{"title":"Melatonin mitigates UV-induced tumorigenesis and suppresses hearing function deterioration in Xpa-deficient mice","authors":"Mariko Tsujimoto , Takeshi Fujita , Tatsuya Furukawa , Yaeno Arima , Ken-Ichi Nibu , Chikako Nishigori","doi":"10.1016/j.jdermsci.2025.01.003","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Objective</h3><div>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.</div></div><div><h3>Methods</h3><div>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 <em>Xpa</em>-deficient MEF on UV-induced cytotoxicity and ROS production, and for <em>Xpa-</em>deficient mice on UV-induced skin tumorigenesis and auditory brainstem responses as one of the neurological symptoms.</div></div><div><h3>Results</h3><div>Melatonin and nicotinamide attenuated 4NQO-induced oxidative cytotoxicity. UV-induced intracellular ROS production and cytotoxicity were improved by melatonin for <em>Xpa</em>-deficient MEF. Finally, the administration of melatonin mitigated UV-induced skin inflammation and tumorigenesis and suppressed hearing deterioration in <em>Xpa</em>-deficient mice.</div></div><div><h3>Conclusion</h3><div>Our results show that melatonin could alleviate XP symptoms through its anti-inflammatory and antioxidant properties.</div></div>","PeriodicalId":94076,"journal":{"name":"Journal of dermatological science","volume":"117 3","pages":"Pages 81-87"},"PeriodicalIF":4.6000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of dermatological science","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0923181125000039","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
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.