Cisplatin is a first-line chemotherapeutic agent in the treatment of malignant tumors with remarkable clinical effects and low cost. However, the ototoxicity and neurotoxicity of cisplatin greatly limit its clinical application. This article reviews the possible pathways and molecular mechanisms of cisplatin trafficking from peripheral blood into the inner ear, the toxic response of cisplatin to inner ear cells, as well as the cascade reactions leading to cell death. Moreover, this article highlights the latest research progress in cisplatin resistance mechanism and cisplatin ototoxicity. Two effective protective mechanisms, anti-apoptosis and mitophagy activation, and their interaction in the inner ear are discussed. Additionally, the current clinical preventive measures and novel therapeutic agents for cisplatin ototoxicity are described. Finally, this article also forecasts the prospect of possible drug targets for mitigating cisplatin-induced ototoxicity. These include the use of antioxidants, inhibitors of transporter proteins, inhibitors of cellular pathways, combination drug delivery methods, and other mechanisms that have shown promise in preclinical studies. Further research is needed to evaluate the efficacy and safety of these approaches.

Myelin undergoes various changes after nerve injury, and c‐Jun has a close relationship with Schwann cells (SCs). However, it remains unclear whether c‐Jun can be involved in nerve repair by regulating ferroptosis. To explore this, we first set up a facial nerve injury model and detected the changes of ferroptosis‐related proteins and c‐Jun by immunofluorescence and Western blot. Then, we cultured RSC 96 and pSCs, and studied the potential regulatory relationships by a combination of experimental methods such as CCK‐8, ELISA, immunofluorescence, qRT‐PCR, Western blot and viral transfection. Finally, we corroborated the role of c‐Jun through animal experiments. Our experiments revealed that ferroptosis occurs after facial nerve injury. Erastin decreased GPX4, c‐Jun proteins and GSH content, while PTGS2, NRF2, HO‐1 proteins, MDA, Fe²⁺ and ROS contents increased. This effect was inhibited after c‐Jun overexpression but was reversed after the addition of c‐Jun siRNA. Besides, we proved in vivo that c‐Jun could inhibit ferroptosis and promote the recovery of facial nerve function. In conclusion, our study identified the relationship between c‐Jun and ferroptosis during peripheral nerve injury repair, which provides new ideas for studying peripheral nerve injury and repair.

Background: Meniere’s disease (MD) is a complex and multifactorial inner ear disease. The etiology of MD is unclear. Significant progress had been made in diagnosis and treatment. Complete cure for this disease is still impossible. Objectives: This review covers the updated research results in MD in the past decades. Material and methods: Recent publications were critically reviewed. Results: The relationship between Endolymphatic hydrops and Meniere symptoms requires further study. Direct visualization of EH is achieved by special sequences of inner ear MRI. Appearance of EH could be observed in MD patients both in symptomatic and asymptomatic ears. Visualization of EH in vivo might make a great substantial improvement in diagnose of MD. The first goal of the management of MD is to reduce the attack frequency. Several safe and effective medical and surgical therapies are practiced to help patients to control vertigo and preserve hearing. Conclusions and significance: There has been no major breakthrough in the pathogenesis research of MD in recent years. Visualization of EH in vivo might make a great substantial improvement in diagnose of MD. Clinicians still have few effective ways to alleviate the progress of the disease.

Hereditary deafness is one of the most common human birth defects. GJB2 gene mutation is the most genetic etiology. Gap junction protein 26 (connexin26, Cx26) encoded by the GJB2 gene, which is responsible for intercellular substance transfer and signal communication, plays a critical role in hearing acquisition and maintenance. The auditory character of different Connexin26 transgenic mice models can be classified into two types: profound congenital deafness and late-onset progressive hearing loss. Recent studies demonstrated that there are pathological changes including endocochlear potential reduction, active cochlear amplification impairment, cochlear developmental disorders, and so on, in connexin26 deficiency mice. Here, this review summarizes three main hypotheses to explain pathological mechanisms of connexin26-related hearing loss: potassium recycling disruption, adenosine-triphosphate-calcium signaling propagation disruption, and energy supply dysfunction. Elucidating pathological mechanisms underlying connexin26-related hearing loss can help develop new protective and therapeutic strategies for this common deafness. It is worthy of further study on the detailed cellular and molecular upstream mechanisms to modify connexin (channel) function.

Resveratrol is a non-flavonoid polyphenol compound that exists in many plants, and is considered an antitoxin. This study explores the effects from the regulation of miR-455-5p by resveratrol on cisplatin-induced ototoxicity via the PTEN–PI3K–AKT signaling pathway. For this, House Ear Institute–Organ of Corti 1 (HEI-OC1) cells were transfected with miR-455-5p inhibitor and treated with cisplatin and resveratrol, then cell proliferation, apoptosis, and oxidative stress were evaluated. A mouse model of hearing loss was established, and these mice were treated with cisplatin, resveratrol, or cisplatin combined with resveratrol, by intraperitoneal injection. The auditory brainstem response (ABR) threshold was measured, and hair cells were examined using immunofluorescence staining. The expression levels of miR-455-5p, PTEN, and PI3K/Akt proteins were examined. The results from our in-vitro experiments indicate that resveratrol promoted viability and reduced apoptosis and oxidative stress in cisplatin-induced HEI-OC1 cells. Resveratrol upregulated miR-455-5p, downregulated PTEN, and activated the PI3K–Akt axis. These effects of resveratrol were reversed by knock-down of miR-455-5p. The results from our in-vivo experiments indicate that resveratrol protected hearing and inhibited the hair-cell injury caused by cisplatin ototoxicity. Resveratrol also upregulated miR-455-5p, downregulated PTEN, and activated the PTEN–PI3K–Akt axis in cochlear tissues from cisplatin-treated mice. These results indicate that resveratrol upregulates miR-455-5p to target PTEN and activate the PI3K–Akt signaling pathway to counteract cisplatin ototoxicity.

Mutations in the GJB2 gene that encodes connexin 26 (Cx26) are the predominant cause of prelingual hereditary deafness, and the most frequently encountered variants cause complete loss of protein function. To investigate how Cx26 deficiency induces deafness, we examined the levels of apoptosis and autophagy in Gjb2^loxP/loxP; ROSA26^CreER mice injected with tamoxifen on the day of birth. After weaning, these mice exhibited severe hearing impairment and reduced Cx26 expression in the cochlear duct. Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) positive cells were observed in apical, middle, and basal turns of Kölliker’s organ at postnatal (P) day 1 (P1), associated with increased expression levels of cleaved caspase 3, but decreased levels of autophagy-related proteins LC3-II, P62, and Beclin1. In Kölliker’s organ cells with decreased Cx26 expression, we also found significantly reduced levels of intracellular ATP and hampered Ca²⁺ responses evoked by extracellular ATP application. These results offer novel insight into the mechanisms that prevent hearing acquisition in mouse models of non-syndromic hearing impairment due to Cx26 loss of function.