Oxidative Stress in Autism |
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Formation of anti-oxidative compounds from cysteine and
methylation procedures involving folate. MS = B12 dependent methionine synthetase MAT=methionine adenosyltransfurase SAM=S-adenosyl-methionine SAH=S-adenosylhomocysteine AK=Adenosyl kinase CBS=B6 dependent cystathionine beta-synthase MTase=Methyl transfurase THF=tetrahydrofolate 5-CH3THF=5-methyl tetrahydrofolate SAHH=SAH hyrolase |
Current positionIt is difficult to realise that the human body is protected from oxidation of its tissues when we spent so much energy taking oxygen from the air. In Amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD) and Alzheimer’s disease (AD) there is an indication of oxidative stress, where molecules seem damaged due to the oxidative molecules that the body produces itself. However, quite reasonably it could be that damage takes place due to some other pathological process and the oxidation of the molecules becomes permitted as a result of this. I.e. the oxidative stress could be primary or secondary. In autism there appears to be evidence that the oxidative stress (i.e. an increased inability to prevent oxidation of tissue) comes first. Oxidative stress biomarkersAlthough under histopathology reactive oxidative species (ROS) can be shown it is more difficult to carry this out using blood or urine
OxidationThere is a standard range of oxidative processes that take place and prevented by physiological systems. See this to understand why the changes may be involved with other biochemistry seen in the body of the autistic child. |
Oxidative Stress: Review
Kern JK, Jones AM. Evidence of toxicity, oxidative stress, and neuronal insult in autism. J Toxicol Environ Health B Crit Rev. 2006 Nov-Dec;9(6):485-99. (a good review, but would tend to suggest that the oxidative stress came from the damage rather than the other way around. Also goes into glutathione and its chemical involvement).
McGinnis
WR. Oxidative stress in autism. Altern Ther Health Med. 2004 Nov-Dec;10(6):22-36 (he explains more easily why it should be
involved).
Chauhan A, Chauhan V. Oxidative stress in autism. Pathophysiology. 2006 Aug;13(3):171-81. (a recent review, but spending a lot of time looking at specific compounds in erythrocyte membranes that they had showed to be raised)
James SJ, Cutler P, Melnyk S, Jernigan S, Janak L,
Gaylor DW, Neubrander JA. Metabolic
biomarkers of increased oxidative stress and impaired methylation capacity in
children with autism. Am J Clin Nutr. 2004 Dec;80(6):1611-7 (this goes
through a chain of compounds in the methionine cycle, which depends on
B12. They found a decrease in
glutathione but a decrease (not significant) in homocysteine, which is used to
make it through a chain that requires B6.
The only compound in the cycle that seemed raised was
s-adenosylhomocysteine, which is used for methylation donor possibly elsewhere)
Akyol O, Zoroglu SS, Armutcu F, Sahin S, Gurel A. Nitric oxide as a physiopathological factor in neuropsychiatric disorders. In Vivo. 2004 May-Jun;18(3):377-90. (There is substantial and mounting evidence that subtle abnormalities of reactive oxygen species (ROS) and nitric oxide (NO) may underlie a wide range of neuropsychiatric disorders. NO has chemical properties that make it uniquely suitable as an intracellular and intercellular messenger. It is produced by the activity of nitric oxide synthases which are present in peripheral tissues and in neurons. On the other hand, NO is known to be an oxygen radical in the central and peripheral nervous systems. NO has been implicated in a number of physiological functions such as noradrenaline and dopamine releases, memory and learning and certain pathologies such as schizophrenia, bipolar disorder and major depression. There are plenty of other articles showing NO to be associated with the disease process but little proof that they are not secondary to other pathogenic processes)
Tsaluchidu S, Cocchi M, Tonello L, Puri BK. Fatty acids and oxidative stress in psychiatric disorders. BMC Psychiatry. 2008 Apr 17;8 Suppl 1:S5. (this makes it clear that many of the psychiatry and mental problems have oxidative stress published data…and so autism should not be looked on as a condition on its own in this respect, but that the oxidation is secondary to the other aspects of the disease)
How environmental and genetic factors combine to cause
autism: A redox/methylation hypothesis. Deth R, Muratore C, Benzecry
J,
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Blood and urine biochemistry
Ming X, Stein TP, Brimacombe WG t al. Increased excretion of a lipid peroxidation biomarker in autism. Prostaglandins Leukot. Essent Fatty Acids 2005;73:379-84. (We evaluated children with autism for the presence of two oxidative stress biomarkers. Urinary excretion of 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-isoprostane-F2alpha (8-iso-PGF2alpha) were determined in 33 children with autism and 29 healthy controls. 8-iso-PGF2alpha levels were significantly higher in children with autism. The majority of autistic subjects showed a moderate increase in isoprostane levels while a smaller group of autistic children showed dramatic increases in their isoprostane levels. There was a trend of an increase in 8-OHdG levels in children with autism but it did not reach statistical significance. This basically showed that it was not a reliable diagnostic test but it could be used for other factors and for assessing treatment in certain patients)
Sweeten TL, Posey DL, Shankar S, McDougle
CJ. High nitric
oxide production in autistic distorder: a possible role for
interferon-gamma. Biol. Phych
2004:55;434-437.
