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  • 1
    Online Resource
    Online Resource
    Cis‐urocanic acid suppresses UV‐B‐induced interleukin‐6 secretion and cytotoxicity in human corneal and conjunctival epithelial cells in vitro
    Wiley ; 2009
    In:  Acta Ophthalmologica Vol. 87, No. s244 ( 2009-09), p. 0-0
    Details
    In: Acta Ophthalmologica, Wiley, Vol. 87, No. s244 ( 2009-09), p. 0-0
    Abstract: Purpose Urocanic acid (UCA) is a major UV‐absorbing endogenous chromophore in the epidermis and is also an efficacious immunosuppressant. The anti‐inflammatory and cytoprotective effects of cis‐UCA were studied in ocular surface cell cultures exposed to UV‐B irradiation. Methods Human corneal epithelial cells (HCE‐2) and human conjunctival epithelial cells (HCEC) were incubated with 10, 100, 1000, and 5000 µg/ml cis‐UCA with and without a single UV‐B irradiation dose. Cell viability was measured by the colorimetric MTT (3‐(4,5‐dimethyldiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay. Results The UV‐B irradiation elevated IL‐6 secretion by 7 to 9‐fold in HCE‐2 cells and by 2‐fold in HCEC cells as analyzed with ELISA., declined by 30 to 50 % in HCE‐2 cells and by 20 to 40 % in HCEC cells after UVB irradiation. Treatment with 100 µg/ml cis‐UCA completely prevented both the elevated IL‐6 secretion and the decrease in cell viability to the same level as nonirradiated control cells in both cell types, i.e. simultaneous anti‐inflammatory and cytoprotective effects against UV‐B radiation.No significant effects on IL‐6 secretion or viability of the nonirradiated cells were observed with 10 and 100 µg/ml cis‐UCA, while 1000 µg/ml cis‐UCA evoked secretion of IL‐6 in both cell types. The 5000 µg/ml concentration was toxic. Conclusion Cis‐UCA may represent a promising anti‐inflammatory and cytoprotective treatment option to suppress UV‐B‐induced inflammation and cellular damage in human corneal and conjunctival epithelial cells.
    Type of Medium: Online Resource
    ISSN: 1755-375X , 1755-3768
    URL: Issue
    URL: Article
    DOI: 10.1111/aos.2009.87.issue-s244
    DOI: 10.1111/j.1755-3768.2009.271.x
    Language: English
    Publisher: Wiley
    Publication Date: 2009
    detail.hit.zdb_id: 2466981-7
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  • 2
    Online Resource
    Online Resource
    Cis‐urocanic acid inhibits SAPK/JNK signaling pathway in UV‐B exposed human corneal epithelial cells in vitro
    Wiley ; 2011
    In:  Acta Ophthalmologica Vol. 89, No. s248 ( 2011-09), p. 0-0
    Details
    In: Acta Ophthalmologica, Wiley, Vol. 89, No. s248 ( 2011-09), p. 0-0
    Abstract: Purpose Urocanic acid (UCA) is a major endogenous UV‐absorbing chromophore in the epidermis and it is also an efficacious immunosuppressant. The effects of cis‐UCA on UV‐B‐induced inflammatory and apoptotic responses in HCE‐2 cells, focusing on the nuclear factor kappa B (NF‐kappaB) and AP‐1 signalling pathways were studied. Methods After exposing HCE‐2 cells to UV‐B and cis‐UCA, the DNA binding of c‐Fos, c‐Jun and NF‐kappaB were measured with ELISA. In addition, the endogenous levels of phosphorylated stress‐activated protein kinase/c‐Jun N‐terminal kinase (phospho‐SAPK/JNK and phospho‐c‐Jun were determined. The proliferative capacity of HCE‐2 cells was also quantified, and the cytotoxicity of the cis‐UCA and UV‐B treatments was monitored by measuring the release of lactate dehydrogenase enzyme in the culture medium. Results UV‐B irradiation induced the binding of transcription factors c‐Jun, c‐Fos, and NF‐kappaB to DNA. Cis‐UCA inhibited the binding of c‐Jun and c‐Fos but not that of NF‐κB. Moreover, UV‐B increased the levels of phospho‐c‐Jun and phospho‐JNK, and the expression of both was attenuated by cis‐UCA. Cis‐UCA also alleviated the UV‐B‐induced apoptosis and proliferative decline in human corneal cells. Conclusion The results from this study suggest that cis‐UCA suppresses JNK signaling pathway, which provides potential for treating UV‐B‐induced inflammatory defects in human corneal cells.
