Users Online: 238

Home Print this page Email this page Small font sizeDefault font sizeIncrease font size

Home | About us | Editorial board | Search | Ahead of print | Current issue | Archives | Submit article | Instructions | Subscribe | Contacts | Login 
     

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

Reduced levels of antioxidant proteins in children with autism in Oman


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

Date of Submission01-Jan-2012
Date of Acceptance01-Feb-2012
Date of Web Publication23-Feb-2012

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

Login to access the Email id

Source of Support: Sultan Qaboos University; Oman, in the form of internal grant is gratefully acknowledged (IG/AGR/FOOD/11/02)., Conflict of Interest: None


DOI: 10.4103/2231-0738.93136

Rights and Permissions
   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.

Keywords: Autism, ceruloplasmin, Omani children, oxidative stress, transferrin


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;2:53-6

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 2020 Nov 23];2:53-6. Available from: https://www.ijnpnd.com/text.asp?2012/2/1/53/93136


   Introduction Top


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 Top


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 Top


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 Top


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: Plasma levels of ceruloplasmin and transferrin in Omani autistic children population. The measured values, expressed as the mean ± SD (n = 20), were compared using unpaired Student's t-test; P < 0.01 was considered as significant

Click here to view


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 Top


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.

 
   References Top

1.Lord C, Cook EH, Leventhal BL, Amaral DG. Autism spectrum disorders. Neuron 2000;28:355-63.  Back to cited text no. 1
[PUBMED]  [FULLTEXT]  
2.Muhle R, Trentacost SV, Rapin K. The genetics of autism. Pediatrics 2004;113:486-4722.  Back to cited text no. 2
    
3.Micali N, Chakrabarti S, Fombonne E. The broad autism phenotype: Finding from an epidemiological survey. Autism 2004;8:21-37.  Back to cited text no. 3
[PUBMED]  [FULLTEXT]  
4.James JS, Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, et al. Cellular and mitochondrial glutathione redox imbalance in lymphoblastoid cells derived from children with autism. FASEB J 2009;23:2374-83.  Back to cited text no. 4
    
5.Chauhan A, Chauhan V, Brown WT, Cohen I. Oxidative stress in autism: Increased lipid peroxidation and reduced serum levels of ceruloplasmin and transferrin - the antioxidant proteins. Life Sci 2004;75:2539-49.  Back to cited text no. 5
[PUBMED]  [FULLTEXT]  
6.Sass-Kortsak A. Copper metabolism. Adv Clin Chem 1965;8:1-67.  Back to cited text no. 6
[PUBMED]    
7.Arnaud P, Gianazza E, Miribel L. Ceruloplasmin. Meth Enz 1988;163:441-52.   Back to cited text no. 7
    
8.Oliveira G, Diogo L, Grazina M, Garcia P, Ataíde A, Marques C, et al. Mitochondrial dysfunction in autism spectrum disorders: A population-based study. Dev Med Child Neur 2005;47:185-9.   Back to cited text no. 8
    
9.Al-Farsi YM, Al-Sharbati MM, Al-Farsi OA, Al-Shafaee MS, Brooks DR, Waly MI. Brief report: Prevalence of autistic spectrum disorders in the Sultanate of Oman. J Autism Dev Dis 2011;41:821-5.  Back to cited text no. 9
    
10.Essa MM, Guillemin GJ, Waly MI, Al-Sharbati MM, Al-Farsi YM, Hakkim FL, et al. Increased Markers of Oxidative Stress in Autistic Children of the Sultanate of Oman. Biol Trace Elem Res 2010 Nov 30.  Back to cited text no. 10
    
11.Essa MM, Braidy N, Al-Sharbati MM, Al-Farsi YM, Ali A, Waly MI, et al. Elevated Plasma Leptin Levels in Autistic Children of Sultanate of Oman. Int J Biol Med Res 2011a;2:803-5.  Back to cited text no. 11
    
12.Essa MM, Al-Sharbati MM, Al-Farsi YM, Ali A, Waly MI, Al-Shaffae MA, et al. Altered activities of monoamine oxidase A in Omani Autistic Children - A brief report. Int J Biol Med Res 2011b;2:811-3.  Back to cited text no. 12
    
