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Melanocyte melanin augments sparfloxacin-induced phototoxicity
H Hamanaka1, H Mizutani, K Asahig
1Department of Dermatology, Mie University, Faculty of Medicine, Tsu, Japan.
Abstract:
Quinolone has become one of the common causative agents of drug-induced photosensitive dermatitis, and its phototoxicity has now become a clinical issue. The mechanisms of long-lasting phototoxicity induced by sparfloxacin (SPFX) were investigated using melanotic and amelanotic melanoma cell lines. The sensitivities to SPFX and UVA irradiation up to 6 J/cm2 of both cells were not significantly different. However, the melanotic melanoma cell cultured with 1-150 microg/ml of SPFX showed significantly higher sensitivity to UVA irradiation compared with that of the amelanotic melanoma cell. By pulse culture with SPFX, the bound SPFX level of melanotic cell line was 10-20 times higher than that of the amelanotic cell line. These data strongly suggest that the melanin in melanocytes and keratinocytes accumulates the antibacterial quinolone and increases its tissue concentration in the basal epidermis and contributes to the long-lasting photo-injury and liquefaction degeneration of the basal cells in antibiotic quinolone phototoxic dermatitis.
Insights
Melanin accumulation in skin cells significantly increases phototoxicity from quinolone antibiotics like sparfloxacin (SPFX). This explains long-lasting skin damage in drug-induced photosensitive dermatitis.
Area of Science:
- Dermatology
- Pharmacology
- Cell Biology
Background:
- Quinolones are common causes of drug-induced photosensitive dermatitis, presenting a clinical challenge.
- The mechanisms underlying persistent phototoxicity from quinolone antibiotics require further investigation.
Purpose of the Study:
- To investigate the mechanisms of long-lasting phototoxicity induced by sparfloxacin (SPFX).
- To compare the phototoxic effects of SPFX in melanotic and amelanotic melanoma cells.
Main Methods:
- Utilized melanotic and amelanotic melanoma cell lines for comparative analysis.
- Assessed cell sensitivity to sparfloxacin (SPFX) and UVA irradiation.
- Quantified bound SPFX levels in cell lines after pulse culture.
Main Results:
- Melanotic and amelanotic cells showed similar sensitivity to SPFX and UVA alone.
- Melanotic cells exhibited significantly higher sensitivity to UVA when pre-treated with SPFX.
- Bound SPFX levels were 10-20 times higher in melanotic cells compared to amelanotic cells.
Conclusions:
- Melanin accumulation in skin cells enhances tissue concentration of antibacterial quinolones.
- This increased concentration contributes to long-lasting photo-injury and basal cell degeneration in quinolone-induced phototoxic dermatitis.