Resveratrol Attenuates CoCl(2)-Induced Cochlear Hair Cell Damage through Upregulation of Sirtuin1 and NF-κB Deacetylation

The goals of this study were to investigate the effects of hypoxia on cochlear hair cell damage, and to explore the role of sirtuin1 in hypoxia-induced hair cell damage. Cochlear organotypic cultures from postnatal day 4 rats were used in this study. Hypoxia was induced by treating cochlear explants with CoCl(2). Cochlear cultures were treated with CoCl(2) alone or in combination with the sirtuin1 activator resveratrol and the sirtuin1 inhibitor sirtinol. Hair cell damage was identified by phalloidin staining and imaged using scanning electron microscopy. RT-PCR and Western blot analyses were used to detect the expression of sirtuin1 and acetylated nuclear factor-κB (NF-κB). Low concentrations of CoCl(2) (100–200 μM) did not cause an obvious change in the number and morphology of hair cells, whereas higher concentrations of CoCl(2) (300–400 μM) induced swelling of hair cells, accompanied by cell loss. Increased sirtuin1 expression was induced by CoCl(2) at 100 to 200 μM, but not at 400 μM. NF-κB acetylation was significantly increased in explants treated with 400 μM CoCl(2). Pretreatment with resveratrol prevented CoCl(2)-induced hair cell loss and acetylation of NF-κB. The protective effect of resveratrol was significantly reduced by sirtinol. CoCl(2) induces hair cell damage in organotypic cochleae cultures. Resveratrol attenuates CoCl(2)-induced cochlear hair cell damage possibly via activation of sirtuin1, which deacetylates NF-κB.