Intraperitoneal curcumin and vitamin E combination for the treatment of cisplatin-induced ototoxicity in rats.
BACKGROUND
Cisplatin ototoxicity is characterized by irreversible, progressive, bilateral sensorineural hearing loss at high frequencies, accompanied by tinnitus. The aim of this study is to demonstrate the protective action of curcumin alone or in combination with vitamin E against cisplatin-induced ototoxicity in animal models.


METHODS
The study included 42 rats. Experimental animals were randomized into 6 groups. In the first group, intra-peritoneal cisplatin was administered alone. In the second group, intra-peritoneal cisplatin and curcumin were administered together. In the third group, intra-peritoneal cisplatin and vitamin E were administered together. In the fourth group, intra-peritoneal cisplatin was administered together with curcumin in combination with vitamin E. In the fifth group, intra-peritoneal curcumin was administered alone. The sixth group was sacrificed directly without administration of any drugs. A distortion product otoacoustic emission (DPOAE) test was applied to both ears of all experimental animals. Curcumin was administered 1 h before cisplatin treatment continued for three successive days. Vitamin E was administered only as a single dose 30 min prior to cisplatin. All animals were sacrificed following DPOAE testing on the 5th day of cisplatin administration. Histopathological findings included a TUNEL (TdT-mediated deoxyuridine triphosphate nick end-labeling) assay, and the percentage of apoptotic cells was calculated. DPOAE values and the percentage of apoptotic cells were compared before and after treatment and between experimental groups.


RESULTS
In Group 1, DPOAE values were significantly decreased at all frequencies (3000 Hz, 4000 Hz and 6000 Hz; P < 0.05). In Groups 2, 3, 4 and 5 there was no significant difference between the pre- and post-treatment DPOAE results (p > 0.05). Apoptotic index values were lower in all treatment groups compared to the cisplatin group, however the difference was only statistically significant in group 3 (p = 0.009).


CONCLUSIONS
In rats, cisplatin ototoxicity can be prevented with curcumin or curcumin-vitamin E combination.
Ahi Evran University Training and Research Hospital, Department of Otorhinolaryngology, Kırşehir, Turkey. Electronic address: harun_soyalic@hotmail.com.
Harun
H
Soyalıç
Gaziosmanpaşa University, Department of Histology and Embryology, Tokat, Turkey.
Fikret
F
Gevrek
Antalya Training and Research Hospital, Department of Otorhinolaryngology, Antalya, Turkey.
Sema
S
Koç
Ahi Evran University Training and Research Hospital, Department of Otorhinolaryngology, Kırşehir, Turkey.
Mustafa
M
Avcu
Ahi Evran University Training and Research Hospital, Department of Otorhinolaryngology, Kırşehir, Turkey.
Mehmet
M
Metin
Katip Çelebi University, Atatürk Training and Research Hospital, Department of Otorhinolaryngology, İzmir, Turkey.
İbrahim
İ
Aladağ
D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity*; D004396:Coloring Agents; D003474:Curcumin / Q000494:pharmacology*; D004359:Drug Therapy, Combination; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced / Q000188:drug therapy*; D007274:Injections, Intraperitoneal; D008297:Male; D009925:Organ of Corti / Q000187:drug effects / Q000473:pathology; D017084:Otoacoustic Emissions, Spontaneous / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014012:Tinnitus; D014810:Vitamin E / Q000494:pharmacology*
D000970:Antineoplastic Agents; D000975:Antioxidants; D004396:Coloring Agents; D014810:Vitamin E; D003474:Curcumin; D002945:Cisplatin
Apoptosis; Cisplatin; Curcumin; Distortion product otoacoustic emission; Ototoxicity; Vitamin E