Paşca
SP, Nemeş
B, Vlase
L, Gagyi
CE, Dronca
E, Miu
AC, Dronca
M. High levels of homocysteine and low serum paraoxonase 1 arylesterase
activity in children with autism. Life Sci. 2006
Apr 4;78(19):2244-8. (and low glutathione peroxidase) in serum. These were taken as indicators of oxidative
stress).
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 Dec 5;141(8):947-56. (plasma S-adenosyl methionine to S-adenosylhomocysteine is
an indicator of methylation capacity and were significantly decreased in
autistics.)
Zoroğlu SS, Yürekli M, Meram I, Söğüt S, Tutkun H, Yetkin O, Sivasli E, Savaş HA, Yanik M, Herken H, Akyol O. Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell Biochem Funct. 2003 Mar;21(1):55-60. (nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31).)
Adams et al. found that DMSA treatment (chelation of
metals) resulted in a great improvement or normalization of RBC (red blood
cell) levels of glutathione after just 1 round (3 days) of DMSA treatment, with
benefits lasting at least 1-2 months
Chauhan V, Chauhan A, Cohen IL, Brown WT, Sheikh A. Alteration in amino-glycerophospholipids levels in the plasma of children with autism: a potential biochemical diagnostic marker. Life Sci. 2004 Feb 13;74(13):1635-43. (observed that levels of phosphatidylethanolamine (PE) were decreased while phosphatidylserine (PS) were increased in the erythrocyte membranes of children with autism as compared to their non-autistic developmentally normal siblings). How this fits in it unclear
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 Oct 8;75(21):2539-49. (Lipid peroxidation was found to be elevated in autism indicating that oxidative stress is increased in this disease. Levels of major antioxidant proteins namely, transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein) in the serum, were significantly reduced in autistic children as compared to their developmentally normal non-autistic siblings. A striking correlation was observed between reduced levels of these proteins and loss of previously acquired language skills in children with autism. These results indicate altered regulation of transferrin and ceruloplasmin in autistic children who lose acquired language skills. It is suggested that such changes may lead to abnormal iron and copper metabolism in autism, and that increased oxidative stress may have pathological role in autism. More statistics are required but this is the sort of data that would be extremely useful for all studies involving treatments and assessments)
Söğüt S, Zoroğlu SS, Ozyurt H, Yilmaz HR, Ozuğurlu F, Sivasli E, Yetkin O, Yanik M, Tutkun H, Savaş HA, Tarakçioğlu M, Akyol O. Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism.Clin Chim Acta. 2003 May;331(1-2):111-7. (little data)
Zoroglu SS, Armutcu F, Ozen S, et al. Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. Eur Arch Psychiatry Clin Neurosci. 2004;254:143-147. (In the autistic group, increased thiobarbaric acid reactive substance levels (p < 0.001) and xanthine oxidase activity (p < 0.001) and SOD activity (p < 0.001), decreased catalase (p < 0.001) activity and unchanged adenosine demaminase activity were detected. They take this to suggest oxidative stress and processes taking place). This is an important finding.
