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A free radical scavenger ameliorates teratogenic activity of a DNA hypomethylating hematological therapeutic (CROSBI ID 284865)

Prilog u časopisu | izvorni znanstveni rad | međunarodna recenzija

Sobočan, Nikola ; Katušić Bojanac, Ana ; Sinčić, Nino ; Himelreich-Perić, Marta ; Krasić, Jure ; Majić, Željka ; Jurić-Lekić, Gordana ; Šerman, Ljiljana ; Vlahović, Maja ; Ježek, Davor et al. A free radical scavenger ameliorates teratogenic activity of a DNA hypomethylating hematological therapeutic // Stem cells and development, 28 (2019), 11; 717-733. doi: 10.1089/scd.2018.0194

Podaci o odgovornosti

Sobočan, Nikola ; Katušić Bojanac, Ana ; Sinčić, Nino ; Himelreich-Perić, Marta ; Krasić, Jure ; Majić, Željka ; Jurić-Lekić, Gordana ; Šerman, Ljiljana ; Vlahović, Maja ; Ježek, Davor ; Bulić- Jakuš, Floriana

engleski

A free radical scavenger ameliorates teratogenic activity of a DNA hypomethylating hematological therapeutic

The spin-trap free radical scavenger N-tert-butyl- a-phenylnitron (PBN) ameliorated effects of several teratogens involving reactive oxygen species (ROS). We investigated for the first time whether PBN could ameliorate teratogenesis induced by a DNA hypomethylating hematological therapeutic 5-azacytidine (5azaC). At days 12 and 13 of gestation, Fisher rat dams were pretreated by an i.v. injection of PBN (40mg/kg) and 1 h later by an i.p. injection of 5azaC (5mg/kg). Development was analyzed at gestation day 15 in embryos and day 20 in fetuses. PBN alone did not significantly affect development. PBN pretreatment restored survival of 5azaC-treated dams’ embryos to the control level, restored weight of embryos and partially of fetuses, and partially restored crownrump lengths. PBN pretreatment converted limb adactyly to less severe oligodactyly. PBN pretreatment restored global DNA methylation level in the limb buds to the control level. Cell proliferation in limb buds of all 5azaCtreated dams remained significantly lower than in controls. In the embryonic liver, PBN pretreatment normalized proliferation diminished significantly by 5azaC ; whereas in embryonic vertebral cartilage, proliferation of all 5azaC-treated dams was significantly higher than in PBN-treated dams or controls. Apoptotic indices significantly enhanced by 5azaC in liver and cartilage were not influenced by PBN pretreatment. However, PBN significantly diminished ROS or reactive nitrogen species markers nitrotyrosine and 8-hydroxy- 2¢deoxyguanosine elevated by 5azaC in embryonic tissues, and, therefore, activity of this DNA hypomethylating agent was associated to the activation of free radicals. That pretreatment with PBN enhanced proliferation in the liver and not in immature tissue is interesting for the treatment of 5azaC-induced hepatotoxicity and liver regeneration.

5-azacytidine ; N-tert–butyl-a-phenylnitron ; embryo ; teratogenesis ; ROS/RNS

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Podaci o izdanju

28 (11)

2019.

717-733

objavljeno

1547-3287

1557-8534

10.1089/scd.2018.0194

Povezanost rada

Temeljne medicinske znanosti

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