Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism
Open accessAbstract
BACKGROUND: Exposures to environmental toxins are now thought to contribute to the development of autism spectrum disorder. Propionic acid (PA) found as a metabolic product of gut bacteria has been reported to mimic/mediate the neurotoxic effects of autism. Results from animal studies may guide investigations on human populations toward identifying environmental contaminants that produce or drugs that protect from neurotoxicity. Forty-eight young male Western Albino rats were used in the present study. They were grouped into six equal groups 8 rats each. The first group received a neurotoxic dose of buffered PA (250 mg/Kg body weight/day for 3 consecutive days). The second group received only phosphate buffered saline (control group). The third and fourth groups were intoxicated with PA as described above followed by treatment with either coenzyme Q (4.5 mg/kg body weight) or melatonin (10 mg/kg body weight) for one week (therapeutically treated groups). The fifth and sixth groups were administered both compounds for one week prior to PA (protected groups). Heat shock protein70 (Hsp70), Gamma amino-butyric acid (GABA), serotonin, dopamine, oxytocin and interferon γ-inducible protein 16 together with Comet DNA assay were measured in brain tissues of the six studied groups. RESULTS: The obtained data showed that PA caused multiple signs of brain toxicity revealed in depletion of GABA, serotonin, and dopamine, are which important neurotransmitters that reflect brain function, interferon γ-inducible protein 16 and oxytocin. A high significant increase in tail length, tail DNA% damage and tail moment was reported indicating the genotoxic effect of PA. Administration of melatonin or coenzyme Q showed both protective and therapeutic effects on PA-treated rats demonstrated in a remarkable amelioration of most of the measured parameters. CONCLUSION: In conclusion, melatonin and coenzyme Q have potential protective and restorative effects against PA-induced brain injury, confirmed by improvement in biochemical markers and DNA double strand breaks.
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Propionate modulates 5-HT secretion in the gut and depletes 5-HT and dopamine levels in the brain, which could contribute to hyperserotonemia observed in children with ASD.
“In addition to direct effects on the brain, propionate has been shown to modulate 5-hydroxytryptamine (5’-HT) secretion in the gut and deplete 5’-HT and dopamine levels in the brain, which could potentially contribute to the hyperserotonemia observed in children with ASD [182,183,184].”
From Autism, Gastrointestinal Symptoms and Modulation of Gut Microbiota by Nutritional Interventions (2019) · cites this paper as [184]
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- Authors
- Al-Ghamdi, M., Al-Ayadhi, L., & El-Ansary, A.
- Affiliations
- King Saud University (SA)
- Corresponding author
- El-Ansary, Afaf
- Venue
- BMC Neuroscience
- Published
- 2014-02-25
- Volume
- 15
- Issue
- 1
- Pages
- 34-34
- ISSN
- 1471-2202 (ISSN-L)
- PMC
- PMC3996043
- OpenAlex
- W2140618002
- Cited by
- 25
- References
- 57
- Citations by year
- 2026: 1 · 2025: 3 · 2023: 3 · 2021: 5 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 1 · 2015: 4 · 2014: 1
- FWCI
- 1.30
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Neuroscience (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- King Saud University
- King Abdulaziz City for Science and Technology
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- propionic acid, autism spectrum disorder, melatonin, coenzyme Q10, neuroprotection, neurotoxicity, biomarkers, HSP70, GABA, serotonin, dopamine, oxytocin, genotoxicity, DNA damage, environmental toxins
- MeSH terms
- Animals, Autistic Disorder, Male, Melatonin, Nerve Tissue Proteins, Prognosis, Propionates, Sensitivity and Specificity, Ubiquinone, Reproducibility of Results, Biomarkers, Treatment Outcome, Rats, Wistar, Neurotransmitter Agents, Neuroprotective Agents, Rats
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