Miconazole and terbinafine induced reactive oxygen species accumulation and topical toxicity in human keratinocytes
| Autor: | M.-M. Wong, L.-K. Hung, P.-L. Lam, Roberto Gambari, L.-H. Yung, J. C.-O. Tang, P.-Y. Chung, K.-H. Lam, C.-H. Chui, Y.-W. Ho, R. S.-M. Wong, Wai Yeung Wong |
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| Rok vydání: | 2020 |
| Předmět: |
Keratinocytes
Miconazole Health Toxicology and Mutagenesis 010501 environmental sciences Pharmacology Toxicology medicine.disease_cause 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Humans Cytotoxicity Terbinafine 0105 earth and related environmental sciences chemistry.chemical_classification Reactive oxygen species Chemical Health and Safety integumentary system Superoxide Public Health Environmental and Occupational Health Hydrogen Peroxide General Medicine HaCaT chemistry Reactive Oxygen Species Wound healing 030217 neurology & neurosurgery Oxidative stress medicine.drug |
| Zdroj: | Drug and Chemical Toxicology. 45:834-838 |
| ISSN: | 1525-6014 0148-0545 |
| DOI: | 10.1080/01480545.2020.1778019 |
| Popis: | There are an estimated 1 billion cases of superficial fungal infection globally. Fungal pathogens form biofilms within wounds and delay the wound healing process. Miconazole and terbinafine are commonly used to treat fungal infections. They induce the accumulation of reactive oxygen species (ROS) in fungi, resulting in the death of fungal cells. ROS are highly reactive molecules, such as oxygen (O2), superoxide anion (O2•-), hydrogen peroxide (H2O2) and hydroxyl radicals (•OH). Although ROS generation is useful for killing pathogenic fungi, it is cytotoxic to human keratinocytes. To the best of our knowledge, the effect of miconazole and terbinafine on HaCaT cells has not been studied with respect to intracellular ROS stimulation. We hypothesized that miconazole and terbinafine have anti-wound healing effects on skin cells when used in antifungal treatment because they generate ROS in fungal cells. We used sulforhodamine B protein staining to investigate cytotoxicity and 2',7'-dichlorofluorescein diacetate to determine ROS accumulation at the 50% inhibitory concentrations of miconazole and terbinafine in HaCaT cells. Our preliminary results showed that topical treatment with miconazole and terbinafine induced cytotoxic responses, with miconazole showing higher cytotoxicity than terbinafine. Both the treatments stimulated ROS in keratinocytes, which may induce oxidative stress and cell death. This suggests a negative correlation between intracellular ROS accumulation in keratinocytes treated with miconazole or terbinafine and the healing of fungi-infected skin wounds. |
| Databáze: | OpenAIRE |
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