Dexamethasone Protects Against Apoptotic Cell Death of Cisplatin-exposed Auditory Hair Cells In Vitro

Dinh, Christine T.; Chen, Si; Bas, Esperanza; Dinh, John; Goncalves, Stefania; Telischi, Fred; Angeli, Simón I.; Eshraghi, Adrien A.; Water, Thomas Van De

doi:10.1097/mao.0000000000000849

Cited by 17 publications

(12 citation statements)

References 12 publications

(33 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As mentioned earlier, glucocorticoids are used for their anti-inflammatory activity in the treatment of various types of sensorineural hearing loss, including being secondary to antitumor treatment with cisplatin. Glucocorticoids have intracellular receptors [10] and the mechanisms of action involved in otoprotection have been extensively studied [60] Glucocorticoids have been prescribed using different routes of administration and posology, in the clinic and in experimental models to develop more effective treatments of hearing loss [61,62]. Dexamethasone is a long-acting glucocorticoid with an anti-inflammatory potential about 25 times higher than that of short-acting products, such as hydrocortisone.…”

Section: Discussionmentioning

confidence: 99%

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Cervantes

Arana

Murillo-Cuesta

et al. 2019

JCM

View full text Add to dashboard Cite

Cisplatin is a chemotherapeutic agent that causes the irreversible death of auditory sensory cells, leading to hearing loss. Local administration of cytoprotective drugs is a potentially better option co-therapy for cisplatin, but there are strong limitations due to the difficulty of accessing the inner ear. The use of nanocarriers for the efficient delivery of drugs to auditory cells is a novel approach for this problem. Solid lipid nanoparticles (SLNs) are biodegradable and biocompatible nanocarriers with low solubility in aqueous media. We show here that stearic acid-based SLNs have the adequate particle size, polydispersity index and ζ-potential, to be considered optimal nanocarriers for drug delivery. Stearic acid-based SLNs were loaded with the fluorescent probe rhodamine to show that they are efficiently incorporated by auditory HEI-OC1 (House Ear Institute-Organ of Corti 1) cells. SLNs were not ototoxic over a wide dose range. Glucocorticoids are used to decrease cisplatin-induced ototoxicity. Therefore, to test SLNs’ drug delivery efficiency, dexamethasone and hydrocortisone were tested either alone or loaded into SLNs and tested in a cisplatin-induced ototoxicity in vitro assay. Our results indicate that the encapsulation in SLNs increases the protective effect of low doses of hydrocortisone and lengthens the survival of HEI-OC1 cells treated with cisplatin.

show abstract

Section: Discussionmentioning

confidence: 99%

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Cervantes

Arana

Murillo-Cuesta

et al. 2019

JCM

View full text Add to dashboard Cite

show abstract

“…Mean apoptotic cells in tumor tissue were identified as 2.2% (2-8) in the control group; 30% in the CDDP group; 5.43% (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15) in the MSC group; and 28.57% in the CDDP+MSC group. Statistical analysis identified more apoptosis in the CDDP and CDDP+MSC groups .…”

Section: Apoptosis Analysis With Tunel On Paraffin Sectionsmentioning

confidence: 99%

Evaluation of the Effect of Mesenchymal Stem Cells on Chemotherapy Response for Neuroblastoma Treatment in an Experimental Animal Model

