Forskolin protects against cisplatin-induced ototoxicity by inhibiting apoptosis and ROS production

Cisplatin is widely used in the treatment of various types of cancer. However, it could cause severe side effects such as ototoxicity, which greatly limit the clinical application of cisplatin. Forskolin (FSK) is a diterpene derived from the plant Coleus forskohlii, and has been proven an effective drug for cardiovascular disease, diabetes, and asthma because of its anti-oxidant and anti-inflammatory action. Here, we investigated the effects of FSK in cisplatin-induced ototoxicity, and we found that FSK could significantly protect against cisplatin-induced ototoxicity in both cell line and isolated mouse cochlear. Pretreatment of FSK attenuated cisplatin-induced hearing loss especially at high frequency regions. FSK inhibited the activation of mitochondrial apoptotic pathway as well as reactive oxygen species (ROS) production. Moreover, we identified PKA and MAPK signaling pathway which may be connected with the protective effect of FSK. Our study provided the first evidence that FSK may be used as a drug to weaken the ototoxicity induced by cisplatin.