Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation

Paciello, Fabiola; Pisani, Anna; Rolesi, Rolando; Escarrat, Vincent; Galli, Jacopo; Paludetti, Gaetano; Grassi, Claudio; Troiani, Diana; Fetoni, Anna Rita

doi:10.3390/antiox10081188

Cited by 12 publications

(16 citation statements)

References 75 publications

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“…However, in most of the studies to date, the focus was on the protective effect of ALA rather than its rescue effect. Because oxidative damage is considered a cause of acute inner ear diseases such as ISSNHL and NIHL [ 29 , 32 ], studies in which antioxidants are used for hearing rescue are needed. Therefore, the present study was conducted, and results showed IT administration of ALA was safe and had a better hearing rescue effect with higher concentration of the drug in the cochlea com-pared with IP administration.…”

Section: Discussionmentioning

confidence: 99%

“…Various action mechanisms of the two drugs may explain the different expression levels of the inflammatory markers within the cochlea between the IT-ALA and IT-DEX groups. IL-1ß and NF-κB are inflammatory markers activated due to ROS stimulation induced by acoustic trauma [ 29 ]. In a previous study, a biphasic elevation of IL-1ß was reported after acute acoustic trauma: the first peak at 6 h and the second peak at 7 days after noise exposure [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, a biphasic elevation of IL-1ß was reported after acute acoustic trauma: the first peak at 6 h and the second peak at 7 days after noise exposure [ 33 ]. In another study, a significant increase in both IL-1ß and NF-κB expression was observed until seven days after acoustic trauma that was reduced by another antioxidant (Q-ter) and anti-inflammatory (IL-1 receptor antagonist, anakinra) treatment [ 29 ]. In the present study, IL-1ß and NF-κB expression were evaluated in the cochlea at one and three weeks after noise exposure to investigate the inflammatory response at one week and later.…”

Section: Discussionmentioning

confidence: 99%

“…Immunofluorescence assays were performed with two inflammatory markers associated with noise-induced cochlear inflammation and oto-protective mechanism of ALA: interleukin-1 beta (IL-1ß) and nuclear factor-kappa B (NF-κB) [ 27 , 28 , 29 ]. Animals were sacrificed at 1 week to investigate IL-1ß and NF-κB expression which was reportedly increased at this time point after acoustic trauma [ 29 ]. In addition, to investigate the long-term efficacy of IT-ALA after acoustic trauma, the expression of these inflammatory markers was evaluated 3 weeks after drug administration.…”

Section: Methodsmentioning

confidence: 99%

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Safety and Efficacy of Intratympanic Alpha-Lipoic Acid Injection in a Mouse Model of Noise-Induced Hearing Loss

Han

Kim

et al. 2022

Antioxidants

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Alpha-lipoic acid (ALA) is an antioxidant with oto-protective effects. In the present study, the safety and effectiveness of ALA therapy after noise-induced hearing loss was confirmed based on the administration method. The safety of intratympanic ALA (IT-ALA) was evaluated with oto-endoscopy and middle ear mucosa morphologic study. Perilymph ALA concentrations according to the administration routes were compared, and the efficacy of ALA was investigated through hearing tests and cochlear histological studies. The middle ear mucosa was swollen 1 week after IT-ALA but completely recovered within 3 weeks. ALA concentration in the perilymph was significantly higher in the IT-ALA group. Recovery of organ of Corti morphology and hearing levels were predominant in the IT-ALA group compared with the intraperitoneal injection group (IP-ALA) and showed similar rescue effects in the IT-dexamethasone group (IT-DEX). Interleukin-1 beta and nuclear factor-kappa B expression was significantly downregulated in the IT-ALA group. IT-ALA showed better cochlear recovery from acoustic trauma with higher inner ear penetration rate than IP-ALA. The rescue effect of IT-ALA after noise-induced hearing loss was similar to IT-DEX; however, the ALA and DEX mechanisms are different. IT-ALA appears to be another safe and effective treatment modality after acoustic trauma and comparable to IT-DEX.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Safety and Efficacy of Intratympanic Alpha-Lipoic Acid Injection in a Mouse Model of Noise-Induced Hearing Loss

