Redox-driven disruption of nitric oxide-dependent angiogenic and inflammatory signaling in cadmium-exposed rat placenta: modulation by dietary soy.

Placental Cd accumulation was associated with altered Zn, Fe, and Cu homeostasis and increased lipid peroxidation, indicating redox imbalance. Cd exposure upregulated metallothionein II expression and altered the gene expression of the redox-sensitive markers Nrf2, FOXO3, and HO-1, consistent with modulation of stress-responsive gene expression. Gene expression of stress-responsive and vascular markers was evaluated by semi-quantitative RT-PCR. Concomitantly, VEGF and eNOS expression were increased, suggesting redox-sensitive changes in angiogenic and vasoactive gene expression under Cd exposure, while IL-6 elevation indicated a pro-inflammatory environment. Notably, the soy-based diet differentially modulated these responses, being associated with higher GPx activity, and lower IL-6 expression. Histological and immunohistochemical analyses confirmed structural alterations and dysregulation of the apoptosis-proliferation balance in placental tissue. Collectively, these findings indicate that Cd-induced placental dysfunction involves redox-associated changes in the expression of NO-dependent angiogenic and inflammatory mediators, and that dietary soy partially shifts this response toward improved redox balance and vascular response.