Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker

Jankovskaja, Skaidre; Engblom, Johan; Rezeli, Melinda; Markó-Varga, György; Ruzgas, Tautgirdas; Björklund, Sebastian

doi:10.1038/s41598-020-79903-w

Cited by 13 publications

(18 citation statements)

References 47 publications

(79 reference statements)

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“…Here, it can be noted that the results in Fig. 3 are in general agreement with the corresponding quantities obtained in our previous feasibility study (Jankovskaja et. al., 2021, unpublished results).…”

Section: Assessment Of the Capacities Of The Sampling Materials To Collect Analytessupporting

confidence: 90%

Non-invasive monitoring of low molecular weight biomarkers relevant to skin inflammation and cancer

Jankovskaja¹

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Development of skin inflammation and cancer in viable epidermis and dermis involve slow molecular weight (LMW) metabolites. We hypothesize that these LMW compounds can be collected on the surface of the skin and used for non-invasive diagnostics of skin disorders. Keeping in mind that substantial transdermal penetrationis achieved only for molecules of < 500 Da, we focused on topical monitoring of LMW biomarkers. In this thesis we investigated non-invasive, topical methods for monitoring LMW biomarkers by relevant in vitro and in vivo experiments. The LMW biomarkers were: - reactive oxygen species (ROS), specifically, hydrogen peroxide, H2O2 - amino acids and their derivatives, i.e., tryptophan (Trp), kynurenine (Kyn; a Trpderivative), phenylalanine (Phe), and tyrosine (Tyr; a Phe derivative). Initially, we have carried out in vitro experiments using dermatomed porcine skin and cell cultures. We characterized permeability of the biomarkers through skin and assessed methods of their monitoring. By using Prussian white particles, deposited on porcine skin, we demonstrated that hydrophilic biomarkers, such as H2O2, permeate the skin mainly through hair follicle pathways (Paper I). In paper II, we have showed that the enzymes transforming Trp to the inflammation and cancer biomarker Kyn, are expressed in the basal layer of epidermis. The magnitude of changes of the Trp/Kyn ratio in the cell culture model was assessed. In paper III, we have characterized Trp and Kyn permeability through skin in vitro, concluding that their permeabilities through stratum corneum are comparable. By in vivo experiments outlined in Paper IV, we have demonstrated the feasibility of topical, non-invasive sampling of Trp and Kyn, in relation to other amino acids. Kyn detection was compromised by its low abundance on the skin. In paper V, we performed a proof-of-concept study in vivo and confirmed that non-invasive sampling of Trp and amino acids of similar abundance, such as Phe and Tyr, is more robust. We concluded that Phe/Trp ratio might be equally good biomarker of skin disorders as a predicted Trp/Kyn ratio. Summarizing, the results of this thesis provide basic knowledge for deeper clinical studies of non-invasive, topical sampling of hydrophilic LMW biomarkers of skin inflammation and cancer.

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Section: Assessment Of the Capacities Of The Sampling Materials To Collect Analytessupporting

confidence: 90%

Non-invasive monitoring of low molecular weight biomarkers relevant to skin inflammation and cancer

Jankovskaja¹

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“…Further, it is well-known that the skin pH is an important factor for maintaining the integrity of the skin barrier. For example, it was shown by electrical impedance studies that treatment of the SC tissue for 24 h in a solution with pH 5.5 improves skin integrity, as judged from the observed increase in the skin membrane’s electrical resistance [ 51 ]. In contrast, the same treatment of the skin membrane in solutions with pH 7.4 and 8.8 resulted in a rather drastic decrease in the skin barrier’s resistance [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

“…For example, it was shown by electrical impedance studies that treatment of the SC tissue for 24 h in a solution with pH 5.5 improves skin integrity, as judged from the observed increase in the skin membrane’s electrical resistance [ 51 ]. In contrast, the same treatment of the skin membrane in solutions with pH 7.4 and 8.8 resulted in a rather drastic decrease in the skin barrier’s resistance [ 51 ]. On a molecular level, this can be explained in a similar manner as given above in connection to the keratinocytes.…”

Section: Discussionmentioning

confidence: 99%

“…On a molecular level, this can be explained in a similar manner as given above in connection to the keratinocytes. In other words, treatment in alkaline solutions modifies the charge status of the molecular components of the SC tissue, such as the fatty acids residing in the extracellular lipid matrix or titratable amino acid residues of the keratin filaments, which ultimately leads to swelling induced by electrostatic repulsion forces, loss of tissue integrity, and increased permeability characteristics [ 51 ]. In conclusion, the observed elevated effective catalase activity in the SC samples, after treatment in solution with increasing alkalinity, can therefore be explained by loss of SC tissue integrity, leading to improved substrate accessibility for catalase and overall increased transport characteristics of both H 2 O 2 and O 2 into and out of the SC tissue.…”

Section: Discussionmentioning

confidence: 99%

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Catalase Activity in Keratinocytes, Stratum Corneum, and Defatted Algae Biomass as a Potential Skin Care Ingredient

et al. 2021

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The generation of reactive oxygen species presents a destructive challenge for the skin organ and there is a clear need to advance skin care formulations aiming at alleviating oxidative stress. The aim of this work was to characterize the activity of the antioxidative enzyme catalase in keratinocytes and in the skin barrier (i.e., the stratum corneum). Further, the goal was to compare the activity levels with the corresponding catalase activity found in defatted algae biomass, which may serve as a source of antioxidative enzymes, as well as other beneficial algae-derived molecules, to be employed in skin care products. For this, an oxygen electrode-based method was employed to determine the catalase activity and the apparent kinetic parameters for purified catalase, as well as catalase naturally present in HaCaT keratinocytes, excised stratum corneum samples collected from pig ears with various amounts of melanin, and defatted algae biomass from the diatom Phaeodactylum tricornutum. Taken together, this work illustrates the versatility of the oxygen electrode-based method for characterizing catalase function in samples with a high degree of complexity and enables the assessment of sample treatment protocols and comparisons between different biological systems related to the skin organ or algae-derived materials as a potential source of skin care ingredients for combating oxidative stress.

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“…The formulations were applied for 2 h on 35 healthy subjects with the aim to collect tryptophan (Trp), tyrosine (Tyr), phenylalanine (Phe), and kynurenine (Kyn) as selected analytes. The reasoning for focusing on these molecules is, in brief, that Trp, Tyr, and Phe are known constituents of the so-called natural moisturizing factor (NMF) of the SC [32,33]. The NMF is a collection of osmotically active free amino acids, amino acid derivatives, and other small polar molecules and specific salts, which represents the biochemical basis for a healthy hydration status of the SC [32][33][34][35][36].…”

Section: Introductionmentioning

confidence: 99%

Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers—An Explorative In Vivo Study

et al. 2022

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The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

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Non-invasive skin sampling of tryptophan/kynurenine ratio in vitro towards a skin cancer biomarker

Cited by 13 publications

References 47 publications

Non-invasive monitoring of low molecular weight biomarkers relevant to skin inflammation and cancer

Non-invasive monitoring of low molecular weight biomarkers relevant to skin inflammation and cancer

Catalase Activity in Keratinocytes, Stratum Corneum, and Defatted Algae Biomass as a Potential Skin Care Ingredient

Hydrogels and Cubic Liquid Crystals for Non-Invasive Sampling of Low-Molecular-Weight Biomarkers—An Explorative In Vivo Study

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