Selected biomarkers as predictive tools in testing efficacy of melatonin and coenzyme Q on propionic acid - induced neurotoxicity in rodent model of autism

BMC Neuroscience

Research Article

Laila Al-Ayadhi¹  Mashael Al-Ghamdi²  Afaf El-Ansary³ 

[1] Autism Research and Treatment Center, Riyadh, Saudi Arabia;Shaik AL-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia;Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia;Biochemistry Department, Science College, King Saud University, P.O box 22452, Zip code 11495, Riyadh, Saudi Arabia;Biochemistry Department, Science College, King Saud University, P.O box 22452, Zip code 11495, Riyadh, Saudi Arabia;Autism Research and Treatment Center, Riyadh, Saudi Arabia;Shaik AL-Amodi Autism Research Chair, King Saud University, Riyadh, Saudi Arabia;Therapuetical Chemistry Department, National Research Centre, Dokki, Cairo, Egypt;

关键词: Propionic acid;    Melatonin;    Coenzyme Q;    Serotonin;    Gamma amino-butyric acid;    Dopamine;    Oxytocin;    Interferon γ-inducible protein 16;    Comet DNA;    Autism;   

DOI  :  10.1186/1471-2202-15-34

 received in 2013-10-30, accepted in 2014-02-19,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundExposures 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.ResultsThe 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.ConclusionIn 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.

【 授权许可】

Unknown   
© Al-Ghamdi et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.