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;67:341-343. (Activities of erythrocyte SOD, erythrocyte and plasma glutathione peroxidase in autistic children were significantly lower than normals, but glutathione levels were not)
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;75:2539-2549.
Zoroğlu SS, Yürekli M, Meram I, Söğüt S, Tutkun H, Yetkin O, Sivasli E, Savaş HA, Yanik M, Herken H, Akyol O. Pathophysiological role of nitric oxide and adrenomedullin in autism. Cell Biochem Funct. 2003 Mar;21(1):55-60. (nitric oxide (NO) is involved in the aetiopathogenesis of many neuropsychiatric disorders such as schizophrenia, bipolar disorder, depression, Alzheimer's disease, Hungtington disease and stroke. Although it has not been investigated yet, several recent studies proposed that NO may have a pathophysiological role in autism. Adrenomedullin (AM), a recently discovered 52-amino acid peptide hormone, induces vasorelaxation by activating adenylate cyclase and also by stimulating NO release. AM immune reactivity is present in the brain consistent with a role as a neurotransmitter. It has been stated that NO and AM do function in the regulation of many neurodevelopmental processes. The mean values of plasma total nitrite and AM levels in the autistic group were significantly higher than control values, respectively (p < 0.001, p = 0.028). There is no correlation between total nitrite and AM levels (r = 0.11, p = 0.31).)
Golse
B, Debray-Ritzen P, Durosay P, Puget K, Michelson AM. [Alterations in two enzymes: superoxide dismutase and glutathion peroxidase in
developmental infantile psychosis (infantile autism) (author's transl)] Rev
Neurol (
Sera from children with autism alter proliferation of
human neuronal progenitor cells exposed to oxidation. Mazur-Kolecka
B, Cohen IL, Jenkins EC, Flory M, Merz G, Ted Brown W, Frackowiak J. Neurotox Res. 2009 Jul;16(1):87-95. The specific genetic background that alters
vulnerability to some environmental insults has been suggested in the etiology
of autism; however, the specific pathomechanisms have not been identified.
Recently, we showed that sera from children with autism alter the maturation of
human neuronal progenitor cells (NPCs) in culture. We found that mild oxidative stress reduced
proliferation of differentiating NPCs but not immature NPCs. This decrease of
proliferation was less prominent in cultures treated with sera from children
with autism than from age-matched controls. These results suggest that altered
response of NPCs to oxidative stress may play a role in the etiology of
autism.
Plasma concentrations of selected antioxidants in
autistic children and adolescents. Krajcovicova-Kudlackova M,
Valachovicova M, Mislanova C, Hudecova Z, Sustrova M, Ostatnikova D. Bratisl Lek Listy. 2009;110(4):247-50. The results of previous studies have shown
that endogenous antioxidant defence is insufficient, indicating that exogenous
antioxidant could play a crucial role for oxidative stress prevention in
autism. Plasma concentrations of vitamins C, E, A,
carotenoids beta-carotene and lycopene were measured in 51 subjects with
autistic spectrum disorders aged 5-18 years (27 children aged 5-10 years, 24
subjects aged 11-18 years). The others
were similar in the control group.
Metabolic biomarkers related to energy metabolism in
Saudi autistic children. Al-Mosalem OA, El-Ansary A, Attas O,
Al-Ayadhi L. Clin Biochem. 2009
Jul;42(10-11):949-57. The obtained data
recorded 148.77% and 72.35% higher activities of Na(+)/K(+)ATPase and
cytokinase respectively in autistic patients which prove the impairment of
energy metabolism in these children compared to age and sex matching healthy
controls. This was done by looking at
the way in which different groups went about producing ATP, AMP, ADP and the
NADP forms of energy. This clearly was
hard work. The data was obtained from
the blood of the autistic cases and controls.
Increase in Cerebellar Neurotrophin-3 and Oxidative
Stress Markers in Autism. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Cerebellum. 2009 Apr 9
They looked for oxidative damage in the autistic cerebellum by measuring
8-hydroxydeoxyguanosine (8-OH-dG), a marker of DNA modification, in a subset of
cases analyzed for 3-NT. We also explored the hypothesis that oxidative damage
in autism is associated with altered expression of brain neurotrophins critical
for normal brain growth and differentiation.
