otolaryngology-2019-posters-abstracts

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Otolaryngology 2019

Otolaryngology Online Journal | ISSN: 2250-0359 | Volume 9

July 18-19, 2019 | Valencia, Spain

OF EXCELLENCE

IN INTERNATIONAL

MEETINGS

YEARS

OTOLARYNGOLOGY: ENT SURGERY

Global Summit on

Otolaryngology Online Journal 2019, Volume 9

INHIBITION OF NFAT IN COMBINATIONWITH ANTIOXIDANTS PROVIDES AUDITORY

HAIR CELL PROTECTION FROM AMINOGLYCOSIDE TOXICITY

Marijana Sekulic, Krystsina Kucharava, Daniel Bodmer

and

Vesna Petkovic

University Hospital Basel, Switzerland

minoglycosides generate free radicals within the inner ear, resulting in permanent damage to sensory cells and

neurons, followed by hearing loss. Decreasing aminoglycoside-induced reactive oxygen species (ROS) produc-

tion was shown to be beneficial. Based on author’s previous study, preventing nuclear factor of activated T cells

(NFAT) nuclear accumulation preserves auditory hair cells from gentamicin toxicity. They addressed hair cell protec-

tion from two angles by using NFAT inhibitor 11R-VIVIT and one of the well-described antioxidants L-carnitine (LCAR)

or N-acetylcysteine (NAC). Organs of Corti (OCs) from 5-day old mice were exposed to gentamicin +/- 11R-VIVIT,

NAC or LCAR

in vitro

, followed by phalloidin based detection and counting of hair cells. Combined treatment with

11R-VIVIT and LCAR in the presence of gentamicin resulted in higher protection compared to single component

culture treatment. 11R-VIVIT combined with NAC provided practically full protection (>98%) of the hair cells com-

pared to single component treatment in the presence of gentamicin. Relative gene expression determined by qPCR

revealed decrease in Casp9 after exposure to 11R-VIVIT and increase Hmox1 after exposure to NAC, compared to

gentamicin treated OC cultures. In a caspase assay, combination of 11R-VIVIT and LCAR when compared to single

component treatments was shown to be less effective in decreasing apoptotic signals than the 11R-VIVIT combined

with NAC. Similar results were observed on heme oxygenase-1 western blot signals, where NAC combination showed

to be more effective than LCAR. Selective NFAT inhibition by 11R-VIVIT appears to be a good strategy in preventing

hair cell damage caused by gentamicin. L-carnitine and N-acetylcysteine with their ROS reducing properties could

contribute to the observed synergistic effectiveness with 11R-VIVIT through decrease of ROS induced NFAT translo-

cation. Our data suggest that combined approach of NFAT inhibition together with the presence of antioxidant like

N-acetylcysteine could be promising in the treatment and/or prevention of hearing loss.