Afaf El-Ansary

Metabolic biomarkers related to oxidative stress and antioxidant status in Saudi autistic children.

OBJECTIVE Measurement of oxidative stress and antioxidant-related parameters (enzymatic and non-enzymatic) in Saudi autistic children. DESIGN AND METHODS 30 autistic children (22 males and 8 females) aged 3-15 years (25/30 of these were below 8 years old), and 30 healthy children as control group were included in this study. Levels of lipid peroxides, vitamin E, vitamin C, glutathione together with enzymatic activities of glutathione peroxidase (GSH-Px), and catalase were determined in plasma while superoxide dismutase (SOD was measured in red blood cells of both groups. RESULTS Lipid peroxidation was found to be significantly higher in autistic compared to control Saudi children. On the other hand, vitamin E and glutathione were remarkably lower in autistic patients while vitamin C shows non-significant lower values. Regarding the enzymatic antioxidants, both glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) were significantly higher in autistic compared to control while catalase recorded more or less similar activities in both groups. CONCLUSION Saudi autistic children are under H(2)O(2) stress due to GSH depletion, over expression of SOD together with the unchanged catalase enzyme. This could be helpful in the early diagnosis of young autistic patients and suggesting the possibility of antioxidant supplementation for the early intervention with autistic children.

Etiology of autistic features: the persisting neurotoxic effects of propionic acid

BackgroundRecent clinical observations suggest that certain gut and dietary factors may transiently worsen symptoms in autism. Propionic acid (PA) is a short chain fatty acid and an important intermediate of cellular metabolism. Although PA has several beneficial biological effects, its accumulation is neurotoxic.MethodsTwo groups of young Western albino male rats weighing about 45 to 60 grams (approximately 21 days old) were used in the present study. The first group consisted of oral buffered PA-treated rats that were given a neurotoxic dose of 250 mg/kg body weight/day for three days, n = eight; the second group of rats were given only phosphate buffered saline and used as a control. Biochemical parameters representing oxidative stress, energy metabolism, neuroinflammation, neurotransmission, and apoptosis were investigated in brain homogenates of both groups.ResultsBiochemical analyses of brain homogenates from PA-treated rats showed an increase in oxidative stress markers (for example, lipid peroxidation), coupled with a decrease in glutathione (GSH) and glutathione peroxidase (GPX) and catalase activities. Impaired energy metabolism was ascertained through the decrease of lactate dehydrogenase and activation of creatine kinase (CK). Elevated IL-6, TNFα, IFNγ and heat shock protein 70 (HSP70) confirmed the neuroinflammatory effect of PA. Moreover, elevation of caspase3 and DNA fragmentation proved the pro-apoptotic and neurotoxic effect of PA to rat pupsConclusionBy comparing the results obtained with those from animal models of autism or with clinical data on the biochemical profile of autistic patients, this study showed that the neurotoxicity of PA as an environmental factor could play a central role in the etiology of autistic biochemical features.

GABAergic/glutamatergic imbalance relative to excessive neuroinflammation in autism spectrum disorders

BackgroundAutism spectrum disorder (ASD) is characterized by three core behavioral domains: social deficits, impaired communication, and repetitive behaviors. Glutamatergic/GABAergic imbalance has been found in various preclinical models of ASD. Additionally, autoimmunity immune dysfunction, and neuroinflammation are also considered as etiological mechanisms of this disorder. This study aimed to elucidate the relationship between glutamatergic/ GABAergic imbalance and neuroinflammation as two recently-discovered autism-related etiological mechanisms.MethodsTwenty autistic patients aged 3 to 15 years and 19 age- and gender-matched healthy controls were included in this study. The plasma levels of glutamate, GABA and glutamate/GABA ratio as markers of excitotoxicity together with TNF-α, IL-6, IFN-γ and IFI16 as markers of neuroinflammation were determined in both groups.ResultsAutistic patients exhibited glutamate excitotoxicity based on a much higher glutamate concentration in the autistic patients than in the control subjects. Unexpectedly higher GABA and lower glutamate/GABA levels were recorded in autistic patients compared to control subjects. TNF-α and IL-6 were significantly lower, whereas IFN-γ and IFI16 were remarkably higher in the autistic patients than in the control subjects.ConclusionMultiple regression analysis revealed associations between reduced GABA level, neuroinflammation and glutamate excitotoxicity. This study indicates that autism is a developmental synaptic disorder showing imbalance in GABAergic and glutamatergic synapses as a consequence of neuroinflammation.

Neuroinflammation in autism spectrum disorders

ObjectivesThe neurobiological basis for autism remains poorly understood. However, research suggests that environmentalfactors and neuroinflammation, as well as genetic factors, are contributors. This study aims to test the role that might be played by heat shock protein (HSP)70, transforming growth factor (TGF)-β2, Caspase 7 and interferon-γ (IFN-γ)in the pathophysiology of autism.Materials and methodsHSP70, TGF-β2, Caspase 7 and INF-γ as biochemical parameters related to inflammation were determined in plasma of 20 Saudi autistic male patients and compared to 19 age- and gender-matched control samples.ResultsThe obtained data recorded that Saudi autistic patients have remarkably higher plasma HSP70, TGF-β2, Caspase 7 and INF-γ compared to age and gender-matched controls. INF-γ recorded the highest (67.8%) while TGF-β recorded the lowest increase (49.04%). Receiver Operating Characteristics (ROC) analysis together with predictiveness diagrams proved that the measured parameters recorded satisfactory levels of specificity and sensitivity and all could be used as predictive biomarkers.ConclusionAlteration of the selected parameters confirm the role of neuroinflammation and apoptosis mechanisms in the etiology of autism together with the possibility of the use of HSP70, TGF-β2, Caspase 7 and INF-γ as predictive biomarkers that could be used to predict safety, efficacy of a specific suggested therapy or natural supplements, thereby providing guidance in selecting it for patients or tailoring its dose.

