Evidence mapPaperPMID 39350139Full record

ArticleBehavioral and brain functions : BBF2024

Comparative effect of atorvastatin and risperidone on modulation of TLR4/NF-κB/NOX-2 in a rat model of valproic acid-induced autism.

Eman A E Farrag, Mona H Askar, Zienab Abdallah, Safinaz M Mahmoud, Eman A Abdulhai, Eman Abdelrazik, Eman Mohamad El Nashar, Faten Mohammed Alasiri, Asma Nasser Saeed Alqahtani, Mamdouh Eldesoqui and 2 more

Abstract readComparative Study
In one paragraph

Article in Behavioral and brain functions : BBF, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Review
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors.

Eman A E FarragDepartment of Clinical Pharmacology, Faculty of Medicine, Mansoura University, Mansoura, 31516, Egypt. dreman_abdo_2010@mans.edu.eg.ORCID https://orcid.org/0000-0003-2567-9665
Mona H AskarDepartment of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Zienab AbdallahDepartment of Medical Physiology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Safinaz M MahmoudDepartment of Medical Histology and Cell Biology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Eman A AbdulhaiDepartment of Pediatrics, Faculty of Medicine, Mansoura, University, Mansoura, Egypt.
Eman AbdelrazikDepartment of Forensic Medicine and Clinical Toxicology, Faculty of Medicine, Mansoura University, Mansoura, Egypt.
Eman Mohamad El NasharDepartment of Anatomy, College of Medicine, King Khalid University, 62529, Abha, Saudi Arabia.ORCID https://orcid.org/0000-0002-2883-6761
Faten Mohammed AlasiriKing Fahad Armed Forces Hospital, Khamis Mushatt, Saudi Arabia.
Asma Nasser Saeed AlqahtaniBin Rushed Center, Khamis Mushait, Saudi Arabia.
Mamdouh EldesoquiDepartment of Basic Medical Sciences, College of Medicine, AlMaarefa University, 13713, Diriyah, Riyadh, Saudi Arabia.
Ali M EldibDepartment of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt.
Alshimaa MagdyDepartment of Medical Biochemistry, Faculty of Medicine, Mansoura University, Mansoura, Egypt.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundAutism spectrum disorder (ASD) is a complex neurodevelopmental condition that is significantly increasing, resulting in severe distress. The approved treatment for ASD only partially improves the sympoms, but it does not entirely reverse the symptoms. Developing novel disease-modifying drugs is essential for the continuous improvement of ASD. Because of its pleiotropic effect, atorvastatin has been garnered attention for treating neuronal degeneration. The present study aimed to investigate the therapeutic effects of atorvastatin in autism and compare it with an approved autism drug (risperidone) through the impact of these drugs on TLR4/NF-κB/NOX-2 and the apoptotic pathway in a valproic acid (VPA) induced rat model of autism.

methodsOn gestational day 12.5, pregnant rats received a single IP injection of VPA (500 mg/kg), for VPA induced autism, risperidone and atorvastatin groups, or saline for control normal group. At postnatal day 21, male offsprings were randomly divided into four groups (n = 6): control, VPA induced autism, risperidone, and atorvastatin. Risperidone and atorvastatin were administered from postnatal day 21 to day 51. The study evaluated autism-like behaviors using the three-chamber test, the dark light test, and the open field test at the end of the study. Biochemical analysis of TLR4, NF-κB, NOX-2, and ROS using ELISA, RT-PCR, WB, histological examination with hematoxylin and eosin and immunohistochemical study of CAS-3 were performed.

resultsMale offspring of prenatal VPA-exposed female rats exhibited significant autism-like behaviors and elevated TLR4, NF-κB, NOX-2, ROS, and caspase-3 expression. Histological analysis revealed structural alterations. Both risperidone and atorvastatin effectively mitigated the behavioral, biochemical, and structural changes associated with VPA-induced rat model of autism. Notably, atorvastatin group showed a more significant improvement than risperidone group.

conclusionsThe research results unequivocally demonstrated that atorvastatin can modulate VPA-induced autism by suppressing inflammation, oxidative stress, and apoptosis through TLR4/NF-κB/NOX-2 signaling pathway. Atorvastatin could be a potential treatment for ASD.

Indexed as

AtorvastatinDisease Models, AnimalNADPH Oxidase 2NF-kappa BRisperidoneToll-Like Receptor 4Valproic AcidAnimalsApoptosisAutism Spectrum DisorderAutistic DisorderFemaleMalePregnancyRatsRats, Sprague-DawleyAtorvastatinCybb protein, ratNADPH Oxidase 2NF-kappa BRisperidoneTlr4 protein, ratToll-Like Receptor 4Valproic AcidApoptosisAtorvastatinAutismNF-κBRisperidoneTLR4Valproic acid

Identifiers

PMID39350139
PMCPMC11742802

What Socratic holds

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LicenceCC BY-NC-ND
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.