Streptomycin generates oxidative stress in melanin-producing cells: In vitro study with EPR spectroscopy evidence

Abstract

Streptomycin (STR) is an aminoglycoside antibiotic with a broad-spectrum of activity and ototoxic potential. The mechanism of STR-induced inner ear damage has not been fully elucidated. It was previously found that STR binds to melanin, which may result in the accumulation of the drug in melanin-containing tissues. Melanin pigment is present in various parts of the inner ear, including the cochlea and vestibular organ.The present study aimed to assess if streptomycin generates oxidative stress and affects melanogenesis in normal human melanocytes. Moreover the variation of free radical concentration in STR-treated melanocytes was examined by electron paramagnetic resonance spectroscopy (EPR). We found that STR decreases cell metabolic activity and reduces melanin content. The observed changes in the activity of antioxidant enzymes activity in HEMn-DPs treated with streptomycin may suggest that the drug affects redox homeostasis in melanocytes. In this work EPR study expanded knowledge about free radicals in interactions of STR and melanin in melanocytes. The results may help elucidate the mechanisms of STR toxicity on pigment cells, including melanin-producing cells in the inner ear. This is important because understanding the mechanism of STR-induced ototoxicity would be helpful in developing new therapeutic strategies to protect patients' hearing.