A new photosafety screening strategy based on in chemico photoreactivity and in vitro skin exposure for dermally-applied chemicals

Iyama, Yosuke; Sato, Hideyuki; Seto, Yoshiki; Onoue, Satomi

doi:10.1016/j.toxlet.2019.09.016

Cited by 7 publications

(4 citation statements)

References 28 publications

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“…To improve the reliability of the photosafety testing of complex materials, as well as their photoreactivity, the pharmacokinetic behavior of major components should also be assessed with a focus on absorption, distribution to UV-exposed tissues, and skin penetration and retention. In our previous investigation, a number of potent phototoxins in humans exhibited significant permeation and accumulation in the skin, and even photoreactive chemicals with low transdermal absorbability tended to show a low phototoxic potential in animal testing (Seto et al, 2012(Seto et al, , 2020Iyama et al, 2020Iyama et al, , 2019. Thus, the combined use of the ROS assay at aMw of 250 and a pharmacokinetic study would be efficacious to make reliable photosafety predictions on the complex materials.…”

Section: Discussionmentioning

confidence: 99%

Reactive oxygen species (ROS) assay-based photosafety screening for complex ingredients: Modification of the ROS assay protocol

et al. 2022

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A reactive oxygen species (ROS) assay has been widely used for photosafety assessment; however, the phototoxic potential of complex materials, including plant extracts, essential oils, and functional polymers, is unevaluable because of their undefined molecular weights. The present study was undertaken to modify the ROS assay protocol for evaluating phototoxic potentials of those materials with use of their apparent molecular weight (aMw). On preparing sample solutions for the ROS assay, aMw ranging from 150 to 350 was tentatively employed for test substances. The modified ROS assays were applied to 45 phototoxic and 19 non-phototoxic substances, including 44 chemicals and 20 complex materials (plant extracts) for clarification of the predictive performance. Generation of ROS from photo-irradiated samples tended to increase as aMW grew, resulting in the largest number of false-positive predictions at aMW of 350. Some false-negative predictions were also observed when aMW was set at 200 or less. At aMw of 250, all tested phototoxic substances could be correctly identified as photoreactive with no false-negative predictions. Based on these observations, aMw of 250 was found to be suitable for the ROS assay on complex materials, and the sensitivity, specificity, and positive and negative predictivity for the proposed ROS assay were calculated to be 100, 52.6, 83.3, and 100%, respectively. Thus, the proposed approach may be efficacious for predicting phototoxic potentials of complex materials and contribute to the development of new products with a wide photosafety margin.

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Section: Discussionmentioning

confidence: 99%

Reactive oxygen species (ROS) assay-based photosafety screening for complex ingredients: Modification of the ROS assay protocol

et al. 2022

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“…MRT = 10 hr, (mean residence time) (Iyama, Sato, Seto, & Onoue, 2019a;Iyama, Sato, Seto, & Onoue, 2019b). XAT (IC 50 = 18 μM) showed maximum phototoxicity in Jurkat cells and…”

Section: Metabolism and Excretionmentioning

confidence: 99%

“…The latest report showed that 8‐MOP (50 μg/mL) is phytotoxin by conducting in vivo phototoxicity and by ROS analysis and PK test, and the in vivo phototoxicity results showed that T max = 4 hr, (time to maximum skin concentration); C max = 10.4 ± 1.7 (μg/g skin); MRT = 10 hr, (mean residence time) (Iyama, Sato, Seto, & Onoue, 2019a; Iyama, Sato, Seto, & Onoue, 2019b). XAT (IC 50 = 18 μM) showed maximum phototoxicity in Jurkat cells and HaCaT cells (Schempp, Simon‐Haarhaus, Krieger, & Simon, 2006).…”

Section: Toxicitymentioning

confidence: 99%

Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

Zhong

et al. 2022

Phytotherapy Research

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Xanthotoxin (XAT) is a natural furanocoumarins, a bioactive psoralen isolated from the fruit of the Rutaceae plant Pepper, which has received increasing attention in recent years due to its wide source and low cost. By collecting and compiling literature on XAT, the results show that XAT exhibits significant activity in the treatment of various diseases, including neuroprotection, skin repair, osteoprotection, organ protection, anticancer, antiinflammatory, antioxidative stress and antibacterial. In this paper, we review the pharmacological activity and potential molecular mechanisms of XAT for the treatment of related diseases. The data suggest that XAT can mechanistically induce ROS production and promote apoptosis through mitochondrial or endoplasmic reticulum pathways, regulate NF‐κB, MAPK, JAK/STAT, Nrf2/HO‐1, MAPK, AKT/mTOR, and ERK1/2 signaling pathways to exert pharmacological effects. In addition, the pharmacokinetics properties and toxicity of XAT are discussed in this paper, further elucidating the relationship between structure and efficacy. It is worth noting that data from clinical studies of XAT are still scarce, limiting the use of XAT in the clinic, and in the future, more in‐depth studies are needed to determine the clinical efficacy of XAT.

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“…The results proved the potency of this method to explore the skin sensitization potential of carbonyl-containing Michael acceptor chemicals. 158 For skin photoreactivity, except in vivo or in vitro experimental detection techniques, such as Photopatch test and UV absorption, 159 several feature-based rules were developed for screening. Peukert et al found that a compound that owns a HOMO−LUMO gap between 6.7 and 8.1 eV and has an association with molar absorptivity values above 2500 M −1 cm −1 will have a high risk of photoreactivity.…”

Section: ■ Adverse Skin Reactionmentioning

confidence: 99%

Application of Negative Design To Design a More Desirable Virtual Screening Library

Yang

Lü

et al. 2020

J. Med. Chem.

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Negative design is a group of virtual screening methods that aims at weeding out compounds with undesired properties during the early stages of drug development. These methods are mainly designed to predict three important types of pharmacological properties: drug-likeness, frequent hitters, and toxicity. In order to achieve high screening efficiency, most negative design methods are physicochemical property-based and/or substructure-based rules or filters. Such methods have advantages of simplicity and good interpretability, but they also suffer from some defects such as inflexibility, discontinuity, and hard decisionmaking. In this review, the advances in negative design for the evaluations of druglikeness, frequent hitters, and toxicity are outlined. In addition, the related Web servers and software packages developed recently for negative design are summarized. Finally, future research directions in this field are discussed.

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A new photosafety screening strategy based on in chemico photoreactivity and in vitro skin exposure for dermally-applied chemicals

Cited by 7 publications

References 28 publications

Reactive oxygen species (ROS) assay-based photosafety screening for complex ingredients: Modification of the ROS assay protocol

Reactive oxygen species (ROS) assay-based photosafety screening for complex ingredients: Modification of the ROS assay protocol

Xanthotoxin (8‐methoxypsoralen): A review of its chemistry, pharmacology, pharmacokinetics, and toxicity

Application of Negative Design To Design a More Desirable Virtual Screening Library

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