الفهرس 
Aluminium and PollutionOnly 14 pages are availabe for public view
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Abstract
SUMMARY
Autism spectrum disorders (ASDs) are group of neurodevelopmental disorders characterized by persistent deficits in social communication, interactions with repetitive patterns of behaviors and restricted interests or activities.
The prevalence of autism was increased in the last few decades; data show that about 1 in 44 of children was identified with ASDs. It is four times common in males than females. The increased prevalence could not be explained by advances in diagnosis but multiple lines of evidence suggested that oxidative stress could represent the basis for the observed association between genetic immune-inflammation and environmental factors underlying autism spechum disorders, and suggested also a role of glutathione S-transferases polymorphism in ASD development. when taking into account the important role of GSTs enzyme in detoxification.
Aluminium is the third most common abundant metal on earth, that have changed the world, as it has been used extremely in the past five decades in every products, and we became exposed to many sources like aluminium cookwares, aluminium foil, food additives, medications, tap water and cosmetics; which raise our exposure to this metal, and we are facing the aluminium era with its bad effects on environoment and human health.
It has been proposed that aluminium exposure may contribute as an environomental factor that cause ASD and increase its frequency. Multiple studies reported the remarkable higher aluminium concentration in ASD children compared to the neurotypical one.
Study the role of glutathione S-transferase gene (GST) polymorphism and its relation to aluminium in children with ASD. The super family glutathions S-Transferases is composed of multiple isozymes with significant evidence of functional polymorphic variation. They are involved in phase ΙΙ detoxification of endogenous and xenobiotic compounds and polymorphisms in these genes may affect biologic responses to heavy metals.
The study of glutathione S-transferase mu (GSTM1) and glutathione S-Transferase theta (GSTT1) gene polymorphisms in ASD children is a new step toward better understanding the pathophysiology of this disorder, enabling predictive medicine.
The study was conducted into two parts. The first part was comparative case-control study comparing between the children with ASD and healthy control children, the study was started by 76 newly diagnosed with childhood autism and medication free for at least 3 months with age 2-8 years old compared to 30 healthy control children.
After exclusion of children with ASD with any syndromes associated with autistic features as Down syndrome and Fragile X syndrome, cases diagnosed with other pervasive developmental disorders, Rett’s syndrome, Asperger syndrome, childhood disintegrative disorders and cases with cerebral palsy.
The second part was an interventional study, using supplements rich in vitamin C, vitamin E and zinc given to the children with ASD for 3 months, then studying the differences in the levels of the previously studied parameters. All children with autism received the supplements, and the dosage was adjusted based on baseline measured body weight. A commercial supplement containing Zinc 10mg/5mL syrup was given as follows: 2.5 ml once daily up to 5 years old children and 5 ml once daily above 5 years old child. Vitamin E 400 mg was given once per day for children above 6 years and day after day for children below 6 years. Vitamin C 100 mg/ml (1 ml equal 20 drops) was given as follows: 10 drops per day for children 2-4 years old and 20 drops for 4 to 8 years old children. All supplements were given orally for 3 months.
After the supplements for three months there was dropout in the children with ASD and the remaining ASD children in the study were 30 children with ASD due to Corona pandemic.
In this study, we use hair analysis to evaluate the long-term aluminium exposure as a non-invasive best indicator of a given mineral in the body. Full medical history (appendix II) and clinical examination for all the patients and the control children were applied.
The children with ASD diagnosed using the Diagnostic and Statistical Manual of Mental Disorders 5th Edition criteria, as ASD children have been chosen from “Learning Disability and Neurorehabilitation Clinic”, Center of Excellence of Medical Research, National Research Centre, subdivision, and detection of severity of children with ASD by the Childhood Autism Rating Scale (CARS) (appendix III). The other control group have been chosen from relatives of children with ASD.
DNA extraction from white blood cells for screening of GST gene polymorphisms. Determination of glutathione S- transferase enzyme (GST) activity level in plasma. Determination of serum malondialdehyde (MDA) concentration and serum Nitric Oxide (NO) concentration.
The results of this study revealed that there were remarkable significant increases in aluminum hair levels in ASD children when compared to that of controls. Also, significant decrease in the GST enzyme activity with significant increase in the oxidative stress byproducts (MDA& NO) when compared to those of the control.
The ASD children of the study suffered from aluminum toxicity and a state of oxidative stress, the study also demonstrated the neurotoxic effect of the aluminium in ASD children by the positive correlation present between aluminium concentration in hair and the severity of ASD as measured by CARS and as a pro-oxidant by the negative correlation present between the aluminum concentration with the GSTs enzyme activity.
The genetic polymorphism (GSTM1, GSTT1) was studied, as the study showed that ASD children had a higher distribution of the combined null GSTM1&T1, compared to the control group. [O.R = 6.8, Confident interval (1.51 - 31.1)], indicated that children with this genotype were 6.8 times more likely to have autism spectrum disorder than those without this genotype. The combined null GSTM1&T1 genotype is the most common type of ASD, and this genotype did not protect the studied autism group against the toxic effect of aluminum by producing enough GST enzymes.
So, the plan of the study was to enhance the exhausted endogenous antioxidants (antioxidant defense mechanism) by exogenous antioxidant supplements, so we use the combined effects of vitamin E which is a lipid soluble, vitamin C which is water soluble that possess varying degree of BBB penetrance, zinc ions acts as the active centre in many kinds of enzymes. The results showed that supplements with vitamin E, vitamin C and zinc were found to be effective for treatment of the oxidative stress state as shown by decreasing in levels of oxidative biomarkers (MDA&NO) and increase in GST enzyme activity after supplements. As ensured by the significant negative correlation between oxidative biomarkers and GST after antioxidant supplements in the study.
Overall, spatial arrangement of vitamins C and E facilitates the efficient removal of free radicals, and combinations of vitamins and minerals may be of benefit in amelioration of oxidative stress among children with ASD due to the possible synergistic interaction between vitamins C and E to improve oxidative stress and catalytic and a regulatory role of Zn to antioxidant enzyme.
This intervention showed a remarkable significant success in detoxification of aluminium and improvement of the signs and symptoms of children with autism spectrum disorder as reflected by CARS after supplements as the current study revealed that, CARS score were improved after antioxidant supplements. There were no severe cases, 44.3% of children had moderate score and 55.7% had mild score.