Han

Kim

et al. 2022

Antioxidants

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“…When used with gentamicin in in vitro studies conducted by Sekulic-Jablanovic et al, pioglitazone demonstrated a protective cochlear effect against oxidative stress and prevented gentamicin toxicity [67,68]. As PPARs are involved in noise exposure cochlear damage [69], Paciello et al used pioglitazone in a biocompatible thermogel via transtympanic injection in rats with noise-induced hearing loss [70]. The authors documented a diminished ABR threshold shift and decreased hair cell loss in the middle-basal turn, but no considerable effect was noted in the apical cochlear turn.…”

Section: Pioglitazone (Antioxidant)mentioning

confidence: 99%

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review

et al. 2022

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Hearing loss is the most common neurosensory disorder, and with the constant increase in etiological factors, combined with early detection protocols, numbers will continue to rise. Cochlear implantation has become the gold standard for patients with severe hearing loss, and interest has shifted from implantation principles to the preservation of residual hearing following the procedure itself. As the audiological criteria for cochlear implant eligibility have expanded to include patients with good residual hearing, more attention is focused on complementary development of otoprotective agents, electrode design, and surgical approaches. The focus of this review is current aspects of preserving residual hearing through a summary of recent trends regarding surgical and pharmacological fundamentals. Subsequently, the assessment of new pharmacological options, novel bioactive molecules (neurotrophins, growth factors, etc.), nanoparticles, stem cells, and gene therapy are discussed.

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Interleukin 1β triggers synaptic and memory deficits in Herpes simplex virus type-1-infected mice by downregulating the expression of synaptic plasticity-related genes via the epigenetic MeCP2/HDAC4 complex

Puma

Colussi

Bandiera

et al. 2023

Cell. Mol. Life Sci.

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Extensive research provides evidence that neuroinflammation underlies numerous brain disorders. However, the molecular mechanisms by which inflammatory mediators determine synaptic and cognitive dysfunction occurring in neurodegenerative diseases (e.g., Alzheimer’s disease) are far from being fully understood. Here we investigated the role of interleukin 1β (IL-1β), and the molecular cascade downstream the activation of its receptor, to the synaptic dysfunction occurring in the mouse model of multiple Herpes simplex virus type-1 (HSV-1) reactivations within the brain. These mice are characterized by neuroinflammation and memory deficits associated with a progressive accumulation of neurodegenerative hallmarks (e.g., amyloid-β protein and tau hyperphosphorylation). Here we show that mice undergone two HSV-1 reactivations in the brain exhibited increased levels of IL-1β along with significant alterations of: (1) cognitive performances; (2) hippocampal long-term potentiation; (3) expression synaptic-related genes and pre- and post-synaptic proteins; (4) dendritic spine density and morphology. These effects correlated with activation of the epigenetic repressor MeCP2 that, in association with HDAC4, affected the expression of synaptic plasticity-related genes. Specifically, in response to HSV-1 infection, HDAC4 accumulated in the nucleus and promoted MeCP2 SUMOylation that is a post-translational modification critically affecting the repressive activity of MeCP2. The blockade of IL-1 receptors by the specific antagonist Anakinra prevented the MeCP2 increase and the consequent downregulation of gene expression along with rescuing structural and functional indices of neurodegeneration. Collectively, our findings provide novel mechanistic evidence on the role played by HSV-1-activated IL-1β signaling pathways in synaptic deficits leading to cognitive impairment.

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Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation

Cited by 12 publications

References 75 publications

Safety and Efficacy of Intratympanic Alpha-Lipoic Acid Injection in a Mouse Model of Noise-Induced Hearing Loss

Safety and Efficacy of Intratympanic Alpha-Lipoic Acid Injection in a Mouse Model of Noise-Induced Hearing Loss

Current Concepts and Future Trends in Increasing the Benefits of Cochlear Implantation: A Narrative Review

Interleukin 1β triggers synaptic and memory deficits in Herpes simplex virus type-1-infected mice by downregulating the expression of synaptic plasticity-related genes via the epigenetic MeCP2/HDAC4 complex

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