Cisplatin-Induced Hair Cell Death Requires STAT1 and Is Attenuated by Epigallocatechin Gallate

• DOI: 10.1523/jneurosci.5842-08.2009
• Publication Date: 2009-03-25T17:58:01Z
• Authors: Nicole C. Schmitt; Edwin W Rubel; Neil M. Nathanson
• Keywords: Gallate

Cisplatin is a chemotherapy drug that frequently causes auditory impairment due to the death of mechanosensory hair cells. ototoxicity may result from oxidative stress, DNA damage, and inflammatory cytokines. The transcription factor STAT1, an important mediator cell death, can regulate all these processes in other types. We used cultured utricles mature Swiss Webster mice investigate role STAT1 cisplatin-induced death. show phosphorylation early event both cells support after exposure cisplatin. peaked 4 h cisplatin returned control levels by 8 exposure. inhibitor epigallocatechin gallate (EGCG) attenuated cisplatin-treated resulted concentration-dependent increases survival at 24 postexposure. Furthermore, we utricular STAT1-deficient are resistant toxicity. EGCG failed provide additional protection mice, further supporting hypothesis protective effects its inhibition STAT1. Treatment with IFN-γ, which also activation, induced wild-type but not mice. These results required for maximal mouse utricle suggest treatment be useful strategy prevention ototoxicity.