Murine Hearing ABR/DPOAE Assessments in CMV-Infected Mouse Pups Receiving Peritoneal Antivirals of GCV, Quercetin+P188, or a Combination. Controls Include Infected and Untreated and Non-Infected and Treated. Second Dataset of Antiviral Assay in a Murine Stria Vascularis (SV) Monolayer Cell Culture

Creators

David Britt, Utah State UniversityFollow
Albert Park, University of UtahFollow

Description

Ganciclovir (GCV) has been shown to be an effective antiviral for the treatment of congenital cytomegalovirus (cCMV) induced sensorineural hearing loss. However, dose-dependent adverse effects (e.g. neutropenia) require strict, burdensome monitoring, limiting GCV use in some patients. Quercetin is a flavonoid with antioxidant properties that has demonstrated antiviral therapy against CMV. Although more benign than GCV, quercetin has limited therapeutic value due to its poor solubility. We previously reported that GCV improves hearing thresholds in a murine model of cCMV. We also noted that solubilizing quercetin with poloxamer 188 (P188) and combining with GCV therapy amplified CMV inhibition in murine stria vascularis (SV) endothelial cell cultures. We hypothesized that combination therapy with a lower dose of GCV and a soluble Quercetin-P188 solution (GCV+QP188) would improve hearing outcomes in a murine CMV model. BALB/c mice were infected with 200 plaque-forming units of murine CMV via intracerebral injection on postnatal day 3 (p3). Quercetin was solubilized in saline using P188 (QP188). Treatment groups received either 1 mg/kg GCV, 220 mg/kg of QP188, a combination therapy of GCV+QP188, or 220 mg/kg of P188 delivery vehicle BID at 12-hour intervals via intraperitoneal injection. All treatment groups were treated for 14 days starting at p3. Uninfected controls were treated with the combined regimen and P188 delivery vehicle. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing at 4, 6, and 8 weeks of age. Temporal bones from separate CMV-infected were harvested at p10, and viral load was determined by quantitative polymerase chain reaction. CMV-infected mice receiving combination therapy GCV+QP188 demonstrated significantly lower ABR (P

Author ORCID Identifier

David Britt https://orcid.org/0000-0002-9753-6404

Albert Park https://orcid.org/0000-0001-9089-3014

Document Type

Dataset

DCMI Type

Dataset

File Format

.xlsx, .R, .csv

Publication Date

4-12-2023

Funder

USU Research Catalyst Program

Publisher

Utah State University

Methodology

Cell culture antiviral activity based on relative fluorescence unite (RFU) measurements from GFP expression in infected cells. FIC calculated based on RFUs of antiviral combinations in GFP-mCMV infected stria vascularis cells. Mouse hearing testing was performed beginning at 4 weeks of age to ensure maturity of the murine auditory system. Auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing were performed at 4, 6, and 8 weeks of age. ABR and DPOAE thresholds were assigned via visual inspection. Both ABR and DPOAE thresholds were tested over a sound pressure level range (dB SPL) of 10 to 80 dB across octaves of 8, 16, and 32 kHz. If there was no ABR or DPOAE response at the highest stimulus of 80 dB SPL, threshold was assigned the maximum value of 80 dB SPL.

Referenced by

Suarez, D. et al., "Otoprotective and Anti-cytomegalovirus Activity of Subtherapeutic Doses of Ganciclovir and Poloxamer 188 Delivered Quercetin", Current Research in Neurobiology, 2023 (under review)

Start Date

7-2021

End Date

9-2022

Language

eng

Code Lists

see README

Disciplines

Biomedical Engineering and Bioengineering

License

This work is licensed under a Creative Commons Attribution 4.0 License.

Identifier

https://doi.org/10.26078/r56w-y917

Recommended Citation

Britt, D., & Park, A. (2023). Murine Hearing ABR/DPOAE Assessments in CMV-Infected Mouse Pups Receiving Peritoneal Antivirals of GCV, Quercetin+P188, or a Combination. Controls Include Infected and Untreated and Non-Infected and Treated. Second Dataset of Antiviral Assay in a Murine Stria Vascularis (SV) Monolayer Cell Culture [Data set]. Utah State University. https://doi.org/10.26078/R56W-Y917

Checksum

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