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BMC Neurology
Published in: BMC Neurology 1/2011

Open Access 01-12-2011 | Research article

Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia

Authors: Yusra A Al-Yafee, Laila Y Al- Ayadhi, Samina H Haq, Afaf K El-Ansary

Published in: BMC Neurology | Issue 1/2011

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Abstract

Background

Xenobiotics are neurotoxins that dramatically alter the health of the child. In addition, an inefficient detoxification system leads to oxidative stress, gut dysbiosis, and immune dysfunction. The consensus among physicians who treat autism with a biomedical approach is that those on the spectrum are burdened with oxidative stress and immune problems. In a trial to understand the role of detoxification in the etiology of autism, selected parameters related to sulfur-dependent detoxification mechanisms in plasma of autistic children from Saudi Arabia will be investigated compared to control subjects.

Methods

20 males autistic children aged 3-15 years and 20 age and gender matching healthy children as control group were included in this study. Levels of reduced glutathione (GSH), total (GSH+GSSG), glutathione status (GSH/GSSG), glutathione reductase (GR), glutathione- s-transferase (GST), thioredoxin (Trx), thioredoxin reductase (TrxR) and peroxidoxins (Prxs I and III) were determined.

Results

Reduced glutathione, total glutathione, GSH/GSSG and activity levels of GST were significantly lower, GR shows non-significant differences, while, Trx, TrxR and both Prx I and III recorded a remarkably higher values in autistics compared to control subjects.

