Abstract
Purpose: Ototoxicity is one of the major adverse effects of cisplatin therapy which restrict
its clinical application. Alpha-lipoic acid administration may mitigate cisplatin-induced ototoxicity.
In the present study, we reviewed the protective potentials of alpha-lipoic acid against the
cisplatin-mediated ototoxic adverse effects.
Methods: Based on the PRISMA guideline, we performed a systematic search for the identification
of all relevant studies in various electronic databases up to June 2022. According to the inclusion
and exclusion criteria, the obtained articles (n=59) were screened and 13 eligible articles were finally
included in the present study.
Results: The findings of in-vitro experiments showed that cisplatin treatment significantly reduced
the auditory cell viability in comparison with the control group; nevertheless, the alpha-lipoic acid
co-administration protected the cells against the reduction of cell viability induced by cisplatin
treatment. Moreover, the in-vivo results of the auditory brainstem response (ABR) and distortion
product otoacoustic emission (DPOAE) tests revealed a decrease in DPOAE and an increase in
ABR threshold of cisplatin-injected animals; however, it was shown that alpha-lipoic acid co-treatment
had an opposite pattern on the evaluated parameters. Other findings demonstrated that cisplatin
treatment could significantly induce the biochemical and histopathological alterations in inner
ear cells/tissue; in contrast, alpha-lipoic acid co-treatment ameliorated the cisplatin-mediated biochemical
and histological changes.
Conclusion: The findings of audiometry, biochemical parameters, and histological evaluation
showed that alpha-lipoic acid co-administration alleviates the cisplatin-induced ototoxicity. The
protective role of alpha-lipoic acid against the cisplatin-induced ototoxicity can be due to different
mechanisms of anti-oxidant, anti-apoptotic, anti-inflammatory activities, and regulation of cell cycle
progression.
Keywords:
Cancer, cisplatin, chemotherapy, ototoxicity, alpha-lipoic acid, biochemical parameters.
[5]
Abdi Goushbolagh, N.; Abedi Firouzjah, R.; Ebrahimnejad Gorji, K.; Khosravanipour, M.; Moradi, S.; Banaei, A. Estimation of radiation dose-reduction factor for cerium oxide nanoparticles in MRC-5 human lung fibroblastic cells and MCF-7 breast-cancer cells. Artificial Cells, Nanomed., and Biotechnology., 2018, 46(sup3), S1215-s25.
[19]
Waissbluth, S.; Peleva, E.; Daniel, S.J. Platinum-induced ototoxicity: A review of prevailing ototoxicity criteria. Eur Arch Otorhinolaryngol., 2017, 274(3), 1187-1196.
[27]
Malińska, D.; Winiarska, K.; Metabolizmu, Z.R. Kwas liponowy–charakterystyka i zastosowanie w terapii* Lipoic acid: Characteristics and therapeutic application. Postepy Hig. Med. Dosw., 2005, 59, 535-543.
[37]
Moher, D.; Liberati, A.; Tetzlaff, J.; Altman, D.G. Preferred reporting items for systematic reviews and meta-analyses: The PRISMA statement. Annals Internal Med., 2009, 151(4), 264-9.
[75]
Werida, R.H.; Elshafiey, R.A.; Ghoneim, A.; Elzawawy, S.; Mostafa, T.M. Role of alpha-lipoic acid in counteracting paclitaxel- and doxorubicin-induced toxicities: a randomized controlled trial in breast cancer patients. Supportive Care Cancer, 2022, 30(9), 7281-7292.
[79]
Sogwagwa, N.; Davison, G.; Khan, S.; Solomon, W. P9. Correlation of radiation induced apoptosis with Bax and Bcl-2 protein expression. Physica Medica. European J. Med. Phy., 2016, 32, 163.
[92]
Olgun, Y.; Altun, Z.; Aktas, S.; Ercetin, P.; Kirkim, G.; Kiray, M. Molecular mechanisms of protective effect of resveratrol against cisplatinium induced ototoxicity. J. Int. Adv. Otol., 2013, 9(2), 145.
[97]
Casares, C.; Ramírez-Camacho, R.; Trinidad, A.; Roldán, A.; Jorge, E.; García-Berrocal, J.R. Reactive oxygen species in apoptosis induced by cisplatin: Review of physiopathological mechanisms in animal models. Eur. Arch. Otorhinolaryngol., 2012, 269(12), 2455-2459.
[102]
Simbula, G; Columbano, A; Ledda-Columbano, GM; Sanna, L; Deidda, M; Diana, A Increased ROS generation and p53 activation in alpha-lipoic acid-induced apoptosis of hepatoma cells. Apoptosis, 2007, 12(1), 113-23.
[125]
Alanazi, A.M.; Fadda, L.; Alhusaini, A.; Ahmad, R.; Hasan, I.H.; Mahmoud, A.M. Liposomal resveratrol and/or carvedilol attenuate doxorubicin-induced cardiotoxicity by modulating inflammation, oxidative stress and S100A1 in rats. Antioxidants, 2020, 9(2), 159.