Purpose Cisplatin is a widely used and effective chemotherapeutic agent for most solid malignant tumors. However, cisplatin-induced ototoxicity is a common adverse effect that limits the therapeutic efficacy of tumors in the clinic. To date, the specific mechanism of ototoxicity has not been fully elucidated, and the management of cisplatin-induced ototoxicity is also an urgent challenge. Recently, some authors believed that miR34a and mitophagy played a role in age-related and drug-induced hearing loss. Our study aimed to explore the involvement of miR-34a/DRP-1-mediated mitophagy in cisplatin-induced ototoxicity. Methods In this study, C57BL/6 mice and HEI-OC1 cells were treated with cisplatin. MiR-34a and DRP-1 levels were analyzed by qRT‒PCR and western blotting, and mitochondrial function was assessed via oxidative stress, JC-1 and ATP content. Subsequently, we detected DRP-1 levels and observed mitochondrial function by modulating miR-34a expression in HEI-OC1 cells to determine the effect of miR-34a on DRP-1-mediated mitophagy. Results MiR-34a expression increased and DRP-1 levels decreased in C57BL/6 mice and HEI-OC1 cells treated with cisplatin, and mitochondrial dysfunction was involved in this process. Furthermore, the miR-34a mimic decreased DRP-1 expression, enhanced cisplatin-induced ototoxicity and aggravated mitochondrial dysfunction. We further verified that the miR-34a inhibitor increased DRP-1 expression, partially protected against cisplatin-induced ototoxicity and improved mitochondrial function. Conclusion MiR-34a/DRP-1-mediated mitophagy was related to cisplatin-induced ototoxicity and might be a novel target for investigating the treatment and protection of cisplatin-induced ototoxicity.

Background: Chronic suppurative otitis media (CSOM) is a common otolaryngology disease, and cholesteatoma is the most aggressive type of CSOM. CSOM with and without cholesteatoma both result in a certain level of sensorineural damage, which can be categorized as air conduction (AC), bone conduction (BC), or air-bone gap (ABG), and AC, BC, and ABG are affected by many factors. Further analyses and comparisons of factors affecting sensorineural damage in CSOM with and without cholesteatoma were conducted in this study.Methods: A comparative study was conducted of 79 patients with CSOM (39 with cholesteatoma and 40 without cholesteatoma) whose diagnoses were mainly based on chronic middle ear infections and hearing loss (HL), typical computed tomography (CT) and surgical findings. Audiological evaluation included AC, BC and ABG, and sensorineural damage was defined as mixed and sensorineural HL (SNHL). Results:In relation to the types of HL, there were no significant differences between both groups. The CSOM with cholesteatoma group had significantly greater AC (P=0.000) and a significantly greater ABG (P>0.05) than the CSOM without cholesteatoma group, but BC did not differ significantly between both groups (P>0.05). The average AC-middle frequency (MF), AC-high frequency (HF), ABG-MF and ABG-HF of CSOM without cholesteatoma were smaller than these of CSOM with cholesteatoma (P<0.05). The degree of HL differed significantly between both groups (P=0.000). The CSOM with cholesteatoma group showed a higher level of HL than the CSOM without cholesteatoma group. The presence of cholesteatoma was presented a protective factor associated with sensorineural damage (P<0.05), while higher degrees of hearing and aging were risk factors (P<0.05), respectively.Conclusions: Our direct comparisons showed that HL progressed more rapidly in the CSOM with cholesteatoma group, which had higher frequencies in relation to AC, the ABG, and severity. However, in relation to BC, there were no significant differences between both groups, which was in line with the similar proportions of the types of HL in both groups. The logistic regression showed that the presence of cholesteatoma was a protective factor, and the degree of hearing and aging were risk factors associated with sensorineural damage.

No abstract