Evaluation of colostrum-coated ZnO nanoparticles (C-ZnONPs) in attenuating valproic acid-induced prenatal toxicity.

Valproic acid (VPA) is a broad-spectrum antiepileptic and mood-stabilizing drug, but its use during pregnancy is associated with oxidative stress-mediated teratogenicity and neurodevelopmental impairments. Given that discontinuation of VPA therapy is often not feasible in women with refractory epilepsy or severe mood disorders, development of effective adjunctive protective strategies is critical. Our previous work on "Eco-Friendly ZnO Nanoparticle Synthesis and Colostrum Coating" demonstrated that C-ZnONPs exhibit superior antioxidant stability and biocompatibility. Building on this, the present study examined their protective efficacy against VPA-induced developmental toxicity. Pregnant albino mice (n = 20) were assigned to four groups: control, VPA (500 mg/kg), VPA + C-ZnONPs (30 mg/kg), and VPA + C-ZnONPs (50 mg/kg), treated from gestational day (GD) 5-15. On GD19, oxidative stress biomarkers, reproductive indices, fetal growth parameters, and morphological anomalies were evaluated. VPA exposure caused pronounced oxidative stress, elevating CAT, MDA, nitrite, and GSH while suppressing SOD activity. Reproductive toxicity was evident through increased resorptions (early 2.9; late 4.1), abortions (0.8), decreased fetal weight (1.02 g), and reduced crown-rump length (0.92 cm), along with hepatic injury and multiple fetal malformations. Co-administration of C-ZnONPs produced dose-dependent protection: 30 mg/kg partially normalized oxidative markers and growth, whereas 50 mg/kg restored antioxidant balance, markedly reduced resorption, and improved fetal development. Both doses reduced morphological deformities, though not linearly. Collectively, these findings suggest that C-ZnONPs may attenuate VPA-induced oxidative stress and developmental abnormalities, although further mechanistic and translational studies are required to establish their therapeutic potential.