The Effects of Steroids on Survival of Mouse and Human Tympanic Membrane Fibroblasts

Abstract

Objective Tympanic membrane (TM) fibroblast cytotoxicity of quinolone ear drops is enhanced by dexamethasone and fluocinolone. Hydrocortisone has not been evaluated. We aimed to assess the effects of these 3 steroids on mouse and human TM fibroblast survival. Study Design In vitro. Setting Academic laboratory. Subjects and Methods Mouse and human TM fibroblasts were exposed to hydrocortisone, dexamethasone, or fluocinolone at concentrations in commercial ear drops (1%, 0.1%, or 0.025%, respectively) and at steroid potency equivalents (1%, 0.033%, or 0.0033%, respectively), or dilute ethanol (control), twice within 24 hours or 4 times within 48 hours for 2 hours each time. Cells were observed with phase-contrast microscopy until the cytotoxicity assay was performed. Results Mouse and human TM fibroblasts treated with any of the steroids had lower survival after 24 and 48 hours compared to control (all P < .0001). After 24 hours, viability of mouse fibroblasts treated with the steroids was not different ( P > .05), while treatment with hydrocortisone decreased human TM fibroblast viability ( P < .0001). After 48 hours, at concentrations found in ear drops and at equivalent steroid potency, dexamethasone and fluocinolone had similar survival in mouse and human fibroblasts (all P > .05), but hydrocortisone had lower survival in both mouse ( P = .02 and P < .0001) and human ( P < .0001) fibroblasts. Phase-contrast images mirrored the cytotoxicity findings. Conclusion Steroids found in commercial ear drops reduce survival of mouse and human TM fibroblasts. Hydrocortisone appears to be more cytotoxic than the more potent steroids, dexamethasone and fluocinolone. These findings should be considered when assessing clinical outcomes of ototopical preparations.

Self-Assembly Study of Block Copolypeptoids in Response to pH and Temperature Stimulation

“…In this study, polypeptoid solutions were prepared at various concentrations (0.125, 0.25, 0.5, 1, and 2 mg/mL) in a complete culture medium ( Figure 8 ). Generally speaking, a sample is considered non-toxic to cells (with no cytotoxicity) when the relative cell viability is above 75% [ 38 ]. All the polypeptoid samples prepared in this study demonstrated relative cell viability above 75% for concentrations up to 2 mg/mL, indicating their non-toxicity towards cells.…”

Tympanoplasty Healing Outcomes With Use of Postoperative Otic Quinolones

“…As quinolone ear drops have only recently been shown to impact TM integrity (16)(17)(18)(19), we paid particular attention to the impact of the ear drops administered postoperatively. Corticosteroids have been known to have an inhibitory effect on TM healing for 30 years (27,28) The mechanisms responsible for the adverse effects of quinolones and steroids are complex and not fully understood (29)(30)(31)(32). However, we routinely initiate the use of these agents on the first postoperative day and continue these for a month, thereby exposing the canal and TM to relatively high concentrations during the early phase of healing.…”

The Influence of Ciprofloxacin–Dexamethasone Ear Drops on Perforation Closure Rates After Endoscopic Tympanoplasty

“…In 2007, an experimental study using a rat model concluded that ciprofloxacin-dexamethasone delayed healing of tympanic membrane perforations (4). A more recent paper has demonstrated that steroid preparations in commercial ear drops reduce survival of human tympanic membrane fibroblasts (5).…”