Abstract
Thermal therapy has gained popularity over the years, and Portugal is one of the richest European countries in mineral therapeutic waters. The interest in the use of these natural mineral waters (NMW) for dermatologic purposes is continuously growing but there is a lack of scientific studies supporting its health benefits. The study aims to investigate the effect of a silica-rich NMW in skin cell homeostasis using two representative cell lines of the epidermis and dermis, keratinocytes and fibroblasts, respectively, in addition to a macrophage cell line. Mouse skin fibroblasts, macrophages and human keratinocytes were exposed to culture medium prepared with NMW. Cell metabolism (MTT or resazurin assays) and cell proliferation (trypan blue exclusion dye assay) were investigated. Migration (scratch-wound assay) and senescence (β-galactosidase activity assay) of fibroblasts were also studied. Exposure to NMW compromised the cell metabolic state of all the cell lines tested. This impairment was more pronounced in skin keratinocytes (60% reduction) relatively to skin fibroblasts (45% reduction) or macrophages (25% reduction). Proliferation of macrophages was reduced threefold upon exposure to thermal water, compared to controls. No differences were observed in migration between fibroblasts exposed to NMW and controls, while a potentiation of senescence of these cells was observed. Our results shed light in the bioactive effects of a silica-rich NMW supporting its therapeutic use. A reduction in both cell metabolism and proliferation of keratinocytes and macrophages supports the empirical clinical benefits of this NMW in hyperkeratotic conditions, such as psoriasis and atopic dermatitis.
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References
Almeida C, Madeira A, Marto J, Graça A, Pinto P, Ribeiro H (2019) Monfortinho thermal water-based creams: effects on skin hydration, psoriasis, and eczema in adults. Cosmetics 6:56. https://doi.org/10.3390/cosmetics6030056
Antonelli M, Donelli D, Fioravanti A (2018) Effects of balneotherapy and spa therapy on quality of life of patients with knee osteoarthritis: a systematic review and meta-analysis. Rheumatol Int 38:1807–1824
APHA (2005) Standard methods for the examination of water and wastewater, 21st edn. American Public Health Association, Washington, DC
Arasa J, Terencio MC, Andrés RM, Marín-Castejón A, Valcuende-Cavero F, Payá M, Montesinos MC (2019) Defective induction of COX-2 expression by psoriatic fibroblasts promotes pro-inflammatory activation of macrophages. Front Immunol 10. https://doi.org/10.3389/fimmu.2019.00536
Araujo ARTS, Sarraguça MC, Ribeiro MP, Coutinho P (2017) Physicochemical fingerprinting of thermal waters of Beira interior region of Portugal. Environ Geochem Health 39:483–496. https://doi.org/10.1007/s10653-016-9829-x
Aries MF, Hernandez-Pigeon H, Vaissière C, Delga H, Caruana A, Lévêque M, Bourrain M, Helffer KR, Chol B, Nguyen T, Bessou-Touya S, Castex-Rizzi N (2016) Anti-inflammatory and immunomodulatory effects of Aquaphilus dolomiae extract on in vitro models. Clin Cosmet Investig Dermatol 9:421–434. https://doi.org/10.2147/CCID.S113180
Benhadou F, Di M, Del Marmol V (2019) Psoriasis: keratinocytes or immune cells - which is the trigger? Dermatology 235:91–100
Berroth A, Kurschat N, Schwarz A, St F, Schwarz T, Wenck H, Neufang G (2013) Atopic dermatitis and skin disease role of fibroblasts in the pathogenesis of atopic dermatitis. J Allergy Clin Immunol 131:1547–1554.e6. https://doi.org/10.1016/j.jaci.2013.02.029
Cantista P (2008) O termalismo em Portugal. An Hidrol Medica 3:79–107
Cheleschi S, Gallo I, Tenti S (2020) A comprehensive analysis to understand the mechanism of action of balneotherapy: why, how, and where they can be used? Evidence from in vitro studies performed on human and animal samples. Int J Biometeorol 64:1247–1261
Coutinho P, Ribeiro M, Araujo A (2015) Dermatological potential of thermo-mineral waters from Beira Interior Region, Portugal. Conference Proceedings of 1st International Congress on Water: Healing SPA and Life Quality. http://hdl.handle.net/10314/2402. Accessed 6 Mar 2020
Diário da República (1989) Indicações Terapêuticas dos Estabelecimentos Termais Portugueses. In: Diário da Repúb. https://www.dgs.pt/saude-ambiental/areas-de-intervencao/estabelecimentos-termais/legislacao-indicacoes-terapeuticas.aspx. Accessed 6 Mar 2020
Diário da República (2008) Despacho n.º 8223/2008. In: Diário da Repub. https://dre.pt/application/conteudo/3651485. Accessed 6 Mar 2020
