Development of novel <i>in vitro</i> photosafety assays focused on the Keap1–Nrf2–ARE pathway

Tsujita-Inoue, Kyoko; Hirota, Morihiko; Atobe, Tomomi; Ashikaga, Takao; Tokura, Y.; Kouzuki, Hirokazu

doi:10.1002/jat.3234

Cited by 12 publications

(6 citation statements)

References 39 publications

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“…A novel in vitro photosafety assay was developed to evaluate potential photoallergens and phototoxicants using AREc32 and KeratinoSens reporter cell lines [231] . Chemicals that are photoallergens/photoxicans activate the Keap1-Nrf2-ARE pathway when exposed to UV radiation.…”

Section: Applications Based On Aresmentioning

confidence: 99%

Antioxidant response elements: Discovery, classes, regulation and potential applications

et al. 2018

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Exposure to antioxidants and xenobiotics triggers the expression of a myriad of genes encoding antioxidant proteins, detoxifying enzymes, and xenobiotic transporters to offer protection against oxidative stress. This articulated universal mechanism is regulated through the cis-acting elements in an array of Nrf2 target genes called antioxidant response elements (AREs), which play a critical role in redox homeostasis. Though the Keap1/Nrf2/ARE system involves many players, AREs hold the key in transcriptional regulation of cytoprotective genes. ARE-mediated reporter constructs have been widely used, including xenobiotics profiling and Nrf2 activator screening. The complexity of AREs is brought by the presence of other regulatory elements within the AREs. The diversity in the ARE sequences not only bring regulatory selectivity of diverse transcription factors, but also confer functional complexity in the Keap1/Nrf2/ARE pathway. The different transcription factors either homodimerize or heterodimerize to bind the AREs. Depending on the nature of partners, they may activate or suppress the transcription. Attention is required for deeper mechanistic understanding of ARE-mediated gene regulation. The computational methods of identification and analysis of AREs are still in their infancy. Investigations are required to know whether epigenetics mechanism plays a role in the regulation of genes mediated through AREs. The polymorphisms in the AREs leading to oxidative stress related diseases are warranted. A thorough understanding of AREs will pave the way for the development of therapeutic agents against cancer, neurodegenerative, cardiovascular, metabolic and other diseases with oxidative stress.

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Section: Applications Based On Aresmentioning

confidence: 99%

Antioxidant response elements: Discovery, classes, regulation and potential applications

et al. 2018

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“…As the alternative in vitro skin sensitization method integrates the results of multiple alternative methods involving different key events, the photo‐antioxidant response element (photo‐ARE) assay for key event 2 (Tsujita‐Inoue et al, ), photo‐hCLAT for key event 3 (Toyoda & Itagaki, ) and photo‐ADRA were compared. Photo‐hCLAT could not be compared because of the small number of chemicals evaluated for photoallergy.…”

Section: Discussionmentioning

confidence: 99%

“…Photo‐hCLAT could not be compared because of the small number of chemicals evaluated for photoallergy. Using the photo‐ARE assay, Tsujita‐Inoue et al () evaluated photoallergy potential of 30 chemicals, 26 of which were common with photo‐ADRA. p ‐Phenylenediamine contained in 26 chemicals was judged negative by photo‐ADRA; however, the average value of depletion measured by normal ADRA without photoirradiation was already 86% and the depletion value was already high before photoirradiation.…”

Section: Discussionmentioning

confidence: 99%

Development of photo‐amino acid derivative reactivity assay: a novel in chemico alternative method for predicting photoallergy

Yamamoto

Fujita

Wanibuchi

et al. 2020

J of Applied Toxicology

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Photoallergy test of cosmetics and several types of pharmaceutical substances is often necessary for obtaining approval from authorities. However, there are no official test guidelines for photoallergy evaluation. Therefore, we tried to establish a photoallergy test by utilizing an in chemico alternative sensitization method, amino acid derivative reactivity assay (ADRA). To determine the criteria for judging the photoallergy potential, photo-ADRA with or without photoirradiation was performed using 60 photoallergenic chemicals, and cysteine and lysine derivatives were detected using high-performance liquid chromatography either by absorbance or fluorescence measurement. The accuracy of prediction was 81.4% (48 of 59) and 80.0% (48 of 60) using the absorbance and fluorescence methods, respectively. However, as chemicals can breakdown into multiple chemicals during photoirradiation, the absorbance method often cannot perform accurate detection due to co-elution, whereas the fluorescence method can do this due to lack of co-elution. Moreover, all eight chemicals that were found to be negative or false-positive for photoirritation in the 3T3 neutral red uptake phototoxicity test were confirmed as positive for photoallergy using this method. Furthermore, we prepared three types of pseudo-mixtures where we added one photoallergen along with five nonphotoallergens and performed the photo-ADRA by the ultraviolet and fluorescence methods. The result of the fluorescence method was almost the same as that obtained with the use of a single photoallergen and hence the outcome was not affected by the mixture. Thus, this study not only showed a method of evaluating the photoallergy potential of a single chemical but also a mixture, making it useful as an in chemico photoallergy alternative test.

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“…In vitro skin sensitization ARE-Nrf2 luciferase test, a reporter gene assay using the KeratinoSensTM test method (reporter cell line), measuring cell culture keratinocytes activation through activation of the Keap1-Nrf2-ARE pathway (Kelch-like ECH-associated protein 1)-Nrf2 (nuclear factor-erythroid 2-related factor 2)-ARE) as a response for oxidative/electrophilic stress, an important cellular defense mechanism, can be useful for predicting its potential skin sensitization properties [58,59]. Further studies show its potential application to photosafety testing assessments [60]. The h-CLAT, this time studying and measuring dendritic cell activation, is another useful method [61][62][63].…”

Section: General Requirements For the Assessment Of Toxicological Datamentioning

confidence: 99%

Safety Assessment of Nanomaterials in Cosmetics: Focus on Dermal and Hair Dyes Products

Coimbra

Sousa-Oliveira²,

Ferreira-Faria³

et al. 2022

Cosmetics

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Nanomaterials use in cosmetics is markedly enhancing, so their exposure and toxicity are important parameters to consider for their risk assessment. This review article provides an overview of the active cosmetic ingredients used for cosmetic application, including dermal cosmetics and also hair dye cosmetics, as well as their safety assessment, enriched with a compilation of the safety assessment tests available to evaluate the different types of toxicity. In fact, despite the increase in research and the number of papers published in the field of nanotechnology, the related safety assessment is still insufficient. To elucidate the possible effects that nanosized particles can have on living systems, more studies reproducing similar conditions to what happens in vivo should be conducted, particularly considering the complex interactions of the biological systems and active cosmetic ingredients to achieve newer, safer, and more efficient nanomaterials. Toward this end, ecological issues and the toxicological pattern should also be a study target.

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Development of novel in vitro photosafety assays focused on the Keap1–Nrf2–ARE pathway

Cited by 12 publications

References 39 publications

Antioxidant response elements: Discovery, classes, regulation and potential applications

Antioxidant response elements: Discovery, classes, regulation and potential applications

Development of photo‐amino acid derivative reactivity assay: a novel in chemico alternative method for predicting photoallergy

Safety Assessment of Nanomaterials in Cosmetics: Focus on Dermal and Hair Dyes Products

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