Cause Clarification of Cysteine Oxidation by Active Species Generated during the Oxidation Process of Cinnamaldehyde and Impact on an In Chemico Alternative Method for Skin Sensitization Using a Nucleophilic Reagent Containing Cysteine,Chemical Research in Toxicology

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Cause Clarification of Cysteine Oxidation by Active Species Generated during the Oxidation Process of Cinnamaldehyde and Impact on an In Chemico Alternative Method for Skin Sensitization Using a Nucleophilic Reagent Containing Cysteine
Chemical Research in Toxicology ( IF 3.7 ) Pub Date : 2021-06-10 , DOI: 10.1021/acs.chemrestox.1c00097
Masaharu Fujita ₁ , Yusuke Yamamoto ₁ , Kumiko Watanabe ₂ , Koo Suzuki ₂ , Toshihiko Kasahara ₁

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Aldehydes comprise a major portion of skin sensitizers because they can react with both cysteine and lysine. Moreover, cinnamaldehyde (CA) is a typical moderate sensitizer and is often used in an alternative test method for skin sensitization. The amino acid derivative reactivity assay (ADRA) is an in chemico test method that evaluates the reactivity of cysteine derivatives (N-(2-(1-naphthyl)acetyl)-l-cysteine, NAC) and lysine derivatives with the test chemicals and uses CA as a proficiency substance. We found that NAC depletion for CA was only 10–20% when CA was used directly from the reagent bottle, although it increased to almost 100% when stored after being aliquoted from the reagent bottle. It was also found that this was due to the air oxidation of NAC itself rather than the reaction of NAC with CA, indicating that this result simply shows an increase in apparent reactivity. Aldehydes are known to produce active species, such as radicals, during air oxidation. Therefore, we investigated whether radicals were generated under storage conditions using the radical scavenger OH-TEMPO. LC/MS/MS analysis revealed that CA and OH-TEMPO complexes were produced during the air oxidation of CA. In the results of five aldehydes, similar to CA, active species were not generated as significantly as CA. Collectively, during the evaluation of the aldehydes, it can be seen that careful measures need to be taken to prevent the aldehydes from oxidizing during storage, indicating that assessment without preventing air oxidation carries an increased risk of overestimation compared with the intrinsic skin sensitization potency.

中文翻译：

肉桂醛氧化过程中产生的活性物质对半胱氨酸氧化的原因澄清以及对使用含有半胱氨酸的亲核试剂引起皮肤过敏的化学替代方法的影响

醛类构成皮肤致敏物的主要部分，因为它们可以与半胱氨酸和赖氨酸发生反应。此外，肉桂醛 (CA) 是一种典型的中度致敏剂，通常用于皮肤致敏的替代测试方法。氨基酸衍生物反应性测定 (ADRA) 是一种化学测试方法，用于评估半胱氨酸衍生物 ( N -(2-(1-萘基)乙酰)- l-半胱氨酸，NAC）和赖氨酸衍生物与测试化学品，并使用 CA 作为熟练物质。我们发现当 CA 直接从试剂瓶中使用时，CA 的 NAC 消耗仅为 10-20%，尽管从试剂瓶中等分后储存时，它增加到几乎 100%。还发现这是由于 NAC 本身的空气氧化而不是 NAC 与 CA 的反应，表明该结果仅显示表观反应性的增加。已知醛在空气氧化过程中会产生活性物质，例如自由基。因此，我们使用自由基清除剂 OH-TEMPO 研究了在储存条件下是否会产生自由基。LC/MS/MS 分析表明 CA 和 OH-TEMPO 复合物是在 CA 的空气氧化过程中产生的。在五种醛的结果中，与 CA 相似，活性物种的产生不如 CA。总的来说，在对醛的评估过程中，可以看出需要采取谨慎的措施来防止醛在储存过程中氧化，这表明与固有的皮肤致敏效力相比，在不防止空气氧化的情况下进行评估会增加高估的风险。

更新日期：2021-07-19

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