ArticleCell death & disease2013
A combination of cilostazol and Ginkgo biloba extract protects against cisplatin-induced Cochleo-vestibular dysfunction by inhibiting the mitochondrial apoptotic and ERK pathways.
Article in Cell death & disease, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 36 citations in OpenAlex.
- Pragmatic open-label clinical trial investigating the treatment effects of Ginkgo biloba extract EGb 761 on patients with vertigo and dizziness of various aetiologies.Frontiers in pharmacology · 2026Trial
- The efficacy and safety of systemic injection of Ginkgo biloba extract, EGb761, in idiopathic sudden sensorineural hearing loss: a randomized placebo-controlled clinical trial.European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery · 2016Trial
- Ginkgo biloba L. in preventing cardiovascular disease: pharmacological effects, mechanism of action, and therapeutic potential.Acta pharmacologica Sinica · 2026Review
- Vestibular hair cell redundancy and the critical requirement of type I cells for balance maintenance.Cellular and molecular life sciences : CMLS · 2026Article
- Effects ofNutrients · 2024Article
- FDA-Approved Tedizolid Phosphate Prevents Cisplatin-Induced Hearing Loss Without Decreasing Its Anti-tumor Effect.Journal of the Association for Research in Otolaryngology : JARO · 2024Article
- Unveiling the Role of Oxidative Stress in Cochlear Hair Cell Death: Prospective Phytochemical Therapeutics against Sensorineural Hearing Loss.International journal of molecular sciences · 2024Review
- Cisplatin vestibulotoxicity: a current review.Frontiers in surgery · 2024Review
- Age-related hearing loss and its potential drug candidates: a systematic review.Chinese medicine · 2023Review
- Mechanistic Protective Effect of Cilostazol in Cisplatin-Induced Testicular Damage via Regulation of Oxidative Stress and TNF-α/NF-κB/Caspase-3 Pathways.International journal of molecular sciences · 2023Article
- Progress in protecting vestibular hair cells.Archives of toxicology · 2021Review
- Sirtuin-3 Protects Cochlear Hair Cells Against Noise-Induced DamageFrontiers in cell and developmental biology · 2021Article
- Ginkgo biloba extract improves cognitive function and increases neurogenesis by reducing Aβ pathology in 5×FAD mice.American journal of translational research · 2021Article
- Anti-Cancer and Ototoxicity Characteristics of the Curcuminoids, CLEFMA and EF24, in Combination with Cisplatin.Molecules (Basel, Switzerland) · 2019Article
- The curcuminoid, EF-24, reduces cisplatin-mediated reactive oxygen species in zebrafish inner ear auditory and vestibular tissues.Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia · 2018Article
- Cilostazol Mediated Nurr1 and Autophagy Enhancement: Neuroprotective Activity in Rat Rotenone PD Model.Molecular neurobiology · 2018Article
- Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice.Scientific reports · 2016Article
- Early investigational drugs for hearing loss.Expert opinion on investigational drugs · 2015Review
- Bmi1 regulates auditory hair cell survival by maintaining redox balance.Cell death & disease · 2015Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cisplatin (cis-diammine-dichloroplatinum; CDDP) is an anticancer drug that induces significant hearing loss and balance dysfunction as side effects. Cilostazol (CS, 6-[4-(1-cyclohexyl-1H-tetrazol-5-yl) butoxy]-3, 4-dihydro-2-(1H)-quinolinone) has neuroprotective and antioxidant effects, whereas Ginkgo biloba extract (GbE) has preventive effects on CDDP-induced hearing loss in rats, and GbE enhances the antiatherogenic effect of CS by inhibiting the generation of reactive oxygen species (ROS). The purpose of this study was to investigate the effects of renexin (RXN), which contains GbE and CS, against CDDP-induced cochleo-vestibular dysfunction in rats and to elucidate the mechanism underlying the protective effects of RXN on auditory cells. Rats intraperitoneally injected with CDDP exhibited an increase in hearing threshold and vestibular dysfunction, which agreed with hair cell damage in the Organ of Corti and otoliths. However, these impairments were significantly prevented in a dose-dependent manner by pre- and co-treatment with RXN, and these preventive effects in RXN-treated rats were more prominent than those in GbE-treated rats. In a CDDP pharmacokinetic study, platinum concentration was very similar between CDDP-only treated and RXN+CDDP cotreated rats. RXN markedly attenuated CDDP-induced intracellular ROS and significantly reduced CDDP-activated expression of p-extracellular regulated kinase (ERK), BAX, cytochrome c, cleaved caspase-3 and cleaved poly (ADP-ribose) polymerase, but increased BCL-XL expression. These results show that RXN may have a synergistic effect by strongly protecting hearing and vestibular dysfunction induced by CDDP by inhibiting ROS production, mitochondrial pathways and the ERK pathway, without interfering with CDDP pharmacokinetics. Therefore, RXN could potentially be used to reduce CDDP-related hearing loss and dizziness.
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