Conclusion

The impaired glutathione status together with the elevated Trx and TrxR and the remarkable over expression of both Prx I and Prx III, could be used as diagnostic biomarkers of autism.
Appendix
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Literature
1.
Eigsti IM, Shapiro T: A systems neuroscience approach to autism: biological, cognitive, and clinical perspectives. Ment Retard Dev Disabil Res Rev. 2003, 9: 205-15.CrossRefPubMed
2.
BMJ 328:226 doi: 10.1136/bmj.328.7433.226-c (published 22 January 2004)
3.
White JF: Intestinal pathophysiology in autism. Exp Biol Med. 2003, 228: 639-49.
4.
Buie T, Campbell DB, Fuchs GJ, Furuta GT, Levy J, Vandewater J, et al: Evaluation, diagnosis, and treatment of gastrointestinal disorders in individuals with ASDs: A consensus report. Pediatrics. 2010, 125 (Suppl 1): S1-S18.CrossRefPubMed
5.
Sweeten TL, Bowyer SL, Posey DJ, Halberstadt CM, McDougle CJ: Increased prevalence of familial autoimmunity in probands with pervasive developmental disorders. Pediatrics. 2003, 112: 420-10.1542/peds.112.5.e420.CrossRef
6.
Bolte S, Poustka F: The relation between general cognitive level and adaptive behavior domains in individuals with autism with and without co-morbid mental retardation. Child Psychiatry Hum Dev. 2002, 33: 165-72. 10.1023/A:1020734325815.CrossRefPubMed
7.
Golse B, Debray-Ritzen P, Durosay P, Puget K, Michelson AM: Alterations in two enzymes: superoxide dismutase and glutathione peroxidase in developmental infantile psychosis (infantile autism). Rev Neurol (Paris). 1978, 134: 699-705.
8.
Sogut S, Zoroglu SS, Ozyurt H, Yilmaz HR, Ozugurlu F, Sivasli E: Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clin Chim Acta. 2003, 331: 111-7. 10.1016/S0009-8981(03)00119-0.CrossRefPubMed
9.
Yorbik O, Sayal A, Akay C, Akbiyik DI, Sohmen T: Investigation of antioxidant enzymes in children with autistic disorder. Prostaglandins Leukot Essent Fatty Acids. 2002, 67: 341-3. 10.1054/plef.2002.0439.CrossRefPubMed
10.
Zoroglu SS, Armutcu F, Ozen S, Gurel A, Sivasli E, Yetkin O, et al: Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci. 2004, 254: 143-7.CrossRefPubMed
11.
Al-Gadani Y, Al-Ansary A, Al-Attas O, Al-Ayadhi L: Oxidative stress and antioxidant status in Saudi autistic children. Clin. Biochemistry. 2009, 24: 1032-1040.CrossRef
12.
James SJ, Cutler P, Melnyk S, Jernigan S, Janak L, Gaylor DW, et al: Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism. Am J Clin Nutr. 2004, 80: 1611-7.PubMed
13.
Al-Mosalem O, Al-Ansary A, Al-Attas O, Al-Ayadhi L: Metabolic biomarkers related to energy metabolism in Saudi autistic children. Clin Biochem. 2009, 42: 949-957. 10.1016/j.clinbiochem.2009.04.006.CrossRefPubMed
14.
Minshew NJ, Goldstein G, Dombrowski SM, Panchalingam K, Pettegrew JW: A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry. 1993, 33: 762-73. 10.1016/0006-3223(93)90017-8.CrossRefPubMed
15.
Minshew NJ, Goldstein G, Dombrowski SM, Panchalingam K, Pettegrew JW: A preliminary 31P MRS study of autism: evidence for undersynthesis and increased degradation of brain membranes. Biol Psychiatry. 1993, 33: 762-73. 10.1016/0006-3223(93)90017-8.CrossRefPubMed
16.
Chugani D, Sundram B, Behen M, Lee M, Moore G: Evidence of altered energy metabolism in autistic children, Prog. Neuropsychopharmacol Biol Psychiatry. 1999, 23: 635-641. 10.1016/S0278-5846(99)00022-6.CrossRef
17.
Moreno H, Borjas L, Arrieta A, Saez L, Prassad A, Estevez J, et al: Clinical heterogeneity of the autistic syndrome: a study of 60 families. Invest Clin. 1992, 33: 13-31.PubMed
18.
Dolske MC, Spollen J, McKay S, Lancashire E, Tolbert L: A preliminary trial of ascorbic acid as supplemental therapy for autism. Prog Neuropsychopharmacol Biol Psychiatry. 1993, 17: 765-74. 10.1016/0278-5846(93)90058-Z.CrossRefPubMed
19.
Chez MG, Buchanan CP, Aimonovitch MC, Becker M, Schaefer K, Black C, et al: Double-blind, placebo-controlled study of L-carnosine supplementation in children with autistic spectrum disorders. J Child Neurol. 2002, 17: 833-7. 10.1177/08830738020170111501.CrossRefPubMed
