Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen.
Extracts of Hypericum perforatum (St. John's wort) are used in the treatment of depression. They contain the plant pigment hypericin and hypericin derivates. These compounds have light-dependent activities. In order to estimate the potential risk of phototoxic skin damage during antidepressive therapy, we investigated the phototoxic activity of hypericin extract using cultures of human keratinocytes and compared it with the effect of the well-known phototoxic agent psoralen. The absorbance spectrum of our Hypericum extract revealed maxima in the whole UV range and in parts of the visible range. We cultivated human keratinocytes in the presence of different Hypericum concentrations and irradiated the cells with 150 mJ/cm2 UVB, 1 J/cm2 UVA or 3 h with a white light of photon flux density 2.6 mumol m-2 s-1. The determination of the bromodeoxyuridine incorporation rate showed a concentration- and light-dependent decrease in DNA synthesis with high hypericin concentrations (> or = 50 micrograms/mL) combined with UVA or visible light radiation. In the case of UVB irradiation a clear phototoxic cell reaction was not detected. We found phototoxic effects even with 10 ng/mL psoralen using UVA with the same study design as in the case of the Hypericum extract. These results confirm the phototoxic activity of Hypericum extract on human keratinocytes. However, the blood levels that are to be expected during antidepressive therapy are presumably too low to induce phototoxic skin reactions.
Department of Dermatology, Clinical Hospital of the J. W. Goethe University, Frankfurt, Germany. bernd@em.uni-frankfurt.de
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A
Bernd
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Simon
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Ramirez Bosca
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Kippenberger
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Diaz Alperi
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Miquel
J F
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Villalba Garcia
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Pamies Mira
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Kaufmann
D000928:Antidepressive Agents / Q000009:adverse effects*; D002478:Cells, Cultured; D017484:Dermatitis, Phototoxic; D005363:Ficusin / Q000009:adverse effects*; D006801:Humans; D020902:Hypericum; D015603:Keratinocytes / Q000187:drug effects*; D010569:Perylene / Q000009:adverse effects / Q000031:analogs & derivatives*; D017319:Photosensitizing Agents / Q000009:adverse effects*; D010936:Plant Extracts / Q000633:toxicity*; D010946:Plants, Medicinal; D011794:Quercetin / Q000009:adverse effects / Q000031:analogs & derivatives*; D013054:Spectrophotometry, Atomic; D014466:Ultraviolet Rays; D014966:Xanthenes / Q000009:adverse effects*
D000928:Antidepressive Agents; D017319:Photosensitizing Agents; D010936:Plant Extracts; D014966:Xanthenes; D010569:Perylene; D011794:Quercetin; D005363:Ficusin