In Vivo Evaluation of [Gly14]-Humanin's Protective Effect Against Cisplatin-Induced Ototoxicity
Abstract
Objectives: This study aimed to evaluate in vivo the potential protective effects of [Gly14]-humanin against cisplatin-induced ototoxicity (CIO) and its modulatory effects against oxidative stress, inflammatory, and apoptotic markers
Methods: Thirty-five male Balb/c mice were randomly divided into five groups: control, cisplatin, cisplatin + [Gly14]-humanin (3 mg/kg), cisplatin + (6 mg/kg), and vitamin E. Cisplatin (10 mg/kg, b.w.) was administered as a single dose. [Gly14]-humanin was administered intraperitoneally for 14 days. Biochemical analyses (Superoxide dismutase (SOD), glutathione (GSH), and malondialdehyde (MDA)), gene expression levels (TNF-α, IL-1β, IL-6, CASP-3, CASP-9, Bcl-2/Bax), and histopathological examinations (PARP1, PARP2 immunoreactivity) were performed in cochlear tissue samples to evaluate oxidative stress, inflammation, and apoptosis.
Results: Cisplatin decreased SOD and GSH levels and increased MDA levels in the cochlear tissue (P<0.05). With the application of [Gly14]-humanin, these parameters approached their normal levels. Cisplatin increased the values of pro-inflammatory and pro-apoptotic markers (TNF-α, IL-1β, IL-6, Caspase-3 (CAS-3), Caspase-9 (CAS-9)) significantly while reducing the Bcl-2/Bax ratio (P<0.05). [Gly14]-humanin administration reversed these effects in a dose-dependent manner. Histological analysis also revealed decreased PARP1 and PARP2 immunoreactivity in [Gly14]-humanin treated groups, comparable to the positive control (vitamin E).
Conclusions: The findings of this study show that [Gly14]-humanin exhibits important protective effects against CIO by attenuating oxidative stress, inflammation, and apoptosis in cochlear tissues. Further studies evaluating the clinical efficacy and reliability of [Gly14]-humanin are now needed.
Keywords
Ethical Statement
References
- 1. Tang Q, Wang X, Jin H, et al. Cisplatin-induced ototoxicity: Updates on molecular mechanisms and otoprotective strategies. Eur J Pharm Biopharm. 2021;163:60-71. doi: 10.1016/j.ejpb.2021.03.008.
- 2. Rybak LP, Whitworth CA, Mukherjea D, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res. 2007;226(1-2):157-67. doi: 10.1016/j.heares.2006.09.015.
- 3. Nagy JL, Adelstein DJ, Newman CW, Rybicki LA, Rice TW, Lavertu P. Cisplatin ototoxicity: the importance of baseline audiometry. Am J Clin Oncol. 1999;22(3):305-308. doi: 10.1097/00000421-199906000-00020.
- 4. Dai D, Chen C, Lu C, Guo Y, Li Q, Sun C. Apoptosis, autophagy, ferroptosis, and pyroptosis in cisplatin-induced ototoxicity and protective agents. Front Pharmacol. 2024;15:1430469. doi: 10.3389/fphar.2024.1430469.
- 5. Sheth S, Mukherjea D, Rybak LP, Ramkumar V. Mechanisms of Cisplatin-Induced Ototoxicity and Otoprotection. Front Cell Neurosci. 2017;11:338. doi: 10.3389/fncel.2017.00338.
- 6. Liu Z, Zhang H, Hong G, et al. Inhibition of Gpx4-mediated ferroptosis alleviates cisplatin-induced hearing loss in C57BL/6 mice. Mol Ther. 2024;32(5):1387-1406. doi: 10.1016/j.ymthe.2024.02.029.
- 7. Xu B, Li J, Chen X, Kou M. Puerarin attenuates cisplatin-induced apoptosis of hair cells through the mitochondrial apoptotic pathway. Biochim Biophys Acta Mol Cell Res. 2022;1869(4):119208. doi: 10.1016/j.bbamcr.2021.119208.
- 8. Lu X, Deng T, Dong H, et al. Novel Application of Eupatilin for Effectively Attenuating Cisplatin-Induced Auditory Hair Cell Death via Mitochondrial Apoptosis Pathway. Oxid Med Cell Longev. 2022;2022:1090034. doi: 10.1155/2022/1090034.
Details
Primary Language
English
Subjects
Otorhinolaryngology
Journal Section
Research Article
Authors
Murat Yaşar
0000-0003-3300-4430
Türkiye
Sedat Gökmen
0000-0002-4793-3030
Türkiye
Fatma Atalay
0000-0002-0344-1982
Türkiye
İrfan Çınar
0000-0002-9826-2556
Türkiye
Yusuf Aydin
*
0000-0002-0964-0405
Türkiye
Musa Tatar
0000-0002-5707-8832
Türkiye
Early Pub Date
December 9, 2025
Publication Date
January 4, 2026
Submission Date
October 15, 2025
Acceptance Date
November 24, 2025
Published in Issue
Year 2026 Volume: 12 Number: 1