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Systematic Review Article

The Chemoprotective Potentials of Alpha-lipoic Acid Against Cisplatin-induced Ototoxicity: A Systematic Review


Ghaidaa Raheem Al-Awsi, Uzma Arshed, Anam Arif, Andrés Alexis Ramírez-Coronel, Muataz S. Alhassan, Yasser Fakri Mustafa, Ferry Fadzlul Rahman, Rahman S. Zabibah, Jitendra Gupta, Muhammad Shahid Iqbal, Acim Heri Iswanto and Bagher Farhood*   Pages 1 - 16 ( 16 )


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.


Cancer, cisplatin, chemotherapy, ototoxicity, alpha-lipoic acid, systematic review.


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