Faga A, Nicoletti G, Gregotti C, Finotti V, Nitto A, Gioglio L (2012) Effects of thermal water on skin regeneration. Int J Mol Med 29:732–740. https://doi.org/10.3892/ijmm.2012.917
Ferreira MO, Costa PC, Bahia MF (2010) Effect of São Pedro do sul thermal water on skin irritation. Int J Cosmet Sci 32:205–210. https://doi.org/10.1111/j.1468-2494.2010.00527.x
Ferreira R, Santos T, Cortes L, Cochaud S, Agasse F, Silva AP, Xapelli S, Malva JO (2012) Neuropeptide y inhibits interleukin-1 beta-induced microglia motility. J Neurochem 120:93–105. https://doi.org/10.1111/j.1471-4159.2011.07541.x
Fioravanti A, Cantarini L, Guidelli GM, Galeazzi M (2011) Mechanisms of action of spa therapies in rheumatic diseases: what scientific evidence is there? Rheumatol Int 31:1–8
Türsen B (2019) Water and Dermatology. In: França K (ed), Lotti T (ed) Advances in integrative dermatology, 1st edn. John Wiley & Sons Ltd, Hoboken, NJ, USA, pp 351-359
Gerencsér G, Szabó I, Szendi K, Hanzel A, Raposa B, Gyöngyi Z, Varga C (2019) Effects of medicinal waters on the UV-sensitivity of human keratinocytes – a comparative pilot study. Int J Biometeorol 63:1417–1423. https://doi.org/10.1007/s00484-019-01759-1
Gomes C, Rocha F, Silva E, Patinha C, Forjaz V, Terroso D (2010) Benefits of Mud / Clay and Thermal Spring Water in the human heath. Conference Proceedings of environment 2010: situation and perspectives for the European Union. https://www.semanticscholar.org/paper/Benefits-of-Mud-%2F-Clay-and-Thermal-Spring-Water-in-Gomes-Silva/13321364da6da78fd3517191edbdf78241f2ef9f. Accessed 22 Oct 2018
Gubán B, Vas K, Balog Z, Manczinger M, Bebes A, Groma G, Széll M, Kemény L, Bata-Csörgö Z (2016) Abnormal regulation of fibronectin production by fibroblasts in psoriasis. Br J Dermatol 174:533–541. https://doi.org/10.1111/bjd.14219
Hercogova J, Stanghellini E, Tsoureli-Nikita E, Menchini G (2002) Inhibitory effects of Leopoldine spa water on inflammation caused by sodium lauryl sulphate. J Eur Acad Dermatol Venereol 16:263–266. https://doi.org/10.1046/j.1468-3083.2002.00451.x
INFARMED - Instituto Nacional da Farmácia e do Medicamento (2009) Farmacopeia portuguesa 9. INFARMED, Lisboa
Joly F, Galoppin L, Bordat P, Cousse H, Neuzil E (2000) Calcium and bicarbonate ions mediate the inhibition of mast cell histamine release by Avène spa water. Fundam Clin Pharmacol 14:611–613. https://doi.org/10.1111/j.1472-8206.2000.tb00447.x
Lee HP, Choi YJ, Cho KA, Woo SY, Yun ST, Lee JT, Kim HJ, Lee KH, Kim JW (2012) Effect of spa spring water on cytokine expression in human keratinocyte HaCaT cells and on differentiation of CD4+T cells. Ann Dermatol 24:324–336. https://doi.org/10.5021/ad.2012.24.3.324
Leite Dantas R, Masemann D, Schied T, Bergmeier V, Vogl T, Loser K, Brachvogel B, Varga G, Ludwig S, Wixler V (2016) Macrophage-mediated psoriasis can be suppressed by regulatory T lymphocytes. J Pathol 240:366–377. https://doi.org/10.1002/path.4786
Li J, Li X, Hou R, Liu R, Zhao X, Dong F, Wang C, Yin G, Zhang K (2015) Psoriatic T cells reduce epidermal turnover time and affect cell proliferation contributed from differential gene expression. J Dermatol 42:874–880. https://doi.org/10.1111/1346-8138.12961
Matz H, Orion E, Wolf R (2003) Balneotherapy in dermatology. Dermatol Ther 16:132–140. https://doi.org/10.1046/j.1529-8019.2003.01622.x
Moura LI, Cruz MT, Carvalho E (2013) The effect of neurotensin in human keratinocytes - implication on impaired wound healing in diabetes. Exp biol med (Maywood):6–12. https://doi.org/10.1177/1535370213510665
Nedoszytko B, Sokołowska-Wojdyło M, Ruckemann-Dziurdzińska K, Roszkiewicz J, Nowicki RJ (2014) Chemokines and cytokines network in the pathogenesis of the inflammatory skin diseases: atopic dermatitis, psoriasis and skin mastocytosis. Postep Dermatologii i Alergol 31:84–91
Nicoletti G, Saler M, Pellegatta T, Malovini A, Faga A, Scalise A, Riva F (2016) Effects of a spring water on human skin fibroblast in vitro cultures: Preliminary results. Acta Vulnologica 14:196–201
Nicoletti G, Saler M, Pellegatta T, Tresoldi M, Bonfanti V, Malovini A, Faga A, Riva F (2017) Ex vivo regenerative effects of a spring water. Biomed Rep 7:508–514. https://doi.org/10.3892/br.2017.1002
Nicoletti G, Saler M, Tresoldi MM, Faga A, Benedet M, Cristofolini M (2019) Regenerative effects of spring water-derived bacterial lysates on human skin fibroblast in in vitro culture: preliminary results. J Int Med Res 47:5777–5786. https://doi.org/10.1177/0300060519880371