Aktaş

Olgun

Eskicioğlu

et al. 2020

Preprint

View full text Add to dashboard Cite

High-dose cisplatin (CDDP) causes dose-limiting side effects in neuroblastoma (NB) treatment. Mesenchymal stem cells (MSC) are a current research area in cellular treatments due to multipotential characteristics. The aim of this study is to assess the interaction of MSC with CDDP in an athymic nude mouse NB model. Athymic male nude mice (n=28) were injected subcutaneously with C1300 NB cell line. After tumor growth to 1 cm diameter in 7-10 days, mice were randomly assigned to one of 4 experimental groups of control, CDDP treatment, MSC treatment and CDDP+MSC treatment with 7 mice in each group. Animals had basal auditory tests performed and had physiological serum or CDDP (20 mg/kg) injected into the peritoneum and were intravenously injected with 1×105 MSC once. Seven days later, hearing tests were performed again and the animals were sacrificed. Tumor tissue was assessed in terms of necrosis, apoptosis and viability. Apoptosis was evaluated with annexin V+PI flow cytometry analysis and TUNEL. Additionally, the MSC rate within the tumor was assessed with flow cytometry for triple CD34+ CD44+ and CD117-expression. Additionally, liver, kidney, brain and cochlear tissue were analyzed with light microscopy in terms of systemic side effect profile. Expression of the cochlear cell proteins of calretinin, math-1 and myosin2A were immunohistochemically assessed in ear sections. Statistical analysis used the nonparametric Kruskal Wallis and Mann Whitney U tests with p<0.05 significance. Tumor tissues were found to have statistically significantly higher levels of necrosis in the CDDP group and CDDP+MSC group compared to the control and MSC groups (p=0.001, p=0.006). The CDDP+MSC group had lower tumor necrosis rates than the CDDP group but this was not observed to have statistical significance (p=0.05). MSC did not change the tumor dimensions in the CDDP group (p=0.557). The groups administered MSC had higher triple CD34+ CD44+ and CD117- expression within tumor tissue compared to the control and CDDP groups. In the inner ear, the expression of cochlear cell proteins calretinin, math-1 and myosin2A were identified to be highest in the groups administered MSC. Auditory tests observed that the 15-decibel loss at 12, 16, 20 and 32 kHz frequencies in both ears with CDDP was resolved with MSC administration. With this study, IV administration of MSC treatment was observed to prevent the hearing loss caused by CDDP without disrupting the antitumor effect of CDDP. Systemic MSC may be assessed for clinical use to reduce the side effects of CDDP.

show abstract

“…Together, these data suggest that ROS generated, in part, through the activation of NADPH oxidase plays an essential role in cisplatin ototoxicity (Kim et al, ). Intra‐tympanic dexamethasone (DXM) has demonstrated protective effects against cisplatin‐induced hearing loss in a few animal studies and one clinical trial (Dinh et al, ). However, levels of protection with intra‐tympanic DXM vary significantly between studies.…”

Section: Nadph‐oxidase (Nox)mentioning

confidence: 99%

“…However, levels of protection with intra‐tympanic DXM vary significantly between studies. DXM causes reduction in oxidative stress and NOX‐3 production and decreased levels of apoptotic cell death (Dinh et al, ). Targeting the cochlear adenosine A1 receptor (A1AR) by trans‐tympanic injections of the agonist R‐phenylisopropyladenosine (R‐PIA) has been shown to reduce cisplatin‐induced inflammation and apoptosis in the rat cochlea and preserved hearing (Kaur et al, ).…”

Section: Nadph‐oxidase (Nox)mentioning

confidence: 99%

Signaling in the Auditory System: Implications in Hair Cell Regeneration and Hearing Function

Mittal

Debs

Nguyen

et al. 2017

Journal Cellular Physiology

Self Cite

View full text Add to dashboard Cite

Ear is a sensitive organ involved in hearing and balance function. The complex signaling network in the auditory system plays a crucial role in maintaining normal physiological function of the ear. The inner ear comprises a variety of host signaling pathways working in synergy to deliver clear sensory messages. Any disruption, as minor as it can be, has the potential to affect this finely tuned system with temporary or permanent sequelae including vestibular deficits and hearing loss. Mutations linked to auditory symptoms, whether inherited or acquired, are being actively researched for ways to reverse, silence, or suppress them. In this article, we discuss recent advancements in understanding the pathways involved in auditory system signaling, from hair cell development through transmission to cortical centers. Our review discusses Notch and Wnt signaling, cell to cell communication through connexin and pannexin channels, and the detrimental effects of reactive oxygen species on the auditory system. There has been an increased interest in the auditory community to explore the signaling system in the ear for hair cell regeneration. Understanding signaling pathways in the auditory system will pave the way for the novel avenues to regenerate sensory hair cells and restore hearing function. J. Cell. Physiol. 232: 2710-2721, 2017. © 2016 Wiley Periodicals, Inc.

show abstract

Dexamethasone Protects Against Apoptotic Cell Death of Cisplatin-exposed Auditory Hair Cells In Vitro

Abstract: DXM protects against cisplatin-induced loss of OHCs in the basal turn of rat OC explants as demonstrated by reductions in oxidative stress and NOX-3 production and decreased levels of apoptotic cell death.

Cited by 17 publications

References 12 publications

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Solid Lipid Nanoparticles Loaded with Glucocorticoids Protect Auditory Cells from Cisplatin-Induced Ototoxicity

Evaluation of the Effect of Mesenchymal Stem Cells on Chemotherapy Response for Neuroblastoma Treatment in an Experimental Animal Model

Signaling in the Auditory System: Implications in Hair Cell Regeneration and Hearing Function

Contact Info

Product

Resources

About