Dual viscosity mixture vehicle for intratympanic steroid treatment modifies the ROS and inflammation related proteomes

Jin Woo Jung; Hui Li; Jung Hun Lee; Yu-Jung Hwang; Kisoon Dan; Moo Kyun Park; Dohyun Han; Myung-Whan Suh

doi:10.3389/fphar.2023.1081724

Dual viscosity mixture vehicle for intratympanic steroid treatment modifies the ROS and inflammation related proteomes

Front Pharmacol. 2023 Jan 19:14:1081724. doi: 10.3389/fphar.2023.1081724. eCollection 2023.

Authors

Jin Woo Jung¹, Hui Li², Jung Hun Lee¹, Yu-Jung Hwang², Kisoon Dan¹, Moo Kyun Park², Dohyun Han^{1

3}, Myung-Whan Suh²

Affiliations

¹ Proteomics Core Facility, Transdisciplinary Research and Collaboration, Biomedical Research Institute, Seoul National University Hospital, Seoul, South Korea.
² Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Hospital, Seoul, South Korea.
³ Transdisciplinary Department of Medicine and Advanced Technology, Seoul National University Hospital, Seoul, South Korea.

Abstract

Until recently, the most standard treatment for sensorineural or sudden hearing loss, which is caused by inner ear damage or deterioration, has been systemic oral steroid administration. In recent, intratympanic steroid injections such as dexamethasone have been used for the treatment of sudden hearing loss as well. It is injected into the tympanic cavity through its membrane and is expected to diffuse over the round window located between the tympanic cavity and the inner ear. However, in clinical situations, the delivery time of steroids to the inner ear is shorter than 24 h, which does not allow for a sufficient therapeutic effect. Therefore, we applied a previously invented dual viscosity mixture vehicle (DVV) for intratympanic dexamethasone to a guinea pig model, which could reduce the side effects of systemic steroid administration with sufficient dwelling time for the treatment of hearing loss, and we investigated the physiological changes with a global proteomic approach. In this study, we extracted perilymph in three different conditions from guinea pigs treated with dexamethasone-embedded DVV, dexamethasone mixed in saline, and control groups to compare proteomic changes using tandem mass spectrometry analysis. After liquid chromatography coupled tandem mass spectrometry (LC-MS/MS) analysis, we first identified 46 differentially expressed proteins (DEPs) that were statistically significant after one-way ANOVA multiple-sample test. We also performed pairwise comparisons among each group to identify DEPs closely related to the treatment response of dexamethasone-embedded DVV. Gene ontology enrichment analysis showed that these DEPs were mostly related to inflammation, immune, actin remodeling, and antioxidant-related processes. As a result, the proteome changes in the DVV-treated groups revealed that most upregulated proteins activate the cell proliferation process, and downregulated proteins inhibit apoptosis and inflammatory reactions. Moreover, the reactive oxygen process was also regulated by DEPs after DVV treatment.

Keywords: ROS; inflammatory response; intratympanic steroid; perilymph; proteomics.

Grants and funding

This work was supported by the Materials/Parts Technology Development Program (Development of industry process of a new hyaluronic acid, 200 Pa·s or more, of more than 20 times compared to the existing for sustained-release DDS, 1415178889, 20016715) funded By the Ministry of Trade, Industry and Energy (MOTIE, Korea).