Evidence map›Paper›PMID 39548593›Full record

ArticleBMC pharmacology & toxicology2024

An in vivo and in silico probing of the protective potential of betaine against sodium fluoride-induced neurotoxicity.

Solomon E Owumi, Bayode J Oluwawibe, Joseph Chimezie, Jesutosin J Babalola, Oludare M Ogunyemi, Gideon A Gyebi, Moses T Otunla, Ahmad Altayyar, Uche O Arunsi, Chioma E Irozuru and 1 more

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Article in BMC pharmacology & toxicology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

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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

11 authors.

Solomon E OwumiCancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, 200004, Nigeria. zicri@hotmail.com.
Bayode J OluwawibeCancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, 200004, Nigeria.
Joseph ChimezieEndocrine and Metabolic Research Laboratory, Department of Physiology, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, 200004, Nigeria.
Jesutosin J BabalolaNutritional and Industrial Biochemistry Unit, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
Oludare M OgunyemiNutritional and Industrial Biochemistry Unit, Department of Biochemistry, University of Ibadan, Ibadan, Nigeria.
Gideon A GyebiDepartment of Biochemistry, Faculty of Science and Technology, Bingham University, Nasarawa, Nigeria.
Moses T OtunlaCancer Research and Molecular Biology Laboratories, Department of Biochemistry, Faculty of Basic Medical Sciences, University of Ibadan, Ibadan, 200004, Nigeria.
Ahmad AltayyarBiodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, NG7 2RD, UK.
Uche O ArunsiSchool of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA, 30332-0400, USA.
Chioma E IrozuruDepartment of Chemistry and Biochemistry, Montana State University, Bozeman, MT, 59717, USA.
Olatunde O OwoeyeNeuroanatomy Research Laboratories, Department of Anatomy, University of Ibadan, Ibadan, Nigeria.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Excessive fluoride exposure beyond the tolerable limit may adversely impacts brain functionality. Betaine (BET), a trimethyl glycine, possesses antioxidant, anti-inflammatory and anti-apoptotic functions, although the underlying mechanisms of the role of BET on fluoride-induced neurotoxicity remain unelucidated. To assess the mechanism involved in the neuro-restorative role of BET on behavioural, neurochemical, and histological changes, we employed a rat model of sodium fluoride (NaF) exposure. Animals were treated with NaF (9 mg/kg) body weight (bw) only or co-treated with BET (50 and 100 mg/kg bw) orally uninterrupted for 28 days. We obtained behavioural phenotypes in an open field, performed negative geotaxis, and a forelimb grip test, followed by oxido-inflammatory, apoptotic, and histological assessment. Behavioural endpoints indicated lessened locomotive and motor and heightened anxiety-like performance and upregulated oxidative, inflammatory, and apoptotic biomarkers in NaF-exposed rats. Co-treatment with BET significantly enhanced locomotive, motor, and anxiolytic performance, increased the antioxidant signalling mechanisms and demurred oxidative, inflammatory, and apoptotic biomarkers and histoarchitectural damage in the cerebrum and cerebellum cortices mediated by NaF. The in-silico analysis suggests that multiple hydrogen bonds and hydrophobic interactions of BET with critical amino acid residues, including arginine (ARG380 and ARG415) in the Keap1 Kelch domain, which may disrupt Keap1-Nrf2 complex and activate Nrf2. This may account for the observed increased in the Nrf2 levels, elevated antioxidant response and enhanced anti-inflammatory response. The BET-Keap1 complex was also observed to exhibit structural stability and conformational flexibility in solvated biomolecular systems, as indicated by the thermodynamic parameters computed from the trajectories obtained from a 100 ns full atomistic molecular dynamics simulation. Therefore, BET mediates neuroprotection against NaF-induced cerebro-cerebellar damage through rats' antioxidant, anti-inflammatory, and anti-apoptotic activity, which molecular interactions with Keap1-Nrf2 may drive.

Indexed as

BetaineNeuroprotective AgentsSodium FluorideAnimalsAntioxidantsApoptosisBehavior, AnimalBrainComputer SimulationKelch-Like ECH-Associated Protein 1MaleMolecular Docking SimulationNeurotoxicity SyndromesNF-E2-Related Factor 2Oxidative StressRatsAntioxidantsBetaineKEAP1 protein, ratKelch-Like ECH-Associated Protein 1Neuroprotective AgentsNfe2l2 protein, ratNF-E2-Related Factor 2Sodium FluorideBetaineMolecular dockingMolecular dynamics simulationNeurotoxicityOxidative stressSodium fluoride

Identifiers

PMID39548593
PMCPMC11568634

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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 OpenQuestion graph.