Cerebellar 8-OH-dG showed trend towards higher levels with the increase
of 63.4% observed in autism. Analysis of
cerebellar NT-3 showed a significant (p = 0.034) increase (40.3%) in autism.
Furthermore, there was a significant positive correlation between cerebellar NT-3
and 3-NT (r = 0.83; p = 0.0408). 3-nitrotyrosine (3-NT) is a marker for oxidative
stress.
Cellular and mitochondrial glutathione redox imbalance in
lymphoblastoid cells derived from children with autism. James SJ,
Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, Gaylor DW. FASEB J. 2009 Aug;23(8):2374-83. Plasma biomarkers of oxidative stress have
been reported in autistic children; however, intracellular redox status has not
yet been evaluated. Lymphoblastoid cells (LCLs) derived from autistic children
and unaffected controls were used to assess relative concentrations of reduced glutathione (GSH) and oxidized disulfide glutathione (GSSG)
in cell extracts and isolated mitochondria as a measure of intracellular redox
capacity. The results indicated that the GSH/GSSG redox ratio was decreased and
percentage oxidized glutathione increased in both cytosol and mitochondria in
the autism LCLs. They then exposed the
cells to oxidative stress: using via the
sulfhydryl reagent thimerosal resulted in a greater decrease in the GSH/GSSG
ratio and increase in free radical generation in autism compared to control
cells. Acute exposure to physiological levels of nitric oxide decreased
mitochondrial membrane potential to a greater extent in the autism LCLs,
although GSH/GSSG and ATP concentrations were similarly decreased in both cell
lines. These results suggest that the
autism LCLs exhibit a reduced glutathione reserve capacity in both cytosol and
mitochondria that may compromise antioxidant defense and detoxification
capacity under prooxidant conditions.
Genetic variant of glutathione peroxidase 1 in autism.
Ming X, Johnson WG, Stenroos ES, Mars A, Lambert GH, Buyske S. Brain Dev. 2009 Feb 3.
An interesting sign that it is the oxidase problems that might come
first to create neurological damage.
Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. James SJ, Melnyk S, Fuchs G, Reid T, Jernigan S, Pavliv O, Hubanks A, Gaylor DW. Am J Clin Nutr. 2009 Jan;89(1):425-30. This is well discussed under the B12 section and the sulphate section.
Abnormal Transmethylation/transsulfuration Metabolism and DNA Hypomethylation Among Parents of Children with Autism. James SJ, Melnyk S, Jernigan S, Hubanks A, Rose S, Gaylor DW. J Autism Dev Disord. 2008 Nov;38(10):1976.
A mathematical model of glutathione metabolism.
Reed MC, Thomas RL, Pavisic J, James SJ, Ulrich CM, Nijhout HF. Theor Biol Med Model. 2008 Apr 28;5:8. We show that the glutathione pools in hepatic
cells and in the blood are quite insensitive to fluctuations in amino acid
input and offer an explanation based on model predictions. In contrast, we show
that hepatic glutathione pools are highly sensitive to the level of oxidative
stress. The model also correctly
simulates the metabolic profile of autism when oxidative stress is
substantially increased and the adenosine concentration is raised.
Cellular and mitochondrial glutathione redox imbalance in
lymphoblastoid cells derived from children with autism. James SJ,
Rose S, Melnyk S, Jernigan S, Blossom S, Pavliv O, Gaylor DW. FASEB J. 2009 Aug;23(8):2374-83.
Low natural killer cell cytotoxic activity in autism: the
role of glutathione, IL-2 and IL-15. Vojdani A, Mumper E,
Granpeesheh D, Mielke L, Traver D, Bock K, Hirani K, Neubrander J, Woeller KN,
O'Hara N, Usman A, Schneider C, Hebroni F, Berookhim J, McCandless J. J Neuroimmunol. 2008 Dec 15;205(1-2):148-54. we
explored the measurement of NK cell activity in 1027 blood samples from
autistic children obtained from ten clinics and compared the results to 113
healthy controls. This counting of NK cells and the measurement of their lytic
activity enabled us to express the NK cell activity/100 cells. At the cutoff of
15-50 LU we found that NK cell activity was low in 41-81% of the patients from
the different clinics. Overall, after this correction factor, 45% of the
children with autism still exhibited low NK cell activity, correlating with the
intracellular level of glutathione. Finally, we cultured lymphocytes of
patients with low or high NK cell activity/cell with or without glutathione,
IL-2 and IL-15. The induction of NK cell activity by IL-2, IL-15 and
glutathione was more pronounced in a subgroup with very low NK cell activity.