20.
Ming X, Stein TP, Brimacombe M, Johnson WG, Lambert GH, Wagner GC: Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot Essent Fatty Acids. 2005, 73: 379-84. 10.1016/j.plefa.2005.06.002.CrossRefPubMed
21.
Montuschi P, Barnes PJ, Roberts LJ: Isoprostanes: markers and mediators of oxidative stress. FASEB J. 2004, 18: 1791-800. 10.1096/fj.04-2330rev.CrossRefPubMed
22.
Zoroglu SS, Yurekli M, Meram I, Sogut S, Tutkun H, Yetkin O, et al: Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell Biochem Funct. 2003, 21: 55-60. 10.1002/cbf.989.CrossRefPubMed
23.
Edelson SB, Cantor DS: The neurotoxic etiology of the autistic spectrum disorder: a replicative study. Toxicol Ind H. 2000, 16: 239-47.CrossRef
24.
25.
El-Ansary A, Al-Daihan S, Al-Dbass A, Al-Ayadhi L: Measurement of selected ions related to oxidative stress and energy metabolism in Saudi autistic children. Clin Biochem. 2010, 43 (1-2): 63-70. 10.1016/j.clinbiochem.2009.09.008.CrossRefPubMed
26.
El-Ansary AK, Ben Bacha AG, Al-Ayadhi LY: Plasma fatty acids as diagnostic markers in autistic patients from Saudi Arabia. Lipids Health Dis. 2011, 10 (1): 62.-10.1186/1476-511X-10-62.CrossRefPubMedPubMedCentral
27.
Bradley H, Gough A, Sokhi RS, Hassell A, Waring R, Emery P: Sulfate metabolism is abnormal in patients with rheumatoid arthritis. Confirmation by in vivo biochemical findings. J Rheumatol. 1994, 21: 1192-1 196.PubMed
28.
Spooner RJ, Delides A, Goldberg DM: Heat stability and kinetic properties of human serum glutathione reductase activity in various disease states. Biochem Med. 1981, 26 (2): 239-48. 10.1016/0006-2944(81)90051-X.CrossRefPubMed
29.
Singh VK, Warren RP, Odell JD, et al: Antibodies to myelin basic protein in children with autistic behavior. Brain Behav Immun. 1993, 7: 97-103. 10.1006/brbi.1993.1010.CrossRefPubMed
30.
Singh VK: Plasma increase of interleukin-12 and interferon-gamma: Pathological significance in autism. Journal of Neuroimmunology. 1996, 66: 143-145. 10.1016/0165-5728(96)00014-8.CrossRefPubMed
31.
Molloy CA, Morrow AL, Meinzen-Derr J, Schleifer K, Dienger K, Manning-Courtney P, Altaye M, Wills-Karp M: Elevated cytokine levels in children with autism spectrum disorder. Journal of Neuroimmunology. 2006, 172: 198-205. 10.1016/j.jneuroim.2005.11.007.CrossRefPubMed
32.
Schafer FQ, Buettner GR: Redox environment of the cell as viewed through the redox state of the glutathione disulfide/glutathione couple. Free Radic Biol Med. 2001, 30 (11): 1191-212. 10.1016/S0891-5849(01)00480-4.CrossRefPubMed
33.
Chugani DC, Sundram BS, Behen M, Lee ML, Moore GJ: Evidence of altered energy metabolism in autistic children. Prog Neuropsychopharmacol Biol Psychiatry. 1999, 23: 635-41. 10.1016/S0278-5846(99)00022-6.CrossRefPubMed
34.
Klatt P, Lamas S: Regulation of protein function by S-glutathiolation in response to oxidative and nitrosative stress. Eur J Biochem. 2000, 267 (16): 4928-44.CrossRefPubMed
35.
Ji L, Liu R, Zhang XD, Chen HL, Bai H, Wang X, Zhao HL, Liang X, Hai CX: N-acetylcysteine attenuates phosgene-induced acute lung injury via up-regulation of Nrf2 expression. Inhal Toxicol. 2010, 22 (7): 535-42. 10.3109/08958370903525183.CrossRefPubMed
36.
Sagrista ML, Garcia AF, Africa De Madariaga M, Mora M: Antioxidant and pro oxidant effect of the thiolic compounds N-acetyl-L-cysteine and glutathione against free radical-induced lipid peroxidation. Free Radical Research. 2002, 36: 329-340. 10.1080/10715760290019354.CrossRefPubMed
37.
Deplancke B, Gaskins HR: Redox control of the transsulfuration and glutathione biosynthesis pathways. Current Opinion in Clinical Nutrition and Metabolic Care. 2002, 5: 85-92. 10.1097/00075197-200201000-00015.CrossRefPubMed
38.
Pastore A, Federici G, Bertini E, Piemonte E: Analysis of glutathione: Implication in redox and detoxification. Clinica Chimica Acta. 2003, 333: 19-39. 10.1016/S0009-8981(03)00200-6.CrossRef
39.
Hall AG: The role of glutathione in the regulation of apoptosis. European Journal of Clinical Investigation. 1999, 29: 238-245. 10.1046/j.1365-2362.1999.00447.x.CrossRefPubMed
