Protective effects of minocycline and MDL 28170 in gentamicin ototoxicity

Gentamicin side-effects on cochlear structures and function are well known, but not the detailed intracellular molecular mechanisms which lead to aminoglycoside induced ototoxicity. Hair cell death occurs by apoptosis, by the activation of enzymatic cascades known to be involved in the programmed cell death, or by the release of cytochrome-c from the damaged mitochondria. In this paper we have investigated the active role of minocycline, a second-generation tetracycline, and of MDL 28170, a selective calpain inhibitor, in the protection of hair cells from GM damage in in vitro organospecific cultures of the organ of Corti. We used cultures from neonatal (P3) rat cochlea, treated with different dosages of GM, alone, or with the two protector drugs. We have observed a dose-dependent OHC and IHC loss. The GM damage was reduced after treatment with both drugs. These results were also supported by the Disk Diffusion Susceptibility Test (Kirby-Bauer Method), in which we used drug treated organs of Corti. The data suggest that minocycline, previously reported to inhibit the release of cytochrome-c, and MDL 28170, prevent GM induced programmed cell death pathway in cochlear HC.