    Type of Medium: Online Resource
    ISSN: 1755-375X , 1755-3768
    URL: Issue
    URL: Article
    DOI: 10.1111/j.1755-3768.2011.issue-s246
    DOI: 10.1111/j.1755-3768.2011.3135.x
    Language: English
    Publisher: Wiley
    Publication Date: 2011
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  • 3
    Online Resource
    Online Resource
    Cis‐urocanic acid inhibits conjunctivitis and blepharitis in rat model of acute eye irritation
    Wiley ; 2012
    In:  Acta Ophthalmologica Vol. 90, No. s249 ( 2012-09), p. 0-0
    Details
    In: Acta Ophthalmologica, Wiley, Vol. 90, No. s249 ( 2012-09), p. 0-0
    Abstract: Purpose In vitro studies have shown anti‐inflammatory and cytoprotective effects of cis‐urocanic acid (cis‐UCA) in human ocular epithelial cells exposed to UV‐B irradiation. In this study, we aimed to investigate the efficacy of topical cis‐UCA against compound 48/80 induced eye irritation in a rat model. Methods Adult Wistar rats in groups of six animals were treated with 1000 µg/ml compound 48/80 in both eyes. Cis‐UCA 0.5% solution, corticosteroid dexamethasone 1 mg/ml (Oftan® Dexa), antihistamine ketotifen 0.25 mg/ml (Zaditen), or PBS was applied in both eyes at time points 0.5, 6, and 12 h after application of compound 48/80. Clinical signs of ocular inflammation were evaluated by scoring from photographs by ophthalmologist 1, 6, 12, and 24 h after the last drug application. Results Cis‐UCA solution attenuated conjunctival hyperemia in compound 48/80 irritated eyes equally well compared to dexamethasone and ketotifen. At time points 12 and 24 h, the mean decrease in severity score was 50% and 40%, respectively, for the cis‐UCA group. Redness of the eyelid margin was prevented best by ketotifen at 1‐h time point, whereas cis‐UCA and dexamethasone almost completely abolished lid redness at 6, 12, and 24 h. Conclusion These results suggest that cis‐UCA has an anti‐inflammatory effect in acute eye irritation, which is comparable to corticosteroid dexamethasone and antihistamine ketotifen.
    Type of Medium: Online Resource
    ISSN: 1755-375X , 1755-3768
    URL: Issue
    URL: Article
    DOI: 10.1111/j.1755-3768.2012.issue-s249
    DOI: 10.1111/j.1755-3768.2012.2632.x
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2466981-7
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  • 4
    Online Resource
    Online Resource
    Cis‐urocanic acid eye drops are safe and well tolerated in healthy adults – results from a randomised phase 1 clinical study
    Wiley ; 2012
    In:  Acta Ophthalmologica Vol. 90, No. s249 ( 2012-09), p. 0-0
    Details
    In: Acta Ophthalmologica, Wiley, Vol. 90, No. s249 ( 2012-09), p. 0-0
    Abstract: Purpose Cis‐urocanic acid (cis‐UCA) is an endogenous small molecule of the skin. Preclinical data suggest that topical cis‐UCA could be used as an anti‐inflammatory treatment in ophthalmology. We investigated the safety, tolerability and pharmacokinetics (PK) of cis‐UCA in healthy adults in a randomised, double‐blind and placebo‐controlled phase 1 study. Methods The 37 subjects in 3 groups received either 0.5% or 2.5% cis‐UCA eye drops, or placebo. In part I, the eye drops were administered on one eye 3x in one day. In part II, the same subjects received the same eye drops on both eyes 3x a day for 14 days. Clinical evaluations included complete physical examination and safety laboratory tests, physical examination of the eyes, and ocular comfort rating by 5 parameters. Results Both cis‐UCA eye drops were safe and well tolerated throughout the study. None of the ocular safety parameters differed between cis‐UCA and placebo. Of the ocular comfort rating, only burning of the eyes was significantly higher with cis‐UCA than with placebo; however, this reaction was mild, transient and infrequent in all cases. PK analysis showed that 2.5% cis‐UCA eye drops may be absorbed after repeated ocular dosing, as 7/12 subjects in this group had low cis‐UCA levels ( 〈 10 µg/ml) in the urine. However, plasma cis‐UCA levels were negligible. Conclusion The observed good local and systemic safety and tolerability of cis‐UCA eye drops warrants further clinical studies in patients with inflammatory ocular diseases. Commercial interest
    Type of Medium: Online Resource
    ISSN: 1755-375X , 1755-3768
    URL: Issue
    URL: Article
    DOI: 10.1111/j.1755-3768.2012.issue-s249
    DOI: 10.1111/j.1755-3768.2012.T104.x
    Language: English
    Publisher: Wiley
    Publication Date: 2012
    detail.hit.zdb_id: 2466981-7
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