Lutein-loaded nanoparticles reverse oxidative stress, apoptosis, and autism spectrum disorder-like behaviors induced by prenatal valproic acid exposure in female rats

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social interaction and repetitive behaviors. In this study, we assessed the effect of lutein-loaded nanoparticles on ASD-like behaviors induced by prenatal valproic acid (VPA) exposure in female offspring rats and the possible involvement of oxidative stress and apoptosis. Pregnant female Wistar rats received a single intraperitoneal injection of VPA (600 mg/kg), on the gestational day 12.5. The VPA-exposed female offspring rats were divided into two subgroups and received either lutein-loaded nanoparticles (5 mg/kg) or saline by oral gavage, for 14 days. The animals were submitted to the three-chamber test and open field to evaluate ASD-like behaviors. The hippocampus was removed for the determination of oxidative stress indicators (ROS; TBARS; SOD and Nrf2) and apoptosis biomarkers (Hsp-70; p38-MAPK; Bax and Bcl-2). The exposure to lutein-loaded nanoparticles reversed sociability deficit, social memory deficit, and anxiety-like and repetitive behaviors induced by VPA, and restored the oxidative stress indicators and apoptosis biomarkers in the hippocampus. This neurochemical effect must be associated with the reversal of ASD-like behaviors. These results provide evidence that lutein-loaded nanoparticles are an alternative treatment for VPA-induced behavioral damage in female rats and suggest the involvement of oxidative stress.