Kanamycin induces free radicals formation in melanocytes: An important factor for aminoglycosides ototoxicity

Abstract

Ototoxicity is well‐documented but not fully understood undesirable side effect of aminoglycoside antibiotic, kanamycin. Kanamycin is capable of binding to melanin biopolymers—natural pigments of the skin, hair, and eyes. Melanin‐producing cells, melanocytes, are also present in the inner ear and are known to be necessary for normal hearing. It was considered that melanin content in the inner ear may influence aminoglycoside‐induced ototoxic effect. The impact of kanamycin on melanocytes homeostasis may thus play role in the antibiotic‐induced ototoxic effect. Previously, we demonstrated that kanamycin disturbs homeostasis in light‐pigmented melanocytes. To investigate if/how melanization contributes to this phenomenon, the study using in vitro model of dark‐pigmented melanocytes is required. Spectrophotometric measurements and electron paramagnetic resonance (EPR) spectroscopy analysis were performed. Kanamycin induced a concentration‐dependent loss in HEMn‐DP melanocytes viability. The value of IC 50 was estimated to be 5.0 mM. Modulation of the activity of analyzed antioxidant enzymes and increased production of free radicals as well as the decrease of the melanin content were observed. Our results confirmed that kanamycin generates oxidative stress in melanocytes. The increased level of free radicals caused by kanamycin may be responsible for the imbalance of antioxidant defense and the reduction of melanin content in melanocytes. The role of melanin in the mechanism of kanamycin‐induced hearing impairment was discussed and the obtained results were compared with the previously demonstrated data concerning light‐pigmented melanocytes.

Association of vitiligo with high‐frequency sensorineural hearing loss: a systematic review and meta‐analysis

“…[43][44][45] The amounts of melanin are most abundant at the cochlea base which is in charge of high-frequency hearing only. 46,47 Anti-melanocyte antibodies presenting in vitiligo can attack the inner ear melanocytes, resulting in decreased amounts of melanin and increased susceptibility to highfrequency sensorineural hearing loss, which is compatible with our findings.…”

“…Also, melanocytes regulate potassium channels involved in the endocochlear electrical potential that is important in signal transmission of auditory function 43–45 . The amounts of melanin are most abundant at the cochlea base which is in charge of high‐frequency hearing only 46,47 . Anti‐melanocyte antibodies presenting in vitiligo can attack the inner ear melanocytes, resulting in decreased amounts of melanin and increased susceptibility to high‐frequency sensorineural hearing loss, which is compatible with our findings.…”

Antioxidant Property and Bactericidal Activity of Linum usitatissimum Seed Essential Oil Nanoemulsion (LSEO-NE) on Staphylococcus aureus

“…Different types of antibiotics, such as kanamycin, have been introduced for the treatment of such infections (13). However, several undesirable side effects have been reported for kanamycin consumption, such as ototoxic effects (14). Thus, the search for a less toxic and safe compound seems to be required.…”

Cobalamin Deficiency: Effect on Homeostasis of Cultured Human Astrocytes

“…Intracellular activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were estimated using the spectrophotometric assay kits (Cayman) according to a previously described method [23]. The analyses were performed on cell lysates prepared from astrocytes at day 27 of the culture in medium with/without (OH)Cbl(c-lactam).…”