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Title of Journal: Cell Mol Life Sci

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Abbravation: Cellular and Molecular Life Sciences

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SP Birkhäuser Verlag Basel

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DOI

10.1007/s00392-013-0609-7

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ISSN

1420-9071

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siRNAmediated knockdown of NOX3 therapy for hea

Authors: Leonard P Rybak Debashree Mukherjea Sarvesh Jajoo Tejbeer Kaur Vickram Ramkumar
Publish Date: 2012/05/05
Volume: 69, Issue: 14, Pages: 2429-2434
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Abstract

Cisplatin is a widely used chemotherapeutic agent that causes significant hearing loss Previous studies have shown that cisplatin exposure is associated with increase in reactive oxygen species ROS in the cochlea The inner ear expresses a unique isoform of NADPH oxidase NOX3 This enzyme may be the primary source of ROS generation in the cochlea The knockdown of NOX3 by pretreatment with siRNA prevented cisplatin ototoxicity as demonstrated by preservation of hearing thresholds and inner ear sensory cells Transtympanic NOX3 siRNA reduced the expression of NOX3 and biomarkers of cochlear damage including transient receptor vanilloid 1 TRPV1 channel and kidney injury molecule1 KIM1 in cochlear tissues In addition siRNA against NOX3 reduced apoptosis as demonstrated by TUNEL staining and prevented the increased expression of Bax and abrogated the decrease in Bcl2 expression following cisplatin administration Transtympanic administration of siRNA directed against NOX3 may provide a useful method of attenuating cisplatin ototoxicity In this paper we review recent publications dealing with the role of NOX3 in ototoxicity and the effects of siRNA against cisplatininduced hearing loss

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