Acetyl-L-carnitine and/or liposomal co-enzyme Q10 prevent propionic acid-induced neurotoxicity by modulating oxidative tissue injury, inflammation, and ALDH1A1-RA-RARα signaling in rats

Alhusaini, A, Sarawi, W, Mattar, D, Abo-Hamad, A, Almogren, R, Alhumaidan, S, Alsultan, E, Alsaif, S, Hasan, I, Hassanein, E and Mahmoud, Ayman M ORCID: https://orcid.org/0000-0003-0279-6500 (2022) Acetyl-L-carnitine and/or liposomal co-enzyme Q10 prevent propionic acid-induced neurotoxicity by modulating oxidative tissue injury, inflammation, and ALDH1A1-RA-RARα signaling in rats. Biomedicine and Pharmacotherapy, 153. 113360. ISSN 0753-3322

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Official URL: http://dx.doi.org/10.1016/j.biopha.2022.113360

Abstract

Propionic acid (PPA) is a short-chain fatty acid produced endogenously by gut microbiota and found in foodstuffs and pharmaceutical products as an additive. Exposure to PPA has been associated with the development of autism spectrum disorder (ASD). The purpose of this study was to investigate the protective effect of acetyl‐L‐carnitine (ALCAR) and liposomal Co-enzyme Q10 (CoQ10) against cerebral and cerebellar oxidative injury, inflammation, and cell death, and alterations in ALDH1A1-RA-RARα signaling in an autism-like rat model induced by PPA. The rats were treated with PPA and concurrently received ALCAR and/or CoQ10 for 5 days. The animals were sacrificed, and the cerebral cortex and cerebellum were collected for analysis. PPA caused histopathological alterations along with increased malondialdehyde (MDA), NF-κB p65, TNF-α, and IL-6 in the cerebrum and cerebellum of rats. Reduced glutathione (GSH) and antioxidant enzymes were declined in the brain of rats that received PPA. Concurrent treatment with ALCAR and/or CoQ10 prevented tissue injury, decreased MDA, NF-κB p65, and pro-inflammatory cytokines, and enhanced cellular antioxidants in PPA-administered rats. ALCAR and/or CoQ10 upregulated Bcl-2 and decreased Bax and caspase-3 in the brain of rats. In addition, ALCAR and/or CoQ10 upregulated cerebral and cerebellar ALDH1A1 and RARα in PPA-treated rats. The combination of ALCAR and CoQ10 showed more potent effects when compared with the individual treatments. In conclusion, ALCAR and/or CoQ10 prevented tissue injury, ameliorated oxidative stress, inflammatory response, and apoptosis, and upregulated ALDH1A1-RA-RARα signaling in the brain of autistic rats.

Item Type:	Article (Article)
Peer-reviewed:	Yes
Date Deposited:	02 May 2024 17:50
Publisher:	Elsevier
Additional Information:	This is an open access article published in Biomedicine and Pharmacotherapy, by Elsevier.
Divisions:	Faculties > Science and Engineering
Subject terms:	Animals, Rats, Neurotoxicity Syndromes, Inflammation, Propionates, Ubiquinone, Acetylcarnitine, NF-kappa B, Antioxidants, Oxidative Stress, Autism Spectrum Disorder, Autism, Carnitine, Co-enzyme Q10, Inflammation, Oxidative stress, Retinoic acid, Acetylcarnitine, Animals, Antioxidants, Autism Spectrum Disorder, Inflammation, NF-kappa B, Neurotoxicity Syndromes, Oxidative Stress, Propionates, Rats, Ubiquinone, 1115 Pharmacology and Pharmaceutical Sciences, Oncology & Carcinogenesis
Data Access Statement:	The manuscript contains all data supporting the reported results.
URI:	https://e-space.mmu.ac.uk/id/eprint/634553
DOI:	https://doi.org/10.1016/j.biopha.2022.113360
ISSN	0753-3322
e-ISSN	1950-6007

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