Correlation between signal transducer and activator of transcription 1 (STAT 1), vascular endothelial growth factor (VEGF), and signal to noise ratio (SNR) value in otoacoustic emission (OAE) examination on organ of Corti cochlea due to cisplatin
By
Nelfi Disya Amalia Lubis
,
Nelfi Disya Amalia Lubis
Department of Otorhinolaryngology, Faculty of Medicine, Universitas Sumatera Utara,
Medan Sumatera Utara, Indonesia
Aim To assess the cochlear damage caused by cisplatin in the rat cochlea based on decreased signal to noise ratio (SNR) values on otoacoustic emission (OAE) examination and increased expression of signal transducer and activator of transcription 1 (STAT 1) and vascular endothelial growth factor (VEGF) on immunohistochemical examination. Methods Twenty-four Rattus norvegicus were divided into 4 groups and injected with 8 mg/kgBW of cisplatin intraperitoneally except for control group. The SNR on OAE examination were checked before the treatment and on day 3, 4, and 7 after the treatment. The cochleas were stained immunohistochemically, followed by assessment of the cochlear organ of Corti damage based on STAT 1 and VEGF expression. Results A decrease in the mean of SNR value was found in accordance with the length of cisplatin exposure. The STAT 1 and VEGF expression increased with duration of cisplatin exposure. A correlation was found between SNR values, STAT 1, and also VEGF expression (p<0.05). Conclusion An increase of STAT 1 and VEGF expression influences cochlear damage due to cisplatin administration. There was a correlation between STAT 1 and VEGF expression with SNR values in the cochlear organ of Corti of Rattus norvegicus exposed to cisplatin.
Paken J, Govender CD, Pillay M, Sewram V. A review of cisplatin-associated ototoxicity. Semin Hear. 2019;40:108–21.
2.
Rybak LP, Ramkumar V, Mukherjea D. Ototoxicity of non-aminoglycoside antibiotics. Front Neurol. 2021;12(652674).
3.
Ganesan P, Schmiedge J, Manchaiah V, Swapna S, Dhandayutham S, Kothandaraman PP. Ototoxicity: a challenge in diagnosis and treatment. J Audiol Otol. 2018;22:59–65.
4.
Ramkumar V, Mukherjea D, Dhukhwa A, Rybak LP. Oxidative stress and inflammation caused by cisplatin ototoxicity. Antioxidants. 2021;10(1919).
5.
Rybak LP, Mukherjea D, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and prevention. Semin Hear. 2019;40:197–204.
6.
Rybak LP, Mukherjea D, Jajooo S, Ramkumar V. Cisplatin ototoxicity and protection: clinical and experimental studies. Tohoku J Exp Med. 2009;219:177–86.
7.
Sheth S, Mukherjea D, Rybak LP, Ramkumar V. Mechanisms of cisplatin-induced ototoxicity and otoprotection. Front Cell Neurosci. 2017;11(338).
8.
Zhang W, Xiong H, Pang J, Su Z, Lai L, Lin H, et al. Nrf2 activation protects auditory hair cells from cisplatin-induced ototoxicity independent on mitochondrial ROS production. Toxicol Lett. 2020;331:1–10.
9.
Deavall DG, Martin EA, Horner JM, Roberts R. Drug-induced oxidative stress and toxicity. J Toxicol. 2012;2012(645460).
Shetty S, Bhandary SK, Bhat V, Aroor R, Shety J, Dattatreya T. Role of otoacoustic emission in early detection of cisplatin induced ototoxicity. Indian J Otolaryngol Head Neck Surg. 2022;74:164–9.
12.
Sanli A, Aydin S, Sarisoy ZA, Paksoy M, Ayduran E, Çelebi Erdivanli Ö. The protective effect of dexamethasone and lactate against cisplatin-induced ototoxicity. Turk J Med Sci. 2011;41:467–74.
13.
Shomer NH, Allen-worthington KH, Hickman DL, Jonnalagadda M, Newsome JT, Slate AR, et al. Review of rodent euthanasia methods. J Am Assoc Lab Anim Sci. 2020;59:242–53.
14.
Czogalla B, Kahaly M, Mayr D, Schmoekel E, Niesler B, Kolben T, et al. Interaction of ERα and NRF2 impacts survival in ovarian cancer patients. Int J Mol Sci. 2019;20(112).
15.
Cakil B, Basar FS, Atmaca S, Cengel SK, Tekat A, Tanyeri Y. The protective effect of ginkgo biloba extract against experimental cisplatin ototoxicity: animal research using distortion product otoacoustic emissions. J Laryngol Otol. 2012;126:1097–101.
16.
Gündoğdu R, Erkan M, Aydin M, Sönmez MF, Vural A, Kökoğlu K, et al. Assessment of the effectiveness of querctin on cisplatin-induced ototoxicity in rats. J int Adv Otol. 2019;15:229–36.
17.
Somdaş MA, Güntürk I, Balcioğlu E, Avci D, Yazici C, Özdamar S. Protective effect of N-acetylcysteine against cisplatin ototoxicity in rats: a study with hearing tests and scanning electron microscopy. Braz J Otorhinolaryngol. 2020;86:30–7.
18.
Perše M, Večerić-Haler Ž. Cisplatin-induced rodent model of kidney injury: characteristics and challenges. Biomed Res Int. 2018;2018(1462802).
19.
Mahmoud AA, Abdel-Aziz HO, Elbadr M, Elbadre H. Effect of nicotine on stat 1 pathway and oxidative stress in rat lungs. Rep Biochem Mol Biol. 2021;10:429–34.
20.
Bodmer D, Kern P, Bachinger D, Naldi AM, Huaman SL. STAT1 Deficiency predisposes to spontaneous otitis media. PLoS One. 2020;15:1–15.
21.
Kros CJ, Steyger PS. Aminoglycoside and cisplatininduced ototoxicity: mechanisms and otoprotective strategies. Vol. 9:a033548. 2019.
22.
Baghal-Sadriforoush S, Bagheri M, Abdi Rad I, Sotoodeh Nejadnematalahi F. PI3K inhibition sensitize the cisplatin-resistant human ovarian cancer cell OVCAR3 by induction of oxidative stress. Rep Biochem Mol Biol. 2022;10:675–85.
23.
Jiang P, Ray A, Rybak LP, Brenner M. Role of STAT 1 and oxidative stress in gentamicin-induced hair cell death in organ of corti. Otol Neurotol. 2016;37:1449–56.
24.
Levano S, Bodmer D. Loss of STAT 1 protects hair cells from ototoxicity through modulation of STAT 3, c-Jun, Akt, and autophagy factors. Cell Death Dis. 2015;6:e2019.
25.
Lin MT, Ko JL, Liu TC, Chao PT, Ou CC. Protective effect of D-Methionine on body weight loss, anorexia, and nephrotoxicity in cisplatin-induced chronic toxicity in rats. Integr Cancer Ther. 2018;17:813–24.
26.
Clinkard D, Amoodi H, Kandasamy T, Grewal AS, Chen S, Qian W, et al. Changes in the cochlear vasculature and vascular endothelial growth factor and its receptors in the aging c57 mouse cochlea. ISRN Otolaryngol. 2013;2013(4306).
The statements, opinions and data contained in the journal are solely those of the individual authors and contributors and not of the publisher and the editor(s). We stay neutral with regard to jurisdictional claims in published maps and institutional affiliations.
,
