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Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage

Excessive UV-B exposure is well known to be a risk factor for corneal phototoxicity including direct DNA damage and disturbances in the antioxidant balance. Here, we showed a successful synthesis of a water-soluble and biocompatible small molecule DHPM 1 with dihydropyrimidinthione skeleton, which c...

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Autores principales: Du, Enming, Pu, Guojuan, He, Siyu, Qin, Fangyuan, Wang, Yange, Wang, Gang, Song, Zongming, Zhang, Junjie, Tao, Ye
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570246/
https://www.ncbi.nlm.nih.gov/pubmed/34744716
http://dx.doi.org/10.3389/fphar.2021.732833
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author Du, Enming
Pu, Guojuan
He, Siyu
Qin, Fangyuan
Wang, Yange
Wang, Gang
Song, Zongming
Zhang, Junjie
Tao, Ye
author_facet Du, Enming
Pu, Guojuan
He, Siyu
Qin, Fangyuan
Wang, Yange
Wang, Gang
Song, Zongming
Zhang, Junjie
Tao, Ye
author_sort Du, Enming
collection PubMed
description Excessive UV-B exposure is well known to be a risk factor for corneal phototoxicity including direct DNA damage and disturbances in the antioxidant balance. Here, we showed a successful synthesis of a water-soluble and biocompatible small molecule DHPM 1 with dihydropyrimidinthione skeleton, which could effectively protect human corneal epithelial (HCE-2) cells from UV-B damage. In separate experiments, DHPM 1 absorbed UV-B rays and exhibited scavenging activity against intracellular ROS induced by UV-B radiation, thereby reducing the levels of DNA fragmentation. Additionally, UV-B exposure increased the expression of cleaved caspase-3, as well as the ratio of Bax/Bcl-2 at protein levels, while pretreatment with DHPM 1 significantly reversed these changes. To the best of our knowledge, this is the first report of a study based on dihydropyrimidinthione derivatives to develop a promising eye drops, which may well find extensive applications in UV-B caused corneal damage.
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spelling pubmed-85702462021-11-06 Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage Du, Enming Pu, Guojuan He, Siyu Qin, Fangyuan Wang, Yange Wang, Gang Song, Zongming Zhang, Junjie Tao, Ye Front Pharmacol Pharmacology Excessive UV-B exposure is well known to be a risk factor for corneal phototoxicity including direct DNA damage and disturbances in the antioxidant balance. Here, we showed a successful synthesis of a water-soluble and biocompatible small molecule DHPM 1 with dihydropyrimidinthione skeleton, which could effectively protect human corneal epithelial (HCE-2) cells from UV-B damage. In separate experiments, DHPM 1 absorbed UV-B rays and exhibited scavenging activity against intracellular ROS induced by UV-B radiation, thereby reducing the levels of DNA fragmentation. Additionally, UV-B exposure increased the expression of cleaved caspase-3, as well as the ratio of Bax/Bcl-2 at protein levels, while pretreatment with DHPM 1 significantly reversed these changes. To the best of our knowledge, this is the first report of a study based on dihydropyrimidinthione derivatives to develop a promising eye drops, which may well find extensive applications in UV-B caused corneal damage. Frontiers Media S.A. 2021-10-20 /pmc/articles/PMC8570246/ /pubmed/34744716 http://dx.doi.org/10.3389/fphar.2021.732833 Text en Copyright © 2021 Du, Pu, He, Qin, Wang, Wang, Song, Zhang and Tao. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Du, Enming
Pu, Guojuan
He, Siyu
Qin, Fangyuan
Wang, Yange
Wang, Gang
Song, Zongming
Zhang, Junjie
Tao, Ye
Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
title Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
title_full Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
title_fullStr Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
title_full_unstemmed Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
title_short Cytoprotective Effects of Water Soluble Dihydropyrimidinthione Derivative Against UV-B Induced Human Corneal Epithelial Cell Photodamage
title_sort cytoprotective effects of water soluble dihydropyrimidinthione derivative against uv-b induced human corneal epithelial cell photodamage
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8570246/
https://www.ncbi.nlm.nih.gov/pubmed/34744716
http://dx.doi.org/10.3389/fphar.2021.732833
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