The Antiapoptotic Effect of Curcumin in the Fibroblast of the Cochlea in an Ototoxic Rat Model

Document Type : Original


1 Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, Universitas Sumatera Utara,, Medan 20155, Indonesia.

2 Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, Universitas Sumatera Utara, Medan 20155, Indonesia.

3 Department of Otorhinolaryngology-Head and Neck Surgery, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia.


This study aimed to show the potency of curcumin as an antiapoptotic agent that decreases the apoptotic index in the cochlea lateral wall in ototoxic rat models.
Materials and Methods:
A total of 24 Rattus norvegicus were divided into eight groups: Group 1 (control group), Group 2 (gentamicin (+)), Group 3 (gentamicin + curcumin 20 mg/day), Group 4 (gentamicin + curcumin 40 mg/day), Group 5 (gentamicin + curcumin 20 mg/day for 7 days), Group 6 (gentamicin + curcumin 40 mg/day for 7 days), Group 7 (curcumin 20 mg/day for 3 days + gentamicin), and Group 8 (curcumin 40 mg/day for 3 days + gentamicin). After the division, the rats were terminated in order to measure the apoptotic index using a terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay in the fibroblasts of the cochlea lateral walls. The data were analyzed using analysis of variance (ANOVA), and P  
Administration of gentamicin showed significant differences (P<0.05) in the apoptotic index. Groups undergoing curcumin treatment at a higher dose (200 mg/kg bw) and the prevention groups showed significant differences compared with groups not treated with curcumin
This study concluded that the apoptotic index can be decreased by curcumin and has a preventive benefit toward ototoxic rat models. The administration of curcumin depended on the dose and duration.


Main Subjects

1. Huth ME, Ricci AJ, Cheng AG. Mechanism of aminoglycoside ototoxicity and targets of hair cell protection. Int J Otolaryngol. 2011:1-19.
2. Petersen L, Rogers C. Aminoglycoside-induced hearing deficits of cochlea ototoxicity. South African Fam Pract. 2015;57:77–82.
3. Fetoni AR, Eramo SLM, Rolesi R, Troiani D, Paludetti G. Antioxidant treatment with coenzyme Q-ter in prevention of gentamycin ototoxicity in an animal model. Acta Otorhinolaryngol Ital. 2012; 32:103–110.
4. Alkahtani S, Alarifi SA, Al-Doaiss AA. Detection of apoptosis induced by gentamicin in rat hepatocytes. Int J Zool Res. 2009;5:161–70.
5. Selimoglu E. Aminoglycoside-induced ototoxicity. Curr Pharm Des. 2007; 13: 119–26.
6. Yu L, Fan Y, Ye G, Li J, Feng X, Lin K, et al. Curcumin inhibits apoptosis and brain edema induced by hypoxia-hypercapnia brain damage in rats models. Am J Med Sci. 2015; 6:521–5.
7. Bulku E, Stohns SJ, Cicero L, Brooks T, Halley H, Ray SD. Curcumin exposure modulates multiple pro-apoptotic and anti-apoptotic signaling pathways to antagonize acetaminophen-induced toxicity. Curr Neurovasc Res. 2012;9:58–71.
8. Ho C, Hsu YC, Lei CC, Mau SC, Shih YH, Lin CL. Curcumin rescues diabetic renal fibrosis by targeting superoxide-mediated wnt signaling pathways. Am J Med Sci. 2016;3:286–295.
9. Morsy MA, Moselhy MAE. Mechanism of the protective effects of curcumin against indomethacin-induced gastric ulcer in rats. Pharmacol. 2013;91:267–74.
10. Toydemir T, Kanter M, Erboga M, Oguz S, Erenoglu C. Antioxidative, antiapoptotic and proliferative effect of curcumin on liver regeneration after partial hepatectomy in rats. Toxicol Ind Health. 2015;31:162–72.
11. Sagit M, Somdas MA, Korkmaz F, Akcadag A. The ototoxic effect of intratympanic terbinafine applied in middle ear rats. J Otolaryngol Head Neck Surg. 2013;42(1):1-6.
12. Suzuki M, Ushio M, Yamasoba T. Time course of apoptotic cell death in guinea pig cochlea following intratympanic gentamicin application. Acta OtoLaryngol. 2008;128: 724–31.
13. Zhang W, Feng H, Gao Y, Sun L,Wang J, Li Y, et al. Role of pigment epithelium-derived factor (PEDF) in arsenic-induced cell apoptosis of  liver and brain in a rat model. Biol Trace Elem Res. 2013; 151: 269–76.
14. Fujioka M, Okamoto Y, Shinden S, Okano HJ, Okano H, Ogawa K, et al. Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall: A potential therapeutic target for sensorineural hearing loss. PLoS One. 2014;9(3):1-7.
15. Ding D, Jiang H, Salvi RJ. Mechanism of rapid sensory hair-cell death following co-administration of gentamicin and ethacrynic acid. Hearing Res. 2010;259:16–23.
16. Aktas C, Kanter M, Erboga M, Ozturk S. Anti-apoptotic effects of curcumin on cadmium-induced apoptosis in rat testes. Toxicolo Indust Health. 2012; 28:122–130.
17. Kurasawa T, Steyger PS. Intracellular mechanism of aminoglycoside-induced cytotoxicity. Integr Biol. 2011;3:879–86.
18. Motaghinejad M, Karimian M, Motaghinejad O, Shabab B, Yazdani I, Fatima S. Protective effect of various dosage of curcumin against morphine induced apoptosis and oxidative stress in rat isolated hippocampus. Pharmacol Rep. 2015; 67:230–5.
19. Fan J, Li X, Yan YW, Tian XH, Hou WJ, Tong H, et al. Curcumin attenuates rat thoracic aortic aneurysm formation by inhibition of the c-Jun N-terminal kinase pathway and apoptosis. Nutrition. 2012;28:1068–1074.
20. Yamaguchi T, Yoneyama M, Onaka Y, Imaizumi A, Ogita K. Preventive effect of curcumin and its highly bioavailable preparation on hearing loss induced by single or repeated exposure to noise: A comparative and mechanistic study. J Pharmacol Sci. 2017;134:225–33.
21. Fetoni AR, Eramo SLM, Paciello F, Rolesi R, Podda MV, Troiani D, et al. Curcuma longa (curcumin) decreases in vivo cisplatin –induced ototoxicity through heme oxygenase-1 induction. Otol Neurotol. 2014;35:e169–e77.