Apocynin inhibits placental TLR4/NF-κB signaling pathway and ameliorates preeclampsia-like symptoms in rats

Objective: We aimed to investigate the potency of apocynin in ameliorating preeclampsia and explore the underlying mechanisms. Methods: Preeclampsia model was constructed in rats by administering 200 mg/kg/day L-NAME. Apocynin was given orally in drinking water. Systolic blood pressure and proteinuria were monitored during treatment. Survival rate rate of the pups and placental weight were assessed. Serum sFlt-1, PIGF, IL-6 and placental TLR4 levels were measured using ELISA or qRT-PCR. Results: Apocynin dose-dependently decreased systolic blood pressure and proteinuria during gestation. Survival rate of the pups and placental weight were improved by apocynin treatment. Apocynin ameliorated the imbalance of sFlt-1 and PIGF in serum and placenta of rats with preeclampsia. Apocynin attenuated serum inflammatory cytokine expression and placental inflammation most likely due to downregulation of the placental TLR4/NF-kB pathway in L-NAME treated rats. Conclusions: Apocynin potently ameliorates the L-NAME-induced preeclampsia, which is achieved by rebalancing the sFlt-1 and PIGF levels, attenuating inflammation, and inhibiting TLR4/NF-kappa B p65 signaling.