Impact of kanamycin on melanogenesis and antioxidant enzymes activity in melanocytes--an in vitro study
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Published on: March 6, 2019
Dorota Wrześniok1, Michał Otręba, Artur Beberok
1Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Medical University of Silesia, Jagiellońska 4, PL 41-200, Sosnowiec, Poland.
Abstract:
Aminoglycosides, broad spectrum aminoglycoside antibiotics, are used in various infections therapy due to their good antimicrobial characteristics. However, their adverse effects such as nephrotoxicity and auditory ototoxicity, as well as some toxic effects directed to pigmented tissues, complicate the use of these agents. This study was undertaken to investigate the effect of aminoglycoside antibiotic-kanamycin on viability, melanogenesis and antioxidant enzymes activity in cultured human normal melanocytes (HEMa-LP). It has been demonstrated that kanamycin induces concentration-dependent loss in melanocytes viability. The value of EC50 was found to be ~6.0 mM. Kanamycin suppressed melanin biosynthesis: antibiotic was shown to inhibit cellular tyrosinase activity and to reduce melanin content in normal human melanocytes. Significant changes in the cellular antioxidant enzymes: SOD, CAT and GPx were stated in melanocytes exposed to kanamycin. Moreover, it was observed that kanamycin caused depletion of antioxidant defense sytem. It is concluded that the inhibitory effect of kanamycin on melanogenesis and not sufficient antioxidant defense mechanism in melanocytes in vitro may explain the potential mechanisms of undesirable side effects of this drug directed to pigmented tissues in vivo.
Insights
Kanamycin, an aminoglycoside antibiotic, harms human melanocyte viability and melanin production. This study suggests kanamycin
Area of Science:
- Pharmacology
- Toxicology
- Dermatology
Background:
- Aminoglycosides are broad-spectrum antibiotics effective against various infections.
- However, aminoglycosides can cause adverse effects like nephrotoxicity, ototoxicity, and toxicity to pigmented tissues.
- Kanamycin is a commonly used aminoglycoside antibiotic.
Purpose of the Study:
- To investigate the effects of kanamycin on human melanocyte viability, melanogenesis, and antioxidant enzyme activity.
- To explore the potential mechanisms behind kanamycin's toxicity to pigmented tissues.
Main Methods:
- Cultured human normal melanocytes (HEMa-LP) were treated with varying concentrations of kanamycin.
- Cell viability was assessed using EC50 values.
- Melanogenesis was evaluated by measuring tyrosinase activity and melanin content.
- Activity of antioxidant enzymes (SOD, CAT, GPx) was analyzed.
Main Results:
- Kanamycin induced a concentration-dependent decrease in melanocyte viability, with an EC50 of approximately 6.0 mM.
- Kanamycin suppressed melanin biosynthesis by inhibiting tyrosinase activity and reducing melanin content.
- Significant alterations in SOD, CAT, and GPx activity were observed, indicating depletion of the antioxidant defense system.
Conclusions:
- Kanamycin's inhibitory effect on melanogenesis and its detrimental impact on the antioxidant defense system in melanocytes may contribute to its observed toxicity in pigmented tissues.
- These findings provide insights into the mechanisms underlying aminoglycoside-induced side effects on pigmented tissues.
