Supplementation with dietary omega-3 PUFA mitigates fetal brain inflammation and mitochondrial damage caused by high doses of sodium nitrite in maternal rats

OBJECTIVE: Food safety and nutrition during pregnancy are important concerns related to fetal brain development. In the present study, we aimed to explore the effects of omega-3 polyunsaturated fatty acids (PUFA ω-3) on exogenous sodium nitrite intervention-induced fetal brain injury in pregnant rats. METHODS: During pregnancy, rats were exposed to water containing sodium nitrite (0.05%, 0.15%, and 0.25%) to establish a fetal rat brain injury model. Inflammatory factors and oxidative stress levels were detected using enzyme-linked immunosorbent assay (ELISA) or flow cytometry. Subsequently, animals were divided into three groups: control, model, and 4% PUFA ω-3. Pregnancy outcomes were measured and recorded. Hematoxylin-eosin (H&E) staining and immunohistochemistry (IHC) were utilized to observe brain injury. ELISA, quantitative real-time PCR (qRT-PCR), western blot, flow cytometry, and transmission electron microscopy (TEM) were adopted to measure the levels of inflammatory factors, the NRF1/HMOX1 signaling pathway, and mitochondrial and oxidative stress damage. RESULTS: With the increase of sodium nitrite concentration, the inflammatory factors and oxidative stress levels increased. Therefore, the high dose group was set as the model group for the following experiments. After PUFA ω-3 treatment, the fetal survival ratio, average body weight, and brain weight were elevated. The cells in the PUFA ω-3 group were more closely arranged and more round than the model. PUFA ω-3 treatment relieved inflammatory factors, oxidative stress levels, and mitochondria damage while increasing the indicators related to brain injury and NRF1/HMOX1 levels. CONCLUSIONS: Sodium nitrite exposure during pregnancy could cause brain damage in fetal rats. PUFA ω-3 might help alleviate brain inflammation, oxidative stress, and mitochondrial damage, possibly through the NRF1/HMOX1 signaling pathway. In conclusion, appropriately reducing sodium nitrite exposure and increasing PUFA omega-3 intake during pregnancy may benefit fetal brain development. These findings could further our understanding of nutrition and health during pregnancy.