Extended Prophylactic Effect of N-tert-Butyl-α-phenylnitron against Oxidative/Nitrosative Damage Caused by the DNA-Hypomethylating Drug 5-Azacytidine in the Rat Placenta
العنوان: | Extended Prophylactic Effect of N-tert-Butyl-α-phenylnitron against Oxidative/Nitrosative Damage Caused by the DNA-Hypomethylating Drug 5-Azacytidine in the Rat Placenta |
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المؤلفون: | Nikola Sobočan, Marta Himelreich-Perić, Ana Katušić-Bojanac, Jure Krasić, Nino Sinčić, Željka Majić, Gordana Jurić-Lekić, Ljiljana Šerman, Andreja Marić, Davor Ježek, Floriana Bulić-Jakuš |
المصدر: | International Journal of Molecular Sciences; Volume 23; Issue 2; Pages: 603 International Journal of Molecular Sciences, Vol 23, Iss 603, p 603 (2022) International Journal of Molecular Sciences |
بيانات النشر: | Multidisciplinary Digital Publishing Institute, 2022. |
سنة النشر: | 2022 |
مصطلحات موضوعية: | Proliferating Cell Nuclear Antigen / metabolism, Placenta / drug effects, 5-azacytidine, N-tert-Butyl-α-phenylnitron, PBN, placenta, oxoguanosine, nitrotyrosine, oxidative stress, Cyclic N-Oxides / pharmacology, Nitrosation / drug effects, Biomarkers / metabolism, Pregnancy, Biology (General), DNA Methylation / drug effects, Spectroscopy, reproductive and urinary physiology, Tyrosine / metabolism, General Medicine, Organ Size, Computer Science Applications, Oxidative Stress / drug effects, Chemistry, 8-Hydroxy-2'-Deoxyguanosine, embryonic structures, Azacitidine, 8-Hydroxy-2'-Deoxyguanosine / metabolism, Female, QH301-705.5, Nitrosation, Catalysis, Article, Inorganic Chemistry, Cyclic N-Oxides, Proliferating Cell Nuclear Antigen, Placenta / pathology, Animals, Physical and Theoretical Chemistry, Molecular Biology, QD1-999, Cell Proliferation, Tyrosine / analogs & derivatives, Organic Chemistry, DNA Methylation, Rats, Inbred F344, Organ Size / drug effects, Oxidative Stress, Tyrosine, Cell Proliferation / drug effects, Azacitidine / toxicity, Biomarkers |
الوصف: | Antioxidant N-tert-Butyl-α-phenylnitron (PBN) partly protected embryos from the negative effects of a DNA demethylating drug 5-azacytidine during pregnancy. Our aim was to investigate PBN’s impact on the placenta. Fischer rat dams were treated on gestation days (GD) 12 and 13 by PBN (40 mg/kg), followed by 5azaC (5 mg/kg) after one hour. Global methylation was assessed by pyrosequencing. Numerical density was calculated from immunohistochemical expression in single cells for proliferating (PCNA), oxidative (oxoguanosine) and nitrosative (nitrotyrosine) activity. Results were compared with the PBN-treated and control rats. PBN-pretreatment significantly increased placental weight at GD15 and GD20, diminished by 5azaC, and diminished apoptosis in GD 20 placentas caused by 5azaC. Oxoguanosine expression in placentas of 5azaC-treated dams was especially high in the placental labyrinth on GD 15, while PBN-pretreatment lowered its expression on GD 15 and GD 20 in both the labyrinth and basal layer. 5azaC enhanced nitrotyrosine level in the labyrinth of both gestational stages, while PBN-pretreatment lowered it. We conclude that PBN exerted its prophylactic activity against DNA hypomethylating agent 5azaC in the placenta through free radical scavenging, especially in the labyrinthine part of the placenta until the last day of pregnancy. |
وصف الملف: | application/pdf |
اللغة: | English |
تدمد: | 1422-0067 |
DOI: | 10.3390/ijms23020603 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2fdb5992b1798da16989b4cf40783133 |
Rights: | OPEN |
رقم الانضمام: | edsair.doi.dedup.....2fdb5992b1798da16989b4cf40783133 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 14220067 |
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DOI: | 10.3390/ijms23020603 |