40.
Geier DA, Ken JK, Graver CR, Adams JB: Biomarkers of environmental toxicity and susceptibility in autism. Neural Sci. 2008, 6: 431-561.
41.
Vojdani A, Bock K, Hirani AK: Low natural killer cell cytotoxic activity in autism: the role of glutathion, IL-2 and IL-15. J Neuroimmunal. 2008, 205: 148-154. 10.1016/j.jneuroim.2008.09.005.CrossRef
42.
Viña J, Sastre J, Pallardó F, Borrás C: Mitochondrial theory of aging: importance to explain why females live longer than males. Antioxid Redox Signal. 2003, 5 (5): 549-56. 10.1089/152308603770310194.CrossRefPubMed
43.
Palmieri L, Persico AM: Mitochondrial dysfunction in autism spectrum disorders: Cause or effect?. Biochimica et Biophysica Acta (BBA) - Bioenergetics. 2010, 1797 (6-7): 1130-1137. 10.1016/j.bbabio.2010.04.018.CrossRef
44.
Mutter J, Naumann J, Schneider R, Walach H, Haley B: Mercury and autism: accelerating evidence?. Neuroendocrinology Letters. 2004, 26: 439-446.
45.
Hung RG, Boffetta P, Brennan C, Malaveille A, Donato F: GST, NAT, SULT1A1, CYP1B1 genetic polymorphisms, interactions with environmental exposures and bladder cancer risk in a high-risk population. Int J Cancer. 2004, 110: 4598-4604.
46.
Buyske S, Williams TA, Mars AE, Stenroos ES, Ming SX, Wang R, Sreenath M, Factura MF, Reddy C, Lambert GH, Johnson WG: Analysis of case-parent trios at a locus with a deletion allele: association of GSTM1 with autism. BMC Genet. 2006, 10: 8-CrossRef
47.
James SJ, Melnyk S, Jernigan S, Cleves MA, Halsted CH, Wong DH, Cutler P, Bock K, Boris M, Bradstreet JJ, Baker SM, Gaylor DW: Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism. Am J Med Genet B Neuropsychiatr Genet. 2006, 141: 947-956.CrossRef
48.
Watson WH, Pohl J, Montfort WR, Stuchlik O, Reed MS, Powis G, Jones DP: Redox potential of human thioredoxin 1 and identification of a second dithiol/disulfide motif.''. J Biol Chem. 2003, 33408-33415. 278
49.
Lillig CH, Holmgren A: Thioredoxin and related molecules-from biology to health and disease. Antioxid Redox Signal. 2007, 9: 25-47. 10.1089/ars.2007.9.25.CrossRefPubMed
50.
Masutani H, et al: Thioredoxin as a neurotrophic cofactor and an important regulator of neuroprotection. Mol Neurobiol. 2004, 29: 229-242. 10.1385/MN:29:3:229.CrossRefPubMed
51.
Drechsel DA, Patel M: Respiration-dependent H2O2 removal in brain mitochondria via the thioredoxin/peroxiredoxin system. J Biol Chem. 2010, 285 (36): 27850-8. 10.1074/jbc.M110.101196.CrossRefPubMedPubMedCentral
52.
Rhee SG, Chae HZ, Kim K: Peroxiredoxins: a historical overview and speculative preview of novel mechanisms and emerging concepts in cell signaling. Free Rad Biol Med. 2005, 38: 1543-1552. 10.1016/j.freeradbiomed.2005.02.026.CrossRefPubMed
53.
Nonn L, Berggren M, Powis G: Increased Expression of Mitochondrial Peroxiredoxin-3(Thioredoxin Peroxidase-2) Protects Cancer Cells Against Hypoxia and Drug-Induced Hydrogen Peroxide-Dependent Apoptosis. Molecular Cancer Research. 2003, 682-689. 1
54.
Yavuz BB, Yavuz B, Halil M, Cankurtaran M, Ulger Z, Cankurtaran ES, et al: Serum elevated gamma glutamyltransferase levels may be a marker for oxidative stress in Alzheimer's disease. Int Psychogeriatr. 2008, 20: 815-23.CrossRefPubMed
55.
Spencer JPE, Jenner P, Halliwell B: Superoxide-dependent depletion of reduced glutathione by L-DOPA and dopamine: relevance to Parkinson disease. NeuroReport. 1995, 6: 1480-1484. 10.1097/00001756-199507310-00004.CrossRefPubMed
56.
Atmaca M, Kuloglu M, Tezcan E, Ustundag B: Antioxidant enzyme and malondialdehyde levels in patients with social phobia. Psychiatry Research. 2008, 159: 95-100. 10.1016/j.psychres.2002.12.004.CrossRefPubMed
Metadata
Title
Novel metabolic biomarkers related to sulfur-dependent detoxification pathways in autistic patients of Saudi Arabia
Authors
Yusra A Al-Yafee
Laila Y Al- Ayadhi
Samina H Haq
Afaf K El-Ansary
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2011
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/1471-2377-11-139

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