Postnatal treatment using curcumin supplements to amend the damage in VPA-induced rodent models of autism

Abstract

BackgroundValproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism.MethodsThe study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12.5th day of gestation. At 7 days from their birth, the animals were supplemented with a specific dose of curcumin. Forty neonatal male Western Albino rats were divided into four groups. Rats in group I received only phosphate-buffered saline, rats in group II were the prenatal VPA exposure newborns, rats in group III underwent prenatal VPA exposure supplemented with postnatal curcumin, and rats in group IV were given only postnatal curcumin supplements.ResultsVPA rats exhibited delayed maturation and lower body and brain weights with numerous signs of brain toxicity, such as depletion of IFN-γ, serotonin, glutamine, reduced glutathione, glutathione S-transferase, lipid peroxidase with an increase in CYP450, IL-6, glutamate, and oxidized glutathione. A curcumin supplement moderately corrected these dysfunctions and was especially noticeable in improving delayed maturation and abnormal weight.ConclusionsCurcumin plays a significant therapeutic role in attenuating brain damage that has been induced by prenatal VPA exposure in rats; however, its therapeutic role as a dietary supplement still must be certified for use in humans.Electronic supplementary materialThe online version of this article (doi:10.1186/s12906-017-1763-7) contains supplementary material, which is available to authorized users.

Quercetin prevents alterations of behavioral parameters, delta‐aminolevulinic dehydratase activity, and oxidative damage in brain of rats in a prenatal model of autism

“…The animal model of autism induced by VPA is described in the literature as an alternative to investigate behavioral and biochemical changes in rodents similar to those found in individuals with ASD (Mabunga, Gonzales, Kim, Kim, & Shin, 2015). In our study, VPA was administered orally in pregnant rats and the behavioral changes of the pups were similar to those described in other studies when VPA was administered intraperitoneally (Al‐amin et al, 2015; Al‐askar, Bhat, Selim, Al‐Ayadhi, & El‐Ansary, 2017; Bambini‐Junior et al, 2014; Schneider & Przewłocki, 2005). The possible mechanisms involved in VPA‐induced autism‐like behavior in rats include oxidative damage in fetal brain, inhibition of histone deacetylase (promoting increased neuronal death of rat embryos by apoptosis), and imbalance of the GABAergic inhibitory/excitatory system mainly in the hippocampus, generating epileptic seizures and hyperserotonemia (Mabunga et al, 2015).…”

Beneficial effects of pioglitazone, a selective peroxisome proliferator‐activated receptor‐γ agonist in prenatal valproic acid‐induced behavioral and biochemical autistic like features in Wistar rats

“…Few studies revealed the increase in oxidative stress due to deficiency of antioxidants lead to anxiety and low exploratory activity in rodents (Desrumaux et al, 2005; de Oliveira et al, 2007). The excitotoxicity or release of glutamate is considered one of the primary reasons for generation of reactive species and to disrupt the glutathione homeostasis in (brain and plasma) both VPA‐rodent model and clinical subjects (Al‐Askar et al, 2017; El‐Ansary, 2016). Therefore, oxidative stress has been linked to ASD and undoubtedly played a significant role in its etiology.…”

Nrf2 Activators as Dietary Phytochemicals Against Oxidative Stress, Inflammation, and Mitochondrial Dysfunction in Autism Spectrum Disorders: A Systematic Review

“…Besides, curcumin up-regulated the expression of neurons in hippocampal DG and CA3 regions and down-regulated the expression of astrocytes (48). On the other hand, Al-Askar et al demonstrated that postnatal curcumin treatment reversed various impaired parameters (i.e., IFN-γ, serotonin, glutamine, GSH, glutathione S-transferase, lipid peroxidase, CYP450, IL-6, glutamate, and GSSG) in the VPA model (49). Especially, curcumin improved delayed maturation and abnormal weight (49).…”