We conclude that that 45% of a subgroup of children with autism suffers from
low NK cell activity, and that low intracellular levels of glutathione, IL-2
and IL-15 may be responsible.
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Histopathology
Elizabeth M. Sajdel-Sulkowska,
Boguslaw Lipinski, Herb Windom, Tapan Audhya and Woody McGinnis. Oxidative Stress in Autism: Elevated Cerebellar 3-nitrotyrosine Levels. American
Journal of Biochemistry and Biotechnology 4 (2): 73-84, 2008. (Increased levels by 68% . An increase in Hg but not statistically
significant)
Yao Y, Walsh WJ, McGinnis WR, Praticò D. Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol. 2006 Aug;63(8):1161-4. (this was done by looking for urinary molecules that were indicators of endothelial irritation: prostaglandin F, isoprostane, and a thromboxane B
Teresa A. Evans, Sandra L. Siedlak, Liang Lu, Xiaoming
Fu, Zeneng Wang, Woody R. McGinnis, Evelyn Fakhoury, Rudy J. Castellani, Stanley L. Hazen, William
J. Walsh, Allen T. Lewis, Robert G. Salomon, Mark A. Smith, George Perry and
Xiongwei Zhu. The Autistic Phenotype Exhibits a Remarkably
Localized Modification of Brain Protein by Products of Free Radical-Induced
Lipid Oxidation. American
Journal of Biotechnology and Biochemistry 4 (2): 61-72, 2008. (Oxidative damage has been documented in the
peripheral tissues of autism patients. In this study, we sought evidence of oxidative
injury in autistic brain. Carboxyethyl pyrrole (CEP) and iso[4]levuglandin
(iso[4]LG)E2-protein adducts, that are uniquely generated through peroxidation of
docosahexaenoate and arachidonate-containing lipids respectively, and heme
oxygenase-1 were detected immunocytochemically in cortical brain tissues and by
ELISA in blood plasma. Significant immunoreactivity toward all three of these
markers of oxidative damage in the white matter and often extending well into
the grey matter of axons was found in every case of autism examined. This
striking threadlike pattern appears to be a hallmark of the autistic brain as
it was not seen in any control brain, young or aged, used as controls for the
oxidative assays. This is an important
finding in that they did the experiments and did them with controls who they
tried to have as dying of similar diseases.
The finding was that in autism were specifically different. The references in this article are up to date
as a review)
Increase in Cerebellar Neurotrophin-3 and Oxidative
Stress Markers in Autism. Sajdel-Sulkowska EM, Xu M, Koibuchi N. Cerebellum. 2009 Apr 9. Recently, we have reported an increase in
3-nitrotyrosine (3-NT), a marker of oxidative stress damage to proteins in
autistic cerebella. In the present study, we further explored oxidative damage
in the autistic cerebellum by measuring 8-hydroxydeoxyguanosine (8-OH-dG), a
marker of DNA modification, in a subset of cases analyzed for 3-NT. We also
explored the hypothesis that oxidative damage in autism is associated with
altered expression of brain neurotrophins critical for normal brain growth and
differentiation. The content of 8-OH-dG in cerebellar DNA isolated by the
proteinase K method was measured using an enzyme-linked immunosorbent assay
(ELISA); neurotrophin-3 (NT-3) levels in cerebellar homogenates were measured
using NT-3 ELISA. Cerebellar 8-OH-dG showed trend towards higher levels with
the increase of 63.4% observed in autism.
