Nicotinamide ameliorate ADMA-induced fetal growth restriction in mice via reducing oxidative stress levels

doi:10.3969/j.issn.1006-7795.2025.06.017

Abstract

Abstract: Objective To elucidate the role of asymmetric dimethylarginine (ADMA) on fetal growth restriction (FGR) induced by oxidative stress in vivo experiments in mice, and to explore the protective effect of nicotinamide (NAM) on FGR and its mechanism. Methods The FGR mouse model was established by injecting ADMA on the nape of the neck, and the experiment was divided into the control group, ADMA group, NAM group, and ADMA + NAM group. The successful construction of the FGR mouse model was evaluated by detecting the weight of fetal mice. The placental tissues were stained with hematoxylin-eosin (HE) and the morphological changes of villi and interstitium were observed. The levels of ADMA in placenta and serum were detected by enzyme-linked immunosorbent assay (ELISA). Biochemical tests were used to detect the levels of malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), and total glutathione (T-GSH) in placenta. Additionally, the level of reactive oxygen species (ROS) in placenta was quantitatively analyzed by fluorescence. The expression levels of superoxide dismutase 1 (SOD1) and anti-apoptotic protein B-cell lymphoma-2 (Bcl-2) in placenta were detected by Western blotting (WB) experiments. Results In comparison to the control, NAM, and ADMA+NAM group, the incidence of FGR in the ADMA group was significantly increased, and placental dysplasia was observed. Moreover, the ADMA group displayed significantly higher levels of MDA and ROS, and lower levels of GSH/GSSG of the placenta in mice, in contrast to the control group. Additionally, the expression levels of SOD1 and Bcl-2 proteins in the ADMA group decreased, when compared to the control group. NAM can significantly improve placental developmental disorders and FGR induced by ADMA through reducing oxidative stress levels. Conclusion The application of an appropriate dose of NAM in early pregnancy could alleviate ADMA-induced placental dysfunction and FGR by improving oxidative damage.

Key words: fetal growth restriction, asymmetric dimethylarginine, oxidative stress, nicotinamide, mouse model, apoptosis

CLC Number:

R714.2

Dai Yan, Sang Xiubo, Bai Wenpei, Zhang Jin. Nicotinamide ameliorate ADMA-induced fetal growth restriction in mice via reducing oxidative stress levels[J]. Journal of Capital Medical University, doi: 10.3969/j.issn.1006-7795.2025.06.017.

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