Smart Fluids As Autophagy-Activating Photoprotectors: In Vitro Analysis of Dead Sea Water and Magnetized Saline Water Against Ultraviolet B (UVB)-Induced Photodamage in Human Keratinocytes.

Background Autophagy induction has been shown to mitigate both ultraviolet B (UVB)-induced DNA damage and inflammation. Smart fluids, including Dead Sea water (DSW) and saline magnetized water (MW), have recently been suggested to promote autophagy activation. This in vitro study was designed to investigate the ability of DSW and saline MW to inhibit the formation of UVB-induced cyclobutane pyrimidine dimers (CPDs) and the expression of the NOD-like receptor protein 3 (NLRP3) inflammasome in UVB-irradiated HaCaT cells, a well-established, spontaneously immortalized human keratinocyte cell line. Methods To explore whether autophagy mediated the photoprotection induced by smart fluids, we measured two established autophagy markers (beclin-1 and LC3B) in HaCaT cell lysates and examined how wortmannin, an autophagy inhibitor, modulated the smart fluids' effects on post-irradiation CPDs and NLRP3 inflammasome levels. Results Compared to unirradiated control cells not exposed to any fluid (set at 1 a.u.), pretreatment with DSW (15.7 ± 1.9 a.u.) and saline MW (11.3 ± 1.6 a.u.) markedly reduced CPD formation in UVB-irradiated cells compared to two control fluids (saline non-MW: 20.9 ± 0.8 a.u.; distilled water: 21.4 ± 0.6 a.u.) (all p < 0.001). Notably, among the two smart fluids, saline MW significantly outperformed DSW in terms of DNA protection (p < 0.001). Conversely, DSW and saline MW demonstrated no statistically significant difference in NLRP3 inflammasome inhibition (p = 0.56). Both smart fluids effectively attenuated the UVB-induced decrease in beclin-1 and LC3B (all < 0.001), although the observed effects were significantly more pronounced for saline MW (both p < 0.05). Notably, wortmannin either partially (CPDs) or completely (NLRP3 inflammasome) abrogated the photoprotective effects of both DSW and saline MW, suggesting that the observed chemopreventive properties were mainly attributable to their action as autophagy activators. Conclusions Our findings support the potential application of DSW and saline MW as sustainable active ingredients in topical skin products aimed at preventing UVB-induced non-melanoma skin cancers and cutaneous inflammaging.