A Comparative Study on the Interaction of an Ototoxic and an Otoprotective with the Megalin Receptor Associated with Hearing Loss

An aminoglycoside antibiotic is used to treat different pulmonary illnesses. These drugs save the lives of millions of people around the world, but they also could cause ototoxicity. Kanamycin is an aminoglycoside antibiotic that causes loss or damage of Hair Cell receptors in the inner ear, resulting in hearing loss. The megalin is an endocytic receptor for aminoglycosides in the cochlea. On the other hand, different studies use flutamide to protect the HCs from kanamycin. Androgen receptor inhibition protects against cochlear injuries in kanamycin-induced hearing loss. This work determined the stability of megalin-kanamycin and megalin-flutamide by calculating the binding energy (ΔGb). Our results showed that the megaline-kanamycin interaction was more favorable (with a stronger binding affinity); by contrast, megalin-flutamide was less favorable. These results characterize the driving forces responsible for binding kanamycin to megalin, allowing kanamycin to be internalized by megalin-mediated endocytosis, causing ototoxicity. Our results suggest flutamide does not undergo endocytosis and does not contribute to hearing loss. Currently, we are carrying out molecular docking studies considering megalin-ototoxic receptors to bind flutamide to understand the signaling pathway of aminoglycoside-induced ototoxicity.