International Journal of Nutrition, Pharmacology, Neurological Diseases

ORIGINAL ARTICLE
Year
: 2012  |  Volume : 2  |  Issue : 1  |  Page : 53--56

Reduced levels of antioxidant proteins in children with autism in Oman


Musthafa M Essa1, Gilles J Guillemin2, Mostafa I Waly3, Marwan M Al-Sharbati4, Yahya M Al-Farsi4, Faruck L Hakkim3, Amanat Ali3, Mohammed A Al-Shafaee4,  
1 Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman; Neuropharmacology Group, Department of Pharmacology, School of Medical Science, University of New South Wales, Sydney, Australia
2 Neuropharmacology Group, Department of Pharmacology, School of Medical Science, University of New South Wales, Sydney, Australia
3 Department of Food Science and Nutrition, College of Agriculture and Marine Sciences, Sultan Qaboos University, Oman
4 Department of Food Science and Nutrition, College of Medicine and Health Sciences, Sultan Qaboos University, Oman

Correspondence Address:
Musthafa M Essa
Department of Food Sciences and Nutrition, CAMS, Sultan Qaboos University, PO No: 34, Al-Khoud, Muscat, Postal Code: 123, Sultanate of Oman

Abstract

Background: Autism spectrum disorder (ASD) is a severe neuro-developmental disorder with poorly understood etiology. Numerous studies evidenced that oxidative stress and altered antioxidant status could be involved in the pathophysiology of ASD. It is also reported that the altered levels of antioxidant proteins such as ceruloplasmin (copper-binding protein) and transferrin (iron-binding protein) could enhance the oxidative stress directly or indirectly and it can considerably retard acquired language skills in autistic children. But these types of studies in children with autism in Oman were not available. Materials and Methods: To reveal this paradigm, in this study, we evaluated the plasma levels of ceruloplasmin and transferrin in Omani autistic children and compared the results with age matched control children (n = 20). Results: In accordance with the previous reports, significantly lower plasma levels of ceruloplasmin and of transferrin were observed in Omani autistic children as compared to normal children. Conclusion: This suggests that such changes may lead to abnormalities of iron and copper metabolism, resulting in the enhancement of the oxidative stress and contributing to the pathogenesis of ASD. However, the underlying mechanism is still unclear and further extensive studies are warranted.



How to cite this article:
Essa MM, Guillemin GJ, Waly MI, Al-Sharbati MM, Al-Farsi YM, Hakkim FL, Ali A, Al-Shafaee MA. Reduced levels of antioxidant proteins in children with autism in Oman.Int J Nutr Pharmacol Neurol Dis 2012;2:53-56


How to cite this URL:
Essa MM, Guillemin GJ, Waly MI, Al-Sharbati MM, Al-Farsi YM, Hakkim FL, Ali A, Al-Shafaee MA. Reduced levels of antioxidant proteins in children with autism in Oman. Int J Nutr Pharmacol Neurol Dis [serial online] 2012 [cited 2021 Jun 14 ];2:53-56
Available from: https://www.ijnpnd.com/text.asp?2012/2/1/53/93136


Full Text

 Introduction



Autism spectrum disorder (ASD) is characterized by severe impairment in social interaction and communication and by the presence of stereotyped pattern of behaviors. It is a pervasive developmental disorder that is influenced by environmental, genetic, and immunological factors. [1],[2],[3] ASD occurs in early childhood and also affects more males than females, occurring at a ratio of 4:1. [4] The identification of specific biochemical marker with relevance to pathogenesis of ASD might increase reliability of behavioral diagnosis of this disorder. Ceruloplasmin and transferrin are the major antioxidant proteins that are synthesized in several tissues including brain. Ceruloplasmin is a copper-binding α-serum glycoprotein that transports 95% of copper in blood and it is involved in the metabolism of copper to which it binds reversibly. [5] It also acts as ferroxidase and super oxide dismutase, and it protects polyunsaturated fatty acids in red blood cell membranes from active oxygen radicals. [6],[7] It has been reported that the lower levels of ceruloplasmin and transferrin are directly manifesting the state of ASD in children with loss of acquired language skills. [5]

The high prevalence of ASD among children in the Western industrialized countries has become a major alarming concern. [8] On the other hand, awareness of the prevalence of autism in the Arab world is still very limited and no concrete reports are available from this region. The Sultanate of Oman is a large country with an estimated population of 3.5 million. The prevalence estimate of ASD in Oman in the year 2011 was 1.4 per 10,000 children, which is comparatively low. [9] Previously, our group reported altered levels of plasma oxidative markers, [10] leptin, [11] and monoamine oxidase activities. [12] But no such data are available with relevance to levels of ceruloplasmin and transferrin of these autistic children, which may correlate with pathogenesis of ASD. In the present study, we tried to envisage the involvement of ceruloplasmin and transferrin in Omani children autistic children. To the best of our knowledge, this is the first report on the levels of ceruloplasmin and transferrin in Omani autistic children.

