; C013015:hesperetin
keywords: Antioxidant; Apopitosis; Cisplatin; Hesperetin; Ototoxicity; Oxidative stress