Effects of artichoke extracts and probiotic on maternal immunological activation, valproic acid-induced oxidative stress, and gut leakiness in a rat model of autism

Abstract

Maternal health during pregnancy is a leading factor influencing offspring risk. This study investigated whether postnatal dietary supplementation could reduce oxidative stress and gut leakiness in a rat model of autism spectrum disorder (ASD). Male rat pups were prenatally exposed to valproic acid (VPA) or lipopolysaccharide (LPS) to induce ASD-like conditions. A total of 54 offspring of Wistar albino rats were divided into nine groups to evaluate various postnatal treatments, including an artichoke-based prebiotic (AR), probiotics (Pro), and omega-3 fatty acids (ω3). The experimental design also included control groups (saline, VPA-only, and LPS-only), as well as a protective regimen in which AR was administered both prenatally and postnatally. Oxidative stress and gut permeability “leakiness” were assessed using Enzyme-Linked Immunosorbent Assay (ELISA). Prenatal exposure to VPA and LPS was associated with increased oxidative stress levels in brain homogenates, accompanied by a significant decrease in glutathione (GSH). Additionally, elevated plasma levels of gut permeability biomarkers were observed. In the VPA model, treatment with artichoke-derived prebiotics – administered either prenatally, postnatally, or in combination with probiotics – effectively improved oxidative stress markers, as evidenced by a significant increase in GSH levels. Conversely, similar interventions in the LPS-induced maternal immune activation model did not significantly ameliorate oxidative stress, although a modest increase in GSH levels was noted. Plasma levels of gut permeability biomarkers did not show significant improvement in either model following treatment with artichoke-derived probiotics alone or in combination with probiotics and omega-3 fatty acids. However, intestinal fatty acid-binding protein levels were significantly reduced in all treatment groups across both models. In contrast, lipopolysaccharide-binding protein (LBP) levels were not significantly reduced by artichoke extract monotherapy in either model, although combination therapy with probiotics and/or omega-3s led to significant reductions in LBP. These results support the use of both VPA and LPS as complementary models for studying ASD. The VPA model, characterized by direct and predictable neurotoxic effects, appears to be more suitable for evaluating preventive interventions. In contrast, the LPS model more accurately captures the complex immune-inflammatory mechanisms implicated in ASD, highlighting the need for broader and more individualized treatment strategies. The differing responses to artichoke-based interventions in these models underscore the importance of considering ASD etiology when designing dietary and microbiome-targeted therapies.