Nunes S, Tamura B (2012) Revisão histórica das águas termais. Surg Cosmet Dermatol 3:252–258
O’Brien J, Wilson I, Orton T, Pognan F (2000) Investigation of the Alamar blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 267:5421–5426. https://doi.org/10.1046/j.1432-1327.2000.01606.x
Oliveira AS, Vaz CV, Silva A, Ferreira SS, Correia S, Ferreira R, Breitenfeld L, Martinez-de-Oliveira J, Palmeira-de-Oliveira R, Pereira C, Cruz MT, Palmeira-de-Oliveira A (2019) Chemical signature and antimicrobial activity of Central Portuguese Natural Mineral Waters against selected skin pathogens. Environ Geochem Health 6:2057. https://doi.org/10.1007/s10653-019-00473-6
Proksch E (2018) Buffering capacity. Curr Probl Dermatology 54:11–18. https://doi.org/10.1159/000489513
Quattrini S, Pampaloni B, Brandi ML (2016) Natural mineral waters: chemical characteristics and health effects. Clin Cases Miner Bone Metab 13:173. https://doi.org/10.11138/CCMBM/2016.13.3.173
Rebelo M, da Silva EF, Rocha F (2015) Characterization of Portuguese thermo-mineral waters to be applied in peloids maturation. Environ Earth Sci 73:2843–2862. https://doi.org/10.1007/s12665-014-3670-2
Riyaz N, Arakkal FR (2011) Spa therapy in dermatology. Indian J Dermatol Venereol Leprol 77:128–134. https://doi.org/10.4103/0378-6323.77450
Sukenik S, Flusser D, Abu-Shakra M (1999) The role of Spa therapy in various rheumatic diseases. Rheum Dis Clin N Am 25:883–897. https://doi.org/10.1016/S0889-857X(05)70108-3
Valitutti S, Castellino F, Musiani P (1990) Effect of sulfurous (thermal) water on T lymphocyte proliferative response. Ann Allergy 65:463–468
Varga C (2019) To treat or not to treat? Misbeliefs in spa water disinfection. Int J Biometeorol 63:1135–1138. https://doi.org/10.1007/s00484-019-01722-0
Wang AS, Dreesen O (2018) Biomarkers of cellular senescence and skin aging. Front Genet 9:247
Zöller N, Valesky E, Hofmann M, Bereiter-Hahn J, Bernd A, Kaufmann R, Meissner M, Kippenberger S (2015a) Impact of different spa waters on inflammation parameters in human keratinocyte HaCaT cells. Ann Dermatol 27:709–714. https://doi.org/10.5021/ad.2015.27.6.709
Zöller N, Valesky E, Hofmann M, Bereiter-Hahn J, Bernd A, Kaufmann R, Meissner M, Kippenberger S (2015b) Impact of different spa waters on inflammation parameters in human keratinocyte HaCaT cells. Ann Dermatol 27:709–714. https://doi.org/10.5021/ad.2015.27.6.709
Acknowledgements
The authors would like to thank Monfortinho Thermal Centre for participating in this study. The authors acknowledge financial support provided by FEDER - European Regional Development Fund, through the POCI-COMPETE 2020 - Operational Programme Competitiveness and Internationalization in Axis I - Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491); National Funds by FCT - Foundation for Science and Technology (Project UIDB/00709/2020); and Provere Termas Centro – Projeto Âncora de Inovação, co-funded by Centro 2020, Portugal 2020 and European Union funds (PROVERE CENTRO-04-3928-FEDER-000010).
Funding
POCI-COMPETE 2020- Operational Programme Competitiveness and Internationalization in Axis I - Strengthening research, technological development and innovation (Project POCI-01-0145-FEDER-007491).
FCT - Foundation for Science and Technology (Project UIDB/00709/2020).
Provere Termas Centro – Projeto Âncora de Inovação, co-funded by Centro 2020, Portugal 2020 and European Union funds (PROVERE CENTRO-04-3928-FEDER-000010).
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ASO performed the experiments, assembled and analysed the data, and wrote the manuscript. CVV and AS collaborated in the acquisition and assembly of data and critically revised the manuscript. SC, RF, LB, JMO, RPO and CP contributed to experimental conception and design, and critical reading and editing of the manuscript. MTC and APO contributed to experimental conception and design, data analysis and interpretation and revised the manuscript critically for important intellectual content.
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Oliveira, A.S., Vaz, C.V., Silva, A. et al. In vitro evaluation of potential benefits of a silica-rich thermal water (Monfortinho Thermal Water) in hyperkeratotic skin conditions. Int J Biometeorol 64, 1957–1968 (2020). https://doi.org/10.1007/s00484-020-01986-x
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DOI: https://doi.org/10.1007/s00484-020-01986-x