Our previous results have shown that pretreatment with the antioxidant N–tert– Butyl–􀄮–phenylnitron (PBN) improved some developmental parameters (survival, overall growth, and limb morphogenesis) in fetal rats whose mothers were treated by the epigenetic drug 5-azacytidine during the gestation. The question remained whether the PBN could improve the growth of the placenta in the same model. On the 12th and 13th days of gestation Fisher rats were pretreated by an i.v. injection of PBN (40 mg/kg) and one hour later by an i.p. injection of 5-azacytidine (5mg/kg). On the 15th and 20th days of gestation placentae were isolated. Their weight and immunohistochemically detected and stereologically quantified Proliferating Cell Nuclear Antigen (PCNA) expression was compared to sham controls, treated with PBN and/or 5-azacytidine (5-azaC) and statistically evaluated by Student’s t-test. PBN significantly improved overall growth of the placenta when applied before 5azaC. Numerical density of the PCNA signal in samples treated with 5-azaC was significantly lower than in PBN-treated or controls. Pretreatment with PBN seemed not to improve Nv for PCNA. It can be concluded that the nitrone ameliorates teratogenic impact of the epigenetic drug 5azaC upon placenta in a similar way as in fetuses meaning that this DNA demethylating agent acts, at least partially, through activation of the oxidative stress pathways.

Temeljne medicinske znanosti