Evidence map›Paper›PMID 39520654›Full record

ArticleMolecular neurobiology2025

Molecular and Behavioral Neuroprotective Effects of Clavulanic Acid and Crocin in Haloperidol-Induced Tardive Dyskinesia in Rats.

Parisa Shoae-Hagh, Bibi Marjan Razavi, Hamid Reza Sadeghnia, Soghra Mehri, Gholamreza Karimi, Hossein Hosseinzadeh

Abstract read
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In one paragraph

Article in Molecular neurobiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Review
  3. Article
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

6 authors.

Parisa Shoae-HaghStudent Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.ORCID http://orcid.org/0000-0002-5890-0947
Bibi Marjan RazaviDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. razavimr@mums.ac.ir.ORCID http://orcid.org/0000-0002-7450-9286
Hamid Reza SadeghniaPharmacological Research Center of Medicinal Plants, Mashhad University of Medical Sciences, Mashhad, Iran.ORCID http://orcid.org/0000-0002-3228-6897
Soghra MehriDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.ORCID http://orcid.org/0000-0002-9697-2343
Gholamreza KarimiDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.ORCID http://orcid.org/0000-0002-1273-5448
Hossein HosseinzadehDepartment of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran. hosseinzadehh@mums.ac.ir.ORCID http://orcid.org/0000-0002-3483-851X

Funding

Mashhad University of Medical Sciences Vice-Chancellor for Research 941406
6 · The paper itself

Abstract

Clavulanic acid (ClvA), a beta-lactamase inhibitor, is being explored for its significant neuroprotective potential. The effects of ClvA were assessed both individually and in combination with crocin (Cr), an antioxidant derived from saffron, in the context of tardive dyskinesia (TD). In rat haloperidol (Hp)-induced-TD (1 mg/kg, i.p. 21 days), the effects of ClvA (50, 100, 150 mg/kg) and Cr (10, 20, 40 mg/kg) were assessed via vacuous chewing movements (VCM) and tongue protrusion (TP). Striatal malondialdehyde (MDA) and glutathione (GSH) were measured spectrophotometrically. Based on the results, ClvA (100 mg/kg) and Cr (10 mg/kg) were determined with sub-effective doses. Glutamate transporter-subtype1 (GLT1), dopamine active transporter (DAT), vesicular monoamine transporter-type2 (VMAT2), Bax/Bcl2, cleaved Caspase3, phosphorylated AKT/AKT, IL1β, and TNFα levels were quantified using western blotting in sub-effective doses and their combination. The behavioral results of catalepsy and orofacial dyskinesia demonstrated model establishment. Hp decreased GLT1 (p < 0.05), DAT (p < 0.01), VMAT2 (p < 0.001), GSH and pAKT/AKT (p < 0.0001); increased TNFα (p < 0.05), IL1β, cleaved Caspase3 (p < 0.001); MDA and Bax/Bcl2 (p < 0.0001). ClvA 100 mg/kg reversed the decreased GLT1 and VMAT2 (p < 0.01), alongside the increased MDA (p < 0.0001) and VCM (p < 0.05). It also increased AKT phosphorylation (p < 0.05). No effects were noted on DAT, GSH, Bax/Bcl2, or inflammatory factors. However, the combination with Cr at 10 mg/kg influenced ClvA on DAT (p < 0.01) and resulted in a significant increase in GSH (p < 0.0001). Additionally, there was a marked decrease in TNFα (p < 0.0001) and IL1β (p < 0.001), enhancing its effects on reducing MDA and increasing pAKT/AKT (p < 0.0001). The combination adversely affected GLT1. ClvA protects against TD via GLT1 and VMAT2; combined with Cr, it enhances antioxidant effects, improves DAT, and requires dose optimization for GLT1 disruption.

Indexed as

Behavior, AnimalCarotenoidsClavulanic AcidHaloperidolNeuroprotective AgentsTardive DyskinesiaAnimalsCorpus StriatumDopamine Plasma Membrane Transport ProteinsGlutathioneMaleMalondialdehydeProto-Oncogene Proteins c-aktRatsRats, Sprague-DawleyRats, WistarCarotenoidsClavulanic AcidcrocinDopamine Plasma Membrane Transport ProteinsGlutathioneHaloperidolMalondialdehydeNeuroprotective AgentsProto-Oncogene Proteins c-aktDopamine active transporterGlutamate transporterMovement disordersStriatumTardive dyskinesiaVesicular monoamine transporter type 2

Identifiers

PMID39520654

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

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.