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

Abstract

Autism is a neuropathology characterized by behavioral disorders. Considering that oxidative stress is involved in the pathophysiology of this disease, we evaluated the effects of quercetin, a flavonoid with antioxidant and neuroprotective properties, in an experimental model of autism induced by valproic acid (VPA). Twelve pregnant female rats were divided into four groups (control, quercetin, VPA, and VPA+quercetin). Quercetin (50 mg/kg) was administered orally to the animals from gestational days 6.5 to 18.5, and VPA (800 mg/kg) was administered orally in a single dosage on gestational day 12.5. Behavioral tests such as open field, social interaction, and tail flick nociceptive assays were performed on pups between 30 and 40 days old, after which the animals were euthanized. Cerebral cortex, hippocampus, striatum, and cerebellum were collected for evaluation of oxidative stress parameters. The pups exposed to VPA during the gestational period showed reduced weight gain, increased latency in the open field and tail flick tests, reduced time of social interaction, accompanied by changes in oxidative stress parameters mainly in the hippocampus and striatum. Prenatal treatment with quercetin prevented the behavioral changes and damage caused by oxidative stress, possibly due to its antioxidant action. Our findings demonstrated that quercetin has neuroprotective effects in an animal model of autism, suggesting that this natural molecule could be an important therapeutic agent for treatment of autism spectrum disorders (ASDs).

Inhibition of the ERK1/2 Phosphorylation by Dextromethorphan Protects against Core Autistic Symptoms in VPA Induced Autistic Rats: In Silico and in Vivo Drug Repurposition Study

“…59 In a study by de Mattos et al, the pups of the VPA exposed rats were accompanied by changes in the oxidative stress parameters in the brain. 60 The standard treatment group (risperidone: 2.5 mg/kg) showed a significant reversal in the reduced glutathione levels (p = 0.045), SOD (p = 0.009), and catalase (p = 0.003) on comparing to the VPA treated groups. No significant results were found on treatment with 10 and 15 mg/kg doses of dextromethorphan when compared to diseased control groups.…”

“…Data from various studies including both the clinical and the preclinical studies revealed elevated oxidative stress levels and declined antioxidant levels in the brains of autistic patients . In a study by de Mattos et al, the pups of the VPA exposed rats were accompanied by changes in the oxidative stress parameters in the brain . The standard treatment group (risperidone: 2.5 mg/kg) showed a significant reversal in the reduced glutathione levels ( p = 0.045), SOD ( p = 0.009), and catalase ( p = 0.003) on comparing to the VPA treated groups.…”

Neuroprotective Effects of Quercetin in Pediatric Neurological Diseases

“…In an open-label pilot study, it effectively reduced symptoms without any adverse effects [67] Developmental hypothyroidism rat model Recovered expression of NQO1 and Txn1, restored NeuN-positive granule cells, parvalbumin and somatostatin-positive interneurons and recovered the expressions of Otx2 and Gria3 [68] Prenatal model in rats induced by valproic acid Prevented behavioral changes, alterations in total thiol content and changes of SOD, CAT and GST in the hippocampus, prevented the alterations of CAT and GPx in the cerebellum, prevented the increase of ROS, nitrite and TBARS levels in the striatum and prevented nitrite and CAT alterations in the cerebral cortex [69] Type of Study in ADHD Effects References…”

“…The AGIQ-recovered expression of some antioxidant enzyme genes such as NQO1 and thioredoxin 1 (Txn1) in the developmental hypothyroidism rats also restored of NeuN-positive post-mitotic granule cells, parvalbumin and somatostatin-positive interneurons and both antioxidants recovered expression of GABAergic interneuron-related gene orthodenticle homeobox 2 (Otx2) and also AGIQ-recovered expression of glutamate ionotropic receptor AMPA type subunit 3 (Gria3), thereby reversing the disruptive neurogenesis through compensatory responses [68]. Recently, in an experimental model of autism induced by valproic acid during the gestational period, the prenatal treatment with quercetin prevented the behavioral changes and also the treatment with quercetin prevented alterations in the total thiol content as well as changes in the activities of SOD, CAT and glutathione-S-transferase (GST) enzymes in the hippocampus, which in turn prevented the alterations in the CAT and GPx activity in the cerebellum to thereby prevent an increase in the level of ROS, nitrite and thiobarbituric acid reactive substances (TBARS) levels in the striatum and that in the nitrite and CAT alterations in the cerebral cortex [69]. Thus, compounds that contain quercetin can improve the antioxidant defense mechanism.…”

Quercetin: A Bioactive Compound Imparting Cardiovascular and Neuroprotective Benefits: Scope for Exploring Fresh Produce, Their Wastes, and By-Products

“…The hydroalcoholic extract of coffee silverskin containing quercetin along with other polyflavonoids was reported for its neurodegenerative activity attributed to counteract oxidative stress and maintain cell viability [95]. The neuroprotective activities in rats using quercetin were determined by de Mattos et al [96]. The neuroprotective properties of quercetin for treating autism in an animal model is being hypothesized as an important therapeutic candidate for addressing neurological disorders such as autism spectrum disorders (ASDs).…”