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

Znanstveni rad - Izvorni znanstveni rad

• Autor: Nikola Sobočan
• Autor: Marta Himelreich-Perić
• Autor: Ana Katušić-Bojanac
• Autor: Jure Krasić
• Autor: Nino Sinčić
• Autor: Željka Majić
• Autor: Gordana Jurić-Lekić
• Autor: Ljiljana Šerman
• Autor: Andreja Marić
• Autor: Davor Ježek
• Autor: Floriana Bulić-Jakuš
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA HISTOLOGIJU I EMBRIOLOGIJU)
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA MEDICINSKU BIOLOGIJU)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Temeljne medicinske znanosti; Citologija, histologija i embriologija

Sažetak (engleski)

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.

• Ključne riječi (engleski): 8-Hydroxy-2'-Deoxyguanosine / metabolism; Animals; Azacitidine / toxicity; Biomarkers / metabolism; Cell Proliferation / drug effects; Cyclic N-Oxides / pharmacology; DNA Methylation / drug effects; Female; Nitrosation / drug effects; Organ Size / drug effects; Oxidative Stress / drug effects; Placenta / drug effects; Placenta / pathology; Pregnancy; Proliferating Cell Nuclear Antigen / metabolism; Rats, Inbred F344; Tyrosine / analogs & derivatives; Tyrosine / metabolism
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: International Journal of Molecular Sciences
• Brojčani podaci: vol. 23, br. 2, 603
• e-ISSN: 1422-0067
• DOI: https://doi.org/10.3390/ijms23020603
• URN:NBN: urn:nbn:hr:105:168102
• Datum objave publikacije: 2022-01-06
• Projekt: Šifra: KK.01.1.1.01.0008; Naziv (hrvatski): Reproduktivna i regenerativna medicina - istraživanje novih platformi i potencijala; Voditelj: Ana Katušić Bojanac; Pravna nadležnost: eu; Financijer: MZO
• Projekt: Šifra: 108-1080399-0335; Naziv (hrvatski): Eksperimentalni embrionalni tumori i razvoj zametaka sisavaca in vitro i in vivo; Naziv (engleski): Experimental embryonic tumors and mammalian development in vitro and in vivo; Voditelj: Florijana Jakuš; Pravna nadležnost: Hrvatska; Financijer: MZOS; Linija financiranja: ZP
• URL dokumenta: https://www.mdpi.com/1422-0067/23/2/603
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2022-11-15 09:31:55