Evaluation of the Protective Effect of α-Lipoic Acid on Cisplatin Ototoxicity Using Distortion-Product Otoacoustic Emission Measurements

Özkul, Yılmaz; Songu, Murat; Başoğlu, Mehmet Sinan; Öztürkcan, Sedat; Katılmış, Hüseyin

doi:10.1097/scs.0000000000000881

Cited by 11 publications

(5 citation statements)

References 21 publications

(24 reference statements)

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“…In addition, the antioxidant effect of LA was shown to play a role in this prevention. In an in vivo study, administration of LA prevented cisplatin cytotoxicity and preserved hearing [18, 26]. In two studies using distortion product otoacoustic emissions or the auditory brainstem response, hearing was preserved in animals with hearing loss treated with LA, but these studies did not fully explain the mechanism of antioxidant activity of LA.…”

Section: Discussionmentioning

confidence: 99%

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway

et al. 2019

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The production of reactive oxygen species (ROS) by cisplatin is one of the major mechanisms of cisplatin-induced cytotoxicity. We examined the preventive effect of α-lipoic acid (LA) on cisplatin-induced toxicity via its antioxidant effects on in vitro and ex vivo culture systems. To elucidate the mechanism of the antioxidant activity of LA, NRF2 was inhibited using NRF2 siRNA, and the change in antioxidant activity of LA was characterized. MTT assays showed that LA was safe at concentrations up to 0.5 mM in HEI-OC1 cells and had a protective effect against cisplatin-induced cytotoxicity. Intracellular ROS production in HEI-OC1 cells was rapidly increased by cisplatin for up to 48 h. However, treatment with LA significantly reduced the production of ROS and increased the expression of the antioxidant proteins HO-1 and SOD1. Ex vivo, the organs of Corti of the group pretreated with LA exhibited better preservation than the group that received cisplatin alone. We also confirmed the nuclear translocation of NRF2 after LA administration, and that NRF2 inhibition decreased the antioxidant activity of LA. Together, these results indicate that the antioxidant activity of LA was through the activation of the NRF2/HO-1 antioxidant pathway.

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Section: Discussionmentioning

confidence: 99%

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway

et al. 2019

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“…Intraperitoneal application of cisplatin has been used in many hearing loss animal models (15,(33)(34)(35)(36). It has been shown that this application route leads to a high local concentration of cisplatin with a relatively low systemic absorption and toxicity (37,38).…”

Section: Figurementioning

confidence: 99%

Establishment of an optimized guinea pig model of cisplatin-induced ototoxicity

et al. 2023

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BackgroundCisplatin is among the most effective antineoplastic agents and has revolutionized the treatment of many cancer diseases. However, one of its serious side effects is a progressive and irreversible hearing loss, occurring in both adults and children. For the development of otoprotective therapies that prevent this side effect, cisplatin-induced hearing loss animal models are indispensable. Due to the high toxicity of cisplatin, the establishment of such animal models is a difficult and time-consuming task. Here we introduce the detailed protocol of a sophisticated guinea pig model with a sufficient and permanent hearing loss induced by cisplatin. This manuscript is intended to provide guidance in the development of future cisplatin guinea pig models which may reduce the mortality rate of the animals and help to gain more reproducible results.MethodsPigmented and unpigmented guineapigs were treated with an intravenous single application of 8 mg/kg cisplatin under general anesthesia. An extensive and long-term intensive care protocol consisting of scheduled application of fluids, antiemetics, analgesics, glucose and supportive feeding among others, was used to ensure wellbeing of the animals. Hearing tests were performed prior to and 5 days after cisplatin application. Animals were then euthanized.ResultsThe ABR audiometry 5 days after cisplatin application revealed a hearing threshold ranging from 70 dB to 90 dB in the frequencies from 1 kHz to 32 kHz respectively.All animals presented a good health condition despite the treatment with cisplatin.DiscussionThe introduced care protocol in this manuscript is intended to serve as a guidance for the establishment of a stable guinea pig model for short- and long-term investigation regarding the inner ear and its protection in the frame work of cisplatin-induced damage.

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“…Other protective drugs have been experimented in animal and human studies during the past few years; these include alpha-lipoic acid 61 , trichostatin A 62 , oxytocin 63 , resveratol 64 , hesperetin 65 and lutein 66 . However, data are preliminary and have not been confirmed.…”

Section: Current Pharmacological Approachesmentioning

confidence: 99%

Acquired sensorineural hearing loss in children: current research and therapeutic perspectives

Ralli

Rolesi

Anzivino

et al. 2017

Acta Otorhinolaryngol Ital

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La conoscenza dei meccanismi fisiopatologici delle condizioni responsabili dellipoacusia acquisita nei bambini, tra cui le infezioni virali e batteriche, lesposizione al rumore, lototossicità da chemioterapici ed antibiotici aminoglicosidici, è in costante aumento e sta portando ad un progressivo cambiamento della gestione diagnostica e clinica del bambino ipoacusico. Le infezioni virali rappresentano la causa più frequente di sordità infantile acquisita, seguita dalla tossicità di antibiotici e chemioterapici; mentre lesposizione al rumore, soprattutto negli adolescenti, rappresenta un fattore emergente. Le terapie farmacologiche protettive attualmente in uso includono steroidi, antiossidanti, antivirali; lefficacia degli antiossidanti è ancora in fase di conferma clinica anche se vi sono significative evidenze sperimentali, mentre i farmaci steroidei ed antivirali sono certamente validi seppur la loro tossicità sistemica rappresenti ancora un problema non chiarito per i quali la somministrazione locale potrebbe rappresentare una possibile evoluzione. Le prospettive di ricerca future includono luso di nanoparticelle per veicolare molecole direttamente nel sito di danno; inoltre, la terapia genica con linserimento di materiale genetico allinterno delle cellule per la cura di condizioni da alterazione del patrimonio genetico con la produzione di proteine normali, potrebbe svolgere un ruolo rilevante nella cura e soprattutto nella prevenzione delle sordità acquisite; infine, la terapia rigenerativa e limpianto delle cellule staminali, nonostante il loro ruolo nellorecchio interno sia ancora dibattuto, per le notevole limitazioni del loro impiego, potrebbe trovare un ruolo nei processi riparativi più che nella differenziazione in cellule sensoriali.

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Evaluation of the Protective Effect of α-Lipoic Acid on Cisplatin Ototoxicity Using Distortion-Product Otoacoustic Emission Measurements

Cited by 11 publications

References 21 publications

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway

α-Lipoic acid prevents against cisplatin cytotoxicity via activation of the NRF2/HO-1 antioxidant pathway

Establishment of an optimized guinea pig model of cisplatin-induced ototoxicity

Acquired sensorineural hearing loss in children: current research and therapeutic perspectives

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