The absorption of polycyclic aromatic hydrocarbons into the skin to elicit cutaneous inflammation: The establishment of structure–permeation and in silico–in vitro–in vivo relationships

Ahmed Alalaiwe, Yin Ku Lin, Chih Hung Lin, Pei Wen Wang, Jie Yu Lin, Jia You Fang*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

21 Scopus citations

Abstract

Polycyclic aromatic hydrocarbons (PAHs) can induce skin toxicity. Although some investigations have been conducted to assess the skin toxicity of different PAHs, few comparisons using a series of PAHs with different ring numbers and arrangements have been done. We aimed to explore the skin absorption of 6 PAH compounds and their effect on cutaneous inflammation. In vitro skin permeation was rated by Franz cell with pig skin. Molecular docking was employed to compute the PAH interaction with stratum corneum (SC) lipids. Cultured keratinocytes were exposed to PAHs for analyzing cytotoxicity, cyclooxygenase (COX)-2, prostaglandin E2 (PGE2), chemokines, and differentiation proteins. The in vivo topical PAH exposure in mice was characterized by skin absorption, transepidermal water loss (TEWL), PGE2 level, and histology. The skin deposition from the aqueous vehicle increased following the increase of PAH lipophilicity and molecular size, with benzo[a]pyrene (5-ring PAH) showing the greatest absorption. Pyrene was the compound showing the highest penetration across the skin (flux). Although the PAHs fluoranthene, pyrene, chrysene, and 1,2-benzanthracene all had 4 rings, the skin permeation was quite different. 1,2-Benzanthracene showed the greatest absorption among the 4-ring compounds. The PAHs with higher absorption exhibited stronger interaction with SC lipids according to the in silico modeling. Chrysene and 1,2-benzanthracene generally showed the highest COX-2 and PGE2 expression, followed by benzo[a]pyrene. The lowest COX-2 and PGE2 upregulation was observed for naphthalene (2-ring PAH). A contrary tendency was detected for the upregulation of chemokines. Filaggrin and integrin β1 in keratinocytes were suppressed at a comparable level by all PAHs. The skin's absorption of PAHs showed strong in vivo–in vitro correlation. 1,2-Benzanthracene and benzo[a]pyrene highly disrupted the skin barrier and elevated the inflammation in vivo. The tendency toward in vivo inflammation caused by various PAHs could be well predicted by the combined estimation using in vitro skin absorption and a keratinocyte bioassay. This study also established the structure–permeation relationship (SPR) of PAHs.

Original languageEnglish
Article number126955
JournalChemosphere
Volume255
DOIs
StatePublished - 09 2020

Bibliographical note

Publisher Copyright:
© 2020 Elsevier Ltd

Keywords

  • Inflammation
  • Keratinocyte
  • Polycyclic aromatic carbon
  • Skin absorption
  • Skin barrier function
  • Structure-permeation relationship

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