 Materials and Methods



Subjects

A total of 40 Omani children, between the age of 3 and 10 years, consisting of autistic (n = 20, 16 males and 4 females) and their age-matched normal children (n = 20, 11 males and 9 females) from 20 different families were recruited for this study. The autistic children were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) American Psychiatric Association, 2000. Ascertainment of ASD diagnosis was further supplemented by completing a standardized and validated Arabic version of the Childhood Autism Rating Scale (CARS) questionnaire. A written consent was obtained from the parents in each individual case, according to the guidelines of the Ethical Committee of Sultan Qaboos University (SQU), Oman (EC 158/2010).

Biochemical and data analysis

After an overnight fast, the blood samples from both the autistic and control children were collected at the SQU hospital and used for biochemical analysis. The levels of transferrin and ceruloplasmin were assessed by using commercially available kit . Data analysis was done by using the GraphPad Prism 5 software.

 Results



The plasma levels of ceruloplasmin and transferrin were significantly lower in autistic children than in age matched, non-autistic controls (n = 20). The measured values, expressed as the mean ± SD, were compared using unpaired Student's t-test; P < 0.01 was considered as significant.

 Discussion



Extensive studies have demonstrated that oxidative stress plays a vital role in the pathology of several neurological diseases such as Alzheimer disease, [13] Down syndrome, [14] Parkinson's disease, [15],[16] and schizophrenia, [17],[18] including autism. The exact mechanism of oxidative stress in ASD is still unclear. It may be due to increased production of pro-oxidants, and deficiencies of antioxidant enzymes and antioxidant proteins or both.

Copper (Cu), a trace metal, is an essential element for living cells. It plays an important role in redox reactions because of its easy conversion from Cu+ to Cu++. Copper is transported mainly by ceruloplasmin, a copper-binding antioxidant protein that is synthesized in several tissues, including brain. [19] Ceruloplasmin inhibits the peroxidation of membrane lipids catalyzed by metal ions, such as iron and copper. [20] Transferrin also acts as an antioxidant by reducing the concentration of free ferrous ion that catalyzes the conversion of hydrogen peroxide to highly toxic hydroxyl radical by Fenton reaction. In addition, Fe3+ protoporphyrin (heme) group is also present in the four protein subunits of catalase enzyme that plays a vital role in defense mechanism against damage by reactive oxygen species (ROS). [21] Catalase converts hydrogen peroxide to water and molecular oxygen, thereby reducing the amount of free hydroxyl radical formation. [21] It has been reported that the plasma levels of ceruloplasmin and transferrin in the patients with Alzheimer's and Parkinson's disease were lower than in their controls. [22],[16] Evidences are also available for higher iron concentration in the substantia nigra, which has been suggested to lead to increased lipid peroxidation and neuronal death in Parkinson's disease. [22],[23]

It has been reported that ceruloplasmin and transferrin are involved in maintaining the appropriate physiological concentration of ions such as copper and iron in the plasma, which eventually leads to reduction in ion imbalance induced oxidative stress in most of the neurodegenerative diseases. Probable role of ceruoplasmin and transferrin in ASD is not yet revealed. In this study, a significant (P < 0.01) reduction was observed in the ceruoplasmin and transferrin levels in plasma of Omani autistic children

[Figure 1]. This result is concomitant with that of Chauhan et al. [5] who reported lower levels of transferrin in 16 of 19 (84%) children with autism as compared to their unaffected siblings, whereas ceruloplasmin levels were lower in 13 of 19 (68%) children with autism as compared to their developmentally normal siblings in the USA. [5] Reduction in the levels of ceruloplasmin and transferrin in autistic children was directly correlated with loss of acquired language skills. [5] Since copper and ferrous iron contents are important to maintain the memory, their abnormal metabolism through altered levels of ceruloplasmin and transferrin may play a pathological role in autism with cognitive impairment. In fact, some preliminary studies have suggested altered serum Cu/Zn ratios in autism. [24] {Figure 1}

In conclusion, the results of this study show marked reduction in the levels of ceruloplasmin and transferrin in Omani autistic children, which is in agreement with previous reports. These antioxidant proteins may directly or indirectly regulate the antioxidant status in pathogenesis of autism. Thus, it is suggested that ceruloplasmin and transferrin levels strongly correlate with oxidative stress in the pathogenesis of autism and it can manifest the degree of autistic ratio in case-control based studies. However, the underlying mechanism is still unclear and further extensive studies are warranted.

 Acknowledgment



The project was supported by Sultan Qaboos University; Oman, in the form of internal grant is gratefully acknowledged (IG/AGR/FOOD/11/02). We would also like to thank the SQU Hospital staff and the parents of children with autism, as well as the normal children for their cooperation during this study.

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