Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats

Objective(s): Trans-sodium crocetinate (TSC) is one of the crocetin derivations that is more soluble and stable than crocetin and its cis form. It easily crosses the blood-brain barrier. TSC has neuroprotective effects. Bisphenol A (BPA) is an endocrine-mimicking compound that induces Parkinson-like...

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Main Authors: Majid Keshavarzi, Bibi Marjan Razavi, Hossein Hosseinzadeh
Format: Article
Language:English
Published: Mashhad University of Medical Sciences 2025-02-01
Series:Iranian Journal of Basic Medical Sciences
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Online Access:https://ijbms.mums.ac.ir/article_25269_4b2b6d68311b498a4a2457009d56cb7a.pdf
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author Majid Keshavarzi
Bibi Marjan Razavi
Hossein Hosseinzadeh
author_facet Majid Keshavarzi
Bibi Marjan Razavi
Hossein Hosseinzadeh
author_sort Majid Keshavarzi
collection DOAJ
description Objective(s): Trans-sodium crocetinate (TSC) is one of the crocetin derivations that is more soluble and stable than crocetin and its cis form. It easily crosses the blood-brain barrier. TSC has neuroprotective effects. Bisphenol A (BPA) is an endocrine-mimicking compound that induces Parkinson-like disease by impacting the dopaminergic system. In this research, the effects of TSCs on BPA-induced Parkinson-like symptoms via behavioral and molecular assays have been investigated.Materials and Methods: Male Wistar rats received BPA (75 mg/kg, gavage), TSC (10, 20, and 40 mg/kg), and levodopa (L-dopa) (10 mg/kg) via intraperitoneal injection (IP) for 28 days. Parkinsonian-like motor features were evaluated using bar test, rotarod, and open field experiments. Malondialdehyde (MDA) and glutathione (GSH) levels were also measured as the most important indicators of oxidative stress. Western blotting was performed for the molecular assays of alpha-synuclein (α-syn), Bcl-2, Bax, caspase-3, Beclin, and LC3 I/II proteins. Results: Our analyses indicated that treatment with TSC at high dose reduces MDA levels and protects GSH reserves. TSC can also increase anti-apoptotic Bcl-2 and decrease pro-apoptotic Bax and Caspase-3 proteins. While it does not affect autophagy markers, TSC decreased α-syn protein expression, reduced the catalepsy time, and improved the time spent staying on the rotating bar and the locomotor activity.  Conclusion: Overall, TSC likely ameliorates BPA-mediated Parkinson’ s-like symptoms by suppressing oxidative stress inhibition. This leads to reduced α-syn expression, which ultimately results in apoptosis inductions. Therefore, TSC can serve as a promising exploratory target for future research aimed at controlling Parkinson’s disease.
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spelling doaj-art-07f0f6dcec5e4e17a0a7d4a861ca17822025-08-20T03:56:45ZengMashhad University of Medical SciencesIranian Journal of Basic Medical Sciences2008-38662008-38742025-02-0128225426310.22038/ijbms.2024.81157.1756725269Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in ratsMajid Keshavarzi0Bibi Marjan Razavi1Hossein Hosseinzadeh2Department of Pharmacodynamics and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmacodynamics and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranDepartment of Pharmacodynamics and Toxicology, Faculty of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IranObjective(s): Trans-sodium crocetinate (TSC) is one of the crocetin derivations that is more soluble and stable than crocetin and its cis form. It easily crosses the blood-brain barrier. TSC has neuroprotective effects. Bisphenol A (BPA) is an endocrine-mimicking compound that induces Parkinson-like disease by impacting the dopaminergic system. In this research, the effects of TSCs on BPA-induced Parkinson-like symptoms via behavioral and molecular assays have been investigated.Materials and Methods: Male Wistar rats received BPA (75 mg/kg, gavage), TSC (10, 20, and 40 mg/kg), and levodopa (L-dopa) (10 mg/kg) via intraperitoneal injection (IP) for 28 days. Parkinsonian-like motor features were evaluated using bar test, rotarod, and open field experiments. Malondialdehyde (MDA) and glutathione (GSH) levels were also measured as the most important indicators of oxidative stress. Western blotting was performed for the molecular assays of alpha-synuclein (α-syn), Bcl-2, Bax, caspase-3, Beclin, and LC3 I/II proteins. Results: Our analyses indicated that treatment with TSC at high dose reduces MDA levels and protects GSH reserves. TSC can also increase anti-apoptotic Bcl-2 and decrease pro-apoptotic Bax and Caspase-3 proteins. While it does not affect autophagy markers, TSC decreased α-syn protein expression, reduced the catalepsy time, and improved the time spent staying on the rotating bar and the locomotor activity.  Conclusion: Overall, TSC likely ameliorates BPA-mediated Parkinson’ s-like symptoms by suppressing oxidative stress inhibition. This leads to reduced α-syn expression, which ultimately results in apoptosis inductions. Therefore, TSC can serve as a promising exploratory target for future research aimed at controlling Parkinson’s disease.https://ijbms.mums.ac.ir/article_25269_4b2b6d68311b498a4a2457009d56cb7a.pdfalpha-synucleinapoptosisautophagybisphenol aparkinson’s diseasesaffron
spellingShingle Majid Keshavarzi
Bibi Marjan Razavi
Hossein Hosseinzadeh
Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats
Iranian Journal of Basic Medical Sciences
alpha-synuclein
apoptosis
autophagy
bisphenol a
parkinson’s disease
saffron
title Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats
title_full Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats
title_fullStr Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats
title_full_unstemmed Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats
title_short Trans-sodium crocetinate ameliorates Parkinson-like disease caused by bisphenol A through inhibition of apoptosis and reduction of α-synuclein in rats
title_sort trans sodium crocetinate ameliorates parkinson like disease caused by bisphenol a through inhibition of apoptosis and reduction of α synuclein in rats
topic alpha-synuclein
apoptosis
autophagy
bisphenol a
parkinson’s disease
saffron
url https://ijbms.mums.ac.ir/article_25269_4b2b6d68311b498a4a2457009d56cb7a.pdf
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