Protective effect of rosmarinic acid is through regulation of inflammatory cytokine in cadmium-induced ototoxicity.

Cadmium ( Cd(2+) ) is an environmental contaminant that causes a variety of adverse effects. Auditory cells are sensitive to cadmium, and the cochlea is more vulnerable to cadmium toxicity than the other parts of the auditory system. Rosmarinic acid (RA) exhibits a wide spectrum of biological activities, mainly antioxidant and anti-inflammatory activities. However, the regulatory effects of RA in the auditory system have not been elucidated. In this study, we investigated the protective effects of RA on Cd(2+) -induced ototoxicity in vitro and ex vivo. The findings showed that RA inhibited Cd(2+) -mediated cell toxicity, reactive oxygen species generation, interleukin (IL)-6 and IL-1β production, the translocation of the apoptosis inducing factor into the nucleus and activation of caspases-3 in an auditory cell line, HEI-OC1. In addition, RA prevented the destruction of hair cell arrays in the rat organ of Cortiprimary explants in the presence of Cd(2+) . These results are expected to improve our understanding of the pharmacological mechanism of RA, and help develop potential therapeutic strategies against ototoxicity.