Activation/oxidation of vascular endothelium
Yao Y, Walsh WJ, McGinnis WR, Praticò D. Altered vascular phenotype in autism: correlation with oxidative stress. Arch Neurol. 2006 Aug;63(8):1161-4. (this was done by looking for urinary molecules that were indicators of endothelial irritation: prostaglandin F, isoprostane, and a thromboxane B
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Oxidative processes: physiology and pathology
The major cause of damage to cells results from
reactive oxygen species (ROS) – induced alterations of proteins and DNA. This comes about from the reactive
electrophilic oxidation products from polyunsaturated fatty acyls in membrane
lipids. Under normal conditions ROS are
cleared from the celll by the action of superoxide dismutase (SOD), catalase,
or glutathione peroxidase (GPx). SOD, as
MnSOD in the mitochondria and CuZnSOD in the cytoplasm removes superoxide anion
by converting it into hydrogen perodixe.
Catalase and CPx reduce this H2O2 to water. In the presence of unbound Cu, under certain
conditions SOD can promote oxidateive injury owing to a Cu catalyzed Haber-Weiss
reaction of H2O2 to generate –OH, a potent ROS.
Statistically significant elevations in ZnCuSOD were documented in
erythrocytes and in platelets of autistic individuals compared with controls (see above). This was
remarkably clear but could still not explain the actual cause of the oxidation
that was taking place. Glutathione is
looked on as a relatively useful molecule to stabilize the oxidative state of
proteins etc. Hence, the finding of low
levels of glutathione in plasma and acts
as a cofactor for the severely depressed levels of GPx (-44% in erythrocytes) an antioxidant enzyme,
is also indicative of oxidation taking place.
As a result, the H2O2 formed by the action of SOD would not be
efficiently removed owing to diminished levels of GPx. The imbalance is exacerbated by the low
plasma glutathione levels.
If you look at the biochemical pathways at the head of
the page, you can see that glutathione is formed from cysteine and this is
replaced from the diet or through homocysteine.
This cycle involved tetrahydrofolate and methylation systems. If there is simply too little ability to
produce this then the levels of glutathione will drop. Currently it is not all that clear if the
reason for the glutatione levels being low in red cells is because of lack of
production or it being used up in preventing oxidation. One factor showed that it was possible to
raise glutathione levels by treatment with B12 and cysteine. For information about its involvement in treatment.
This is to show how hydrogen peroxide is converted to water through the donation of hydrogen through glutathione and how other acyl donors can be similarly turned into hydroxyls by the same process.
Treatment: findings
MacFabe DF, Cain DP, Rodriguez-Capote K, Franklin AE, Hoffman JE, Boon F, Taylor AR, Kavaliers M, Ossenkopp KP. Neurobiological effects of intraventricular propionic acid in rats: possible role of short chain fatty acids on the pathogenesis and characteristics of autism spectrum disorders. Behav Brain Res. 2007 Jan 10;176(1):149-69. (purely showing that some dietary factor may show toxicity through oxidative stress and may produce pseudo autistic effects)
Dolske MC, Spollen J, McKay S,
Rossignol DA, Rossignol LW, James SJ, Melnyk S, Mumper E. The effects of hyperbaric oxygen therapy on oxidative stress, inflammation, and symptoms in children with autism: an open-label pilot study. BMC Pediatr. 2007 Nov 16;7:36. (this is mainly to show that hyperbaric oxygen may be adequately safe and shows no results in terms of treatment currently)
Oxidative stress in gut wall of inflammatory
bowel disease
At this point we don’t have the data for this in autism and the gut changes that might be expected. The literature is quite wide for other forms of IBD.
Aw TY. intestinal glutathione: determinant of mucosal peroxide transport, metabolism, and oxidative susceptibility. Toxicol Appl Pharmacol. 2005 May 1;204(3):320-8. Review.
Tsunada S, Iwakiri R, Ootani H, Aw TY, Fujimoto K. Redox imbalance in the colonic mucosa of ulcerative colitis. Scand J Gastroenterol. 2003 Sep;38(9):1002-3.
Sido B, Seel C, Hochlehnert A, Breitkreutz R, Dröge W. Low intestinal glutamine level and low glutaminase activity in Crohn's disease: a rational for glutamine supplementation? Dig Dis Sci. 2006 Dec;51(12):2170-9. Epub 2006 Nov
Sido B, Hack V, Hochlehnert A, Lipps H, Herfarth C, Dröge W. Impairment of intestinal glutathione synthesis in patients with inflammatory bowel disease. Gut. 1998 Apr;42(4):485-92.
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