Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: role of Nrf2-dependent gene expression and antioxidant enzymes.
Level 5 - mechanism / opinion, no new human data
Preclinical bench research using in vitro cell cultures and ex vivo human skin explants.
PubMed 24121007 · doi:10.1016/j.phrs.2013.09.009
What was done
Researchers tested the protective effects of sulforaphane (SFN) and phenylethyl isothiocyanate (PEITC) against ultraviolet radiation (UVR, 300 mJ/cm²) using in vitro cultured human HaCaT keratinocytes and ex vivo human full-thickness skin explants. In HaCaT cells, they evaluated Nrf2 transactivation and the gene expression of phase II antioxidant enzymes: γ-glutamylcysteine-synthetase (γGCS), heme oxygenase 1 (HO-1), and NAD(P)H quinone oxidoreductase 1 (NQO1). In ex vivo skin pretreated with SFN or PEITC (5 μM and 10 μM), they measured expression of these enzymes and catalase, alongside histological counts of sunburn cells, catalase levels, and cleaved caspase-3 activation via immunofluorescence.
What was found
UVR exposure (300 mJ/cm²) of human skin significantly increased sunburn cell counts and caspase-3 activation for up to 48 hours (p < 0.001) while significantly reducing catalase levels (p < 0.001). Pretreatment with 5 μM and 10 μM SFN and PEITC significantly counteracted these effects. Both compounds increased Nrf2 activity and upregulated γGCS, HO-1, and NQO1 gene expression in HaCaT cells, with corresponding mRNA increases observed in human full-thickness skin.
Why it matters
This study provides mechanistic evidence that activating the Nrf2 pathway with dietary isothiocyanates can bolster endogenous antioxidant defenses and limit UV-induced apoptosis in human skin tissue. It supports further translational research into topical or dietary isothiocyanates for photoprotection.
Limits
The study is restricted to cell culture and ex vivo tissue models without in vivo human validation. The abstract omits sample size (number of skin donors), exact numerical effect sizes (reporting only p-values), and treatment exposure durations.
Cited by
- context Phenethyl isothiocyanate (PEITC) from watercress acts synergistically with sulforaphane to stimulate NRF2 five times more than sulforaphane alone.