PROTECTIVE EFFECTS IN VIVO OF DEXAMETHASONE AGAINST CISPLATIN-INDUCED TOXICITY

In mammals, inner hair cells have lost their regenerative abilities. Thus, when they are damaged, acoustic signal transduction from hair cells to the spiral ganglion is irreversibly compromised and profound sensorineural hearing loss occurs. Ototoxicity and inner hair cell damage are relevant side effects of cisplatin, a widely employed chemotherapeutic drug. The aim of this study is to evaluate the in vivo otoprotective effects of dexamethasone, an anti-inflammatory drug, administered before intraperitoneal treatment with cisplatin in Wistar rats. Dexamethasone and cisplatin treatment were tested either alone or in combination. Both cochleas and kidneys were explanted from each group after dexamethasone, cisplatin or dexamethasone-cisplatin treatments, and processed for histological analyses. The preliminary morphological analysis by haematoxylin-eosin staining on cochlea and kidney tissues showed some protective effects of dexamethasone against cisplatin toxicity. For each group, one cochlea per animal was processed for scanning electron microscopy (SEM) to visualize hair cell morphology in the organ of Corti. As expected, cisplatin treatment induced hair cell loss and marked disorganization of the stereocilia, while pre-treatment by dexamethasone before cisplatin administration significantly reduced the ototoxic effects: hair cell structure was mostly maintained. However, the treatment by dexamethasone alone had some morphological effects on stereocilia, which appeared shorter in comparison to untreated animals. Based on these results, preliminary immunofluorescence experiments were performed with myosin 7A, anti-glucocorticoid receptor antibodies and apoptotic markers (cytochrome c and p53). The overall results supported the protective effects of dexamethasone against cisplatin-induced ototoxicity.