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Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses

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Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses

dc.contributor.author	Bas, E	es_ES
dc.contributor.author	Van De Water, TR	es_ES
dc.contributor.author	Gupta, C	es_ES
dc.contributor.author	Dinh, J	es_ES
dc.contributor.author	Vu, L	es_ES
dc.contributor.author	Martínez-Soriano, F	es_ES
dc.contributor.author	Láinez Andrés, José Miguel	es_ES
dc.contributor.author	Marco, J	es_ES
dc.date.accessioned	2015-06-19T10:19:52Z
dc.date.available	2015-06-19T10:19:52Z
dc.date.issued	2012	es_ES
dc.identifier.citation	British Journal of Pharmacology Vol. 166 Issue 6: pp. 1888-1904	es_ES
dc.identifier.uri	http://hdl.handle.net/10550/44553
dc.description.abstract	BACKGROUND AND PURPOSEExposure to an ototoxic level of an aminoglycoside can result in hearing loss. In this we study investigated the otoprotective efficacy of dexamethasone (DXM), melatonin (MLT) and tacrolimus (TCR) in gentamicin (GM)-treated animals and cultures.EXPERIMENTAL APPROACHWistar rats were divided into controls (treated with saline); exposed to GM only (GM); and three GM-exposed groups treated with either DXM, MLT or TCR. Auditory function and cochlear surface preparations were studied. In vitro studies of oxidative stress, pro-inflammatory cytokine mRNA levels, the MAPK pathway and caspase-3 activation were performed in organ of Corti explants from 3-day-old rats.KEY RESULTSDXM, MLT and TCR decreased levels of reactive oxygen species in GM-exposed explants. The mRNA levels of TNF-α, IL-1β and TNF-receptor type 1 were significantly reduced in GM + DXM and GM + MLT groups. Phospho-p38 MAPK levels decreased in GM + MLT and GM + TCR groups, while JNK phosphorylation was reduced in GM + DXM and GM + MLT groups. Caspase-3 activation decreased in GM + DXM, GM + MLT and GM + TCR groups. These results were consistent with in vivo results. Local treatment of GM-exposed rat cochleae with either DXM, MLT or TCR preserved auditory function and prevented auditory hair cell loss.CONCLUSIONS AND IMPLICATIONSIn organ of Corti explants, GM increased oxidative stress and initiated an inflammatory response that led to the activation of MAPKs and apoptosis of hair cells. The three compounds tested demonstrated otoprotective properties that could be beneficial in the treatment of ototoxicity-induced hearing loss.	es_ES
dc.subject	laboratory rats	es_ES
dc.subject	DPOAEs	es_ES
dc.subject	ABRs	es_ES
dc.subject	ototoxicity	es_ES
dc.subject	gentamicin	es_ES
dc.subject	otoprotection	es_ES
dc.subject	dexamethasone	es_ES
dc.subject	melatonin	es_ES
dc.subject	tacrolimus	es_ES
dc.title	Efficacy of three drugs for protecting against gentamicin-induced hair cell and hearing losses	es_ES
dc.type	journal article	es_ES
dc.identifier.doi	10.1111/j.1476-5381.2012.01890.x	es_ES
dc.identifier.idgrec	084583	es_ES