The role of ferritin and iron dextran in exacerbating preeclampsia in an L-NAME-treated rat model.

Background: Preeclampsia (PE) occurs in the second half of pregnancy and contributes to maternal and perinatal morbidity and mortality. Ferritin plays a key role in pregnancy, but the underlying mechanisms of its involvement in PE remain elusive. This study aimed to investigate the effects of ferritin concentrations and ferroptosis levels on PE rats at different stages of pregnancy. Methods: A PE rat model was established by administering nitro-L-arginine methyl ester (L-NAME; 60 mg/kg/day, orally) between the 13th and 19th days of pregnancy. Iron dextran (ID) was used to induce ferroptosis, whereas deferoxamine (DFO) was used to prevent ferroptosis. Pathological changes in the placenta and vascular system were observed by hematoxylin and eosin (H&E) staining. Oxidative stress levels, blood pressure, and urine protein levels were assessed. Inflammatory cytokines and cellular ferritin (FER)-related proteins were measured by enzyme-linked immunosorbent assay (ELISA). Western blot was performed to assess apoptosis- and ferroptosis-related proteins. Results: The data showed that L-NAME elevated blood pressure and urine protein levels in pregnant rats, while treatment with DFO-late and ID-early reduced them. Placental and vascular damage were ameliorated, and the levels of nitric oxide (NO), nitric oxide synthase (NOS), and superoxide dismutase (SOD) were increased. In contrast, the generation of reactive oxygen species (ROS), malonaldehyde (MDA), inflammatory factors, and FER-related proteins were suppressed, accompanied by reduced apoptosis- and increased ferroptosis-related proteins in the DFO-late group. Conclusions: Our results suggested that decreased ferritin levels in early pregnancy or elevated ferritin levels in late pregnancy in an L-NAME-treated rat model accelerated ferroptosis and exacerbated PE symptoms.