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Cytotoxic effects of topical antimicrobial and antiseptic agents on human keratinocytes in vitro
R G Teepe1, E J Koebrugge, C W Löwik
1Department of Dermatology, University Hospital, Leiden, The Netherlands.
Abstract:
The cytotoxicity of commonly used antimicrobial and antiseptic agents to cultured human keratinocytes was investigated, combining a morphologic assay with a quantitative neutral red (NR) spectrophotometric assay. Main outcome criteria of response were the initial cytotoxicity (NR 90) and midpoint cytotoxicity (NR 50) and the highest tolerated dose (HTD), a concentration causing the first observed morphologic alterations. These values were compared with commonly administered clinical doses or calculated doses. Thirty-five agents were evaluated; five agents were also subjected to an assay for cell morphologic alterations, and HTD and percentage of cells taking up trypan blue and annihilation dose were assessed. These studies show that in clinical concentrations many, but not all, agents exert profound cytotoxic effects. The results suggest that under certain conditions cultured epithelial grafts may be exposed to clinical concentrations of neomycin, clindamycin, framycetin, erythromycin, gentamicin, and 0.1% solutions of povidone-iodine. Tetrachlorodecaoxygen anion complex (TCDO) should be further evaluated as a likely effective cleansing agent before culture grafting.
Insights
Many common antimicrobial and antiseptic agents show significant cytotoxicity to human skin cells at clinical concentrations. Some agents, like neomycin and povidone-iodine, may be safe for cultured epithelial grafts under specific conditions.
Area of Science:
- Dermatology
- Cell Biology
- Toxicology
Background:
- Antimicrobial and antiseptic agents are widely used in clinical settings, particularly in wound care and dermatology.
- Assessing the safety of these agents on human skin cells is crucial for preventing adverse effects and optimizing treatment outcomes.
Purpose of the Study:
- To investigate the cytotoxicity of common antimicrobial and antiseptic agents on cultured human keratinocytes.
- To compare the cytotoxic effects of these agents at clinical concentrations with their highest tolerated doses (HTD).
Main Methods:
- A combination of morphologic and quantitative neutral red (NR) spectrophotometric assays was employed.
- Cytotoxicity was assessed using NR 90 (initial), NR 50 (midpoint), and HTD, alongside trypan blue uptake and annihilation dose for select agents.
- Thirty-five agents were evaluated, with five undergoing further detailed morphologic analysis.
Main Results:
- Many tested agents exhibited profound cytotoxic effects on human keratinocytes at clinically relevant concentrations.
- Specific agents, including neomycin, clindamycin, framycetin, erythromycin, gentamicin, and 0.1% povidone-iodine, were identified as potentially safe for cultured epithelial grafts under certain conditions.
- Tetrachlorodecaoxygen anion complex (TCDO) demonstrated potential as a cleansing agent for pre-culture grafting applications.
Conclusions:
- Clinical concentrations of numerous antimicrobial and antiseptic agents pose a significant risk of cytotoxicity to human keratinocytes.
- Several agents demonstrate a favorable safety profile for use with cultured epithelial grafts, warranting further clinical consideration.
- Tetrachlorodecaoxygen anion complex (TCDO) warrants further investigation as a promising agent for pre-culture graft preparation.