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Published on: September 7, 2013
Gentamicin affects melanogenesis in normal human melanocytes
Dorota Wrześniok1, Artur Beberok, Michał Otręba
1Department of Pharmaceutical Chemistry, Medical University of Silesia in Katowice , Sosnowiec , Poland.
Background:
Aminoglycoside antibiotics, including gentamicin, despite their ability to induce adverse effects on pigmented tissues, remain valuable and sometimes indispensable for the treatment of various infections. It is known that gentamicin binds to melanin biopolymers, but the relation between this drug affinity to melanin and its toxicity is not well documented. The aim of this work was to examine the impact of gentamicin on viability and melanogenesis in HEMa-LP (light pigmented) and HEMn-DP (dark pigmented) normal human melanocytes.
Methodology/Principal Findings:
The effect of gentamicin on cell viability was determined by 4-[3-(4-iodophenyl)-2-(4-nitrophenyl)-2H-5-tetrazolio]-1,3-benzene disulfonate (WST-1) assay; melanin content and tyrosinase activity were measured spectrophotometrically. It has been demonstrated that gentamicin induces concentration-dependent loss in melanocytes viability. The application of antibiotic in concentration of 10 mM causes higher reduction in viability of the light pigmented melanocytes (by about 74%) when compared with the dark pigmented ones (by about 62%). The value of the concentration of a drug that produces loss in cell viability by 50% (EC50) for both cell lines was found to be ∼7.5 mM. It has been shown that gentamicin causes inhibition of tyrosinase activity and reduces melanin content in light pigmented melanocytes significantly more than in the dark pigmented cells.
Conclusion/Significance:
We have found that gentamicin modulates melanization process in melanocytes in vitro, what may explain the potential role of melanin biopolymer in the mechanisms of undesirable toxic effects of this drug in vivo, as a result of its accumulation in pigmented tissues. We have also stated that the melanogenesis process in light pigmented melanocytes is more sensitive to the inhibitory effect of gentamicin than in the dark pigmented cells.
Insights
Gentamicin antibiotic reduces melanocyte viability and melanin production. Light pigmented cells are more sensitive to gentamicin
Area of Science:
- Pharmacology
- Toxicology
- Dermatology
Background:
- Gentamicin, an aminoglycoside antibiotic, is crucial for treating infections but can cause adverse effects on pigmented tissues.
- The binding of gentamicin to melanin is known, yet its direct link to toxicity remains poorly understood.
- Investigating gentamicin's impact on melanocytes is essential for understanding its side effects in pigmented tissues.
Purpose of the Study:
- To examine the effect of gentamicin on the viability of normal human melanocytes.
- To assess gentamicin's impact on melanogenesis (melanin production) in normal human melanocytes.
- To compare these effects between light-pigmented (HEMa-LP) and dark-pigmented (HEMn-DP) melanocytes.
Main Methods:
- Cell viability was measured using the WST-1 assay.
- Melanin content was quantified spectrophotometrically.
- Tyrosinase activity, a key enzyme in melanin synthesis, was also measured spectrophotometrically.
Main Results:
- Gentamicin induced a concentration-dependent decrease in melanocyte viability.
- Light-pigmented melanocytes showed a greater reduction in viability (74%) compared to dark-pigmented cells (62%) at 10 mM.
- Gentamicin significantly inhibited tyrosinase activity and reduced melanin content more in light-pigmented melanocytes than in dark-pigmented ones.
Conclusions:
- Gentamicin modulates the melanization process in melanocytes.
- Melanin biopolymer may play a role in gentamicin's toxic effects in vivo due to drug accumulation in pigmented tissues.
- Light-pigmented melanocytes exhibit higher sensitivity to the inhibitory effects of gentamicin on melanogenesis compared to dark-pigmented cells.
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