Melatonin mitigates UV-induced tumorigenesis and suppresses hearing function deterioration in Xpa-deficient mice

IF 4.6

Journal of dermatological science Pub Date : 2025-03-01 DOI:10.1016/j.jdermsci.2025.01.003

Mariko Tsujimoto , Takeshi Fujita , Tatsuya Furukawa , Yaeno Arima , Ken-Ichi Nibu , Chikako Nishigori

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引用次数: 0

Abstract

Background

Xeroderma pigmentosum (XP) is caused by impaired DNA repair of UV-induced dipyrimidine-photoproducts. XP cells also show impaired repair/removal of ROS or oxidative DNA lesions caused by UV or 4-nitroquinolline 1-oxide (4NQO). Gene profiling indicated that inflammatory response-related genes are significantly upregulated after UV exposure in XP-A model mice.

Objective

Since XP cells are in the state of oxidative stress and inflammation, we aimed to search for therapeutic agents from anti-oxidants/anti-inflammatory drugs, that potentially improve XP symptoms.

Methods

Several antioxidants were examined for reducing 4NQO-induced oxidative cytotoxicity or UV-induced oxidative DNA damage in XP-A cells. Among them, we focused on melatonin and evaluated its improving effect for Xpa-deficient MEF on UV-induced cytotoxicity and ROS production, and for Xpa-deficient mice on UV-induced skin tumorigenesis and auditory brainstem responses as one of the neurological symptoms.

Results

Melatonin and nicotinamide attenuated 4NQO-induced oxidative cytotoxicity. UV-induced intracellular ROS production and cytotoxicity were improved by melatonin for Xpa-deficient MEF. Finally, the administration of melatonin mitigated UV-induced skin inflammation and tumorigenesis and suppressed hearing deterioration in Xpa-deficient mice.

Conclusion

Our results show that melatonin could alleviate XP symptoms through its anti-inflammatory and antioxidant properties.

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褪黑素减轻紫外线诱导的肿瘤发生，抑制xpa缺陷小鼠的听力功能恶化。

背景：色素性干皮病（XP）是由紫外线诱导的双嘧啶光产物DNA修复受损引起的。XP细胞还表现出由紫外线或4-硝基喹啉1-氧化物（4NQO）引起的ROS或氧化性DNA损伤的修复/去除受损。基因谱分析表明，XP-A模型小鼠在紫外线照射后炎症反应相关基因显著上调。目的：由于XP细胞处于氧化应激和炎症状态，我们旨在从抗氧化剂/抗炎药物中寻找可能改善XP症状的治疗剂。方法：研究几种抗氧化剂对4nqo诱导的XP-A细胞氧化毒性或紫外线诱导的DNA氧化损伤的影响。其中，我们重点研究了褪黑激素，并评估了褪黑激素对xpa缺陷MEF对紫外线诱导的细胞毒性和ROS产生的改善作用，以及作为神经系统症状之一的xpa缺陷小鼠对紫外线诱导的皮肤肿瘤发生和听觉脑干反应的改善作用。结果：褪黑素和烟酰胺可减弱4nqo诱导的氧化细胞毒性。褪黑素可改善xpa缺乏MEF的细胞内ROS生成和细胞毒性。最后，给药褪黑素减轻紫外线诱导的皮肤炎症和肿瘤发生，并抑制xpa缺陷小鼠的听力退化。结论：褪黑素可通过其抗炎、抗氧化作用缓解XP症状。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of dermatological science Dermatology

CiteScore

7.60

自引率

0.00%

发文量