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

Afaf El-Ansary¹  Laila Al-Ayadhi²  Mashael Al-Ghamdi³ 

[1]Therapuetical Chemistry Department, National Research Centre, Dokki, Cairo, Egypt

[2]Department of Physiology, Faculty of Medicine, King Saud University, Riyadh, Saudi Arabia

[3]Biochemistry Department, Science College, King Saud University, P.O box 22452, Zip code 11495 Riyadh, Saudi Arabia

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

Others  :  1092139
DOI  :  10.1186/1471-2202-15-34

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

【 摘 要 】

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.

【 授权许可】

   
2014 Al-Ghamdi et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 7.

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