Perinatal nicotine-induced neurotoxicity and behavioral alterations in newborn mice are associated with oxidative stress, inflammation and downregulated Nrf2/HO-1 signaling: protective role of Anethum graveolens.

Perinatal exposure to nicotine has been implicated in causing significant oxidative stress and long-term neurobehavioral abnormalities. This study explores, for the first time, the efficacy of Anethum graveolens (dill) extract in mitigating neurotoxicity, oxidative damage, inflammation, and behavioral disturbances in neonatal mice exposed to nicotine during the perinatal period. Pregnant mice were administered 50 mg/kg of A. graveolens extract orally from gestational day 1 (GD1) to postnatal day 15 (PD15), alongside subcutaneous injections of nicotine (0.25 mg/kg) from GD12 to PD15. Nicotine-exposed neonates exhibited delayed developmental milestones (eye opening and hair growth), impaired neuromotor functions (righting, rotating, and cliff avoidance reflexes), and heightened anxiety-like behaviors. Nicotine induced substantial tissue damage, elevated levels of reactive oxygen species (ROS), malondialdehyde (MDA), and pro-inflammatory cytokines, and suppressed glutathione (GSH) levels and antioxidant enzyme activities across different brain regions (cerebrum, cerebellum, and medulla oblongata). A. graveolens extract improved developmental markers, restored neuromotor functions, reduced anxiety-like behaviors, and attenuated oxidative stress and inflammation. Moreover, it enhanced antioxidant defenses and upregulated the expression of Nrf2 and heme oxygenase-1 (HO-1). These findings indicate that A. graveolens exerts a protective role against nicotine-induced neurotoxicity by modulating oxidative and inflammatory responses and attenuating neurobehavioral alterations.