13.Christen Y. Oxidative stress and Alzheimer's disease. Am J Clin Nutr 2000;71:621-9.  Back to cited text no. 13
    
14.Kannan K, Jain SK. Oxidative stress and apoptosis. Pathophy 2007;3:153-63.   Back to cited text no. 14
    
15.Bostantjopoulou S, Kyriazis G, Katsarou Z, Kiosseoglou G, Kazis A, Mentenopoulos G. Superoxide dismutase activity in early and advanced Parkinson's disease. Fun Neur 1997;12:63-8.   Back to cited text no. 15
    
16.Torsdottir G, Kristinsson J, Sveinbjornsdoltir S, Snaedal J, Johannesson T. Copper, ceruloplasmin, superoxide dismutase and iron parameters in Parkinson's disease. Pharm Toxicol 1999;85:239-43.   Back to cited text no. 16
    
17.Herken H, Uz E, Ozyurt H, Sogurt S, Virit O, Akyol O. Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Mol Psych 2001;6:66-73.  Back to cited text no. 17
    
18.Akyol O, Herken H, Uz E, Fadillioglu E, Unal S, Sogut S, et al. The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients. The possible role of oxidant/antioxidant imbalance. Prog Neuropsych Biol Psych 2002;26:995-1005.  Back to cited text no. 18
    
19.Vassiliev V, Harris ZL, Zatta P. Ceruloplasmin in neurodegenerative diseases. Brain Res Rev 2005;49:633-40.  Back to cited text no. 19
[PUBMED]  [FULLTEXT]  
20.Gutteridge JM. Antioxidant properties of ceruloplasmin towards iron- and copper-dependent oxygen radical formation. FEBS Lett 1983;157:37-40.  Back to cited text no. 20
[PUBMED]  [FULLTEXT]  
21.Chance B. Catalases and peroxidases, part II. Meth Biochem Anal 1954;1:408-24.  Back to cited text no. 21
    
22.Logroscino G, Marder K, Graziano J, Freyer G, Slavokovich V, LoIacono N, et a. Altered systemic iron metabolism in Parkinson's disease. Neuron 1997;49:714-7.  Back to cited text no. 22
    
23.Hirsch EC, Faucheux BA. Iron metabolism and Parkinson's disease. Movement Dis 1998;13:39-45.  Back to cited text no. 23
[PUBMED]    
24.McGinnis WR. Oxidative stress in autism. Altern Ther Health Med 2004;10:22-36.  Back to cited text no. 24
    


    Figures

  [Figure 1]


This article has been cited by
1 Assessment of malondialdehyde levels, superoxide dismutase, and catalase activity in children with autism spectrum disorders
Hatice Altun,Nilfer Sahin,Ergül Belge Kurutas,Umut Karaaslan,Feyza Hatice Sevgen,Ebru Findikli
Psychiatry and Clinical Psychopharmacology. 2018; : 1
[Pubmed] | [DOI]
2 Comparison of urinary oxidative biomarkers in Iranian children with autism
Akram Ranjbar,Vahid Rashedi,Mohammad Rezaei
Research in Developmental Disabilities. 2014; 35(11): 2751
[Pubmed] | [DOI]
3 Necrosis is increased in lymphoblastoid cell lines from children with autism compared with their non-autistic siblings under conditions of oxidative and nitrosative stress
P. A. E. Main,P. Thomas,A. Esterman,M. F. Fenech
Mutagenesis. 2013; 28(4): 475
[Pubmed] | [DOI]
4 Impaired antioxidant status and reduced energy metabolism in autistic children
M.M. Essa,N. Braidy,M.I. Waly,Y.M. Al-Farsi,M. Al-Sharbati,S. Subash,A. Amanat,M.A. Al-Shaffaee,G.J. Guillemin
Research in Autism Spectrum Disorders. 2013; 7(5): 557
[Pubmed] | [DOI]



 

Top
 
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Acknowledgment
    References
    Article Figures

 Article Access Statistics
    Viewed3230    
    Printed125    
    Emailed0    
    PDF Downloaded137    
    Comments [Add]    
    Cited by others 4    

Recommend this journal