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

BackgroundXenobiotics 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.Methods20 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.ResultsReduced 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.ConclusionThe 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.

Identification of potential biomarkers of gold nanoparticle toxicity in rat brains

BackgroundGold nanoparticles (AuNPs) are finding increased use in therapeutics and imaging. However, their toxic effects still remain to be elucidated. Therefore this study was undertaken to study the biochemical effects of AuNPs on rat brain and identify potential biomarkers of AuNP toxicity.MethodsMale Wister rats weighing 150–200 g were injected with 20 μg/kg body weight of 20-nm gold nanoparticles for 3 days through the intraperitoneal route. The rats were killed by carbon dioxide asphyxiation 24 h after the last dose of gold nanoparticle injection. The parameters studied included lipid peroxidation, glutathione peroxidase, 8- hydroxydeoxyguanosine, caspase-3, heat shock protein70, serotonin, dopamine, gamma amino-butyric acid and interferon-γ.ResultsIn this study AuNPs caused generation of oxidative stress and a decrease of antioxidant enzyme, viz., glutathione peroxidase activity in rat brain. This was accompanied by an increase in 8-hydroxydeoxyguanosine, caspase-3 and heat shock protein70, which might lead to DNA damage and cell death. Gold nanoparticles also caused a significant decrease in the levels of neurotransmitters like dopamine and serotonin, indicating a possible change in the behavior of the treated animals. There was a significant increase in the cerebral levels of IFN-γ in treated animals.ConclusionThis study concludes that AuNPs cause generation of oxidative stress and an impairment of the antioxidant enzyme glutathione peroxidase in rat brain. AuNPs also cause generation of 8-hydroxydeoxyguanosine (8OHdG), caspase-3 and heat shock protein70 (Hsp70), and IFN-γ, which may lead to inflammation and DNA damage/cell death.

Plasma fatty acids as diagnostic markers in autistic patients from Saudi Arabia

BackgroundsAutism is a family of developmental disorders of unknown origin. The disorder is characterized by behavioral, developmental, neuropathological and sensory abnormalities, and is usually diagnosed between the ages of 2 and 10 with peak prevalence rates observed in children aged 5-8 years. Recently, there has been heightened interest in the role of plasma free fatty acids (FA) in the pathology of neurological disorders. The aim of this study is to compare plasma fatty acid profiles of Saudi autistic patients with those of age-matching control subjects in an attempt to clarify the role of FA in the etiology of autism.Methods26 autistic patients together with 26-age-matching controls were enrolled in the present study. Methyl esters of FA were extracted with hexane, and the fatty acid composition of the extract was analyzed on a gas chromatography.ResultsThe obtained data proved that fatty acids are altered in the plasma of autistic patients, specifically showing an increase in most of the saturated fatty acids except for propionic acid, and a decrease in most of polyunsaturated fatty acids. The altered fatty acid profile was discussed in relation to oxidative stress, mitochondrial dysfunction and the high lead (Pb) concentration previously reported in Saudi autistic patients. Statistical analysis of the obtained data shows that most of the measured fatty acids were significantly different in autistic patients compared to age -matching controls.ConclusionsReceiver Operating Characteristic (ROC) curve analysis shows satisfactory values of area under the curve (AUC) which could reflect the high degree of specificity and sensitivity of the altered fatty acids as biomarkers in autistic patients from Saudi Arabia.

Metabolic biomarkers related to energy metabolism in Saudi autistic children

OBJECTIVES Energy metabolism is usually manipulated in many neurodegenerative diseases. Autism is considered a definable systemic disorder resulting in a number of diverse factors that may affect the brain development and functions both pre and post natal. The increased prevalence of autism will have enormous future public implications and has stimulated intense research into potential etiologic factors. This study aims to establish a connection between autism and the deterioration accompanied it, especially in the brain cognitive areas through a postulation of energy manipulation. MATERIALS AND METHODS The biochemical changes in activities of enzymes and pathways that participate in the production of ATP as the most important high-energy compound needed by the human brain were measured in Saudi autistic children. Na(+)/K(+)ATPase, ectonucleotidases (NTPDases) (ADPase and ATPase) and creatine kinase (CK), were assessed in plasma of 30 Saudi autistic patients and compared to 30 age-matching control samples. In addition, adenosine mono, di and trinucleotides (ATP, ADP, and AMP) were measured calorimetrically in the red blood cells of both groups and the adenylate energy charge (AEC) was calculated. Moreover, lactate concentration in plasma of both groups was monitored. RESULTS The obtained data recorded 148.77% and 72.35% higher activities of Na(+)/K(+)ATPase and CK respectively in autistic patients which prove the impairment of energy metabolism in these children compared to age and sex matching healthy controls. While ADPase was significantly higher in autistic patients, ATPase were non-significantly elevated compared to control. In spite of the significant increase of Na(+)/K(+)ATPase activity in autistic patients, there was no significant difference in the levels of ATP, ADP, and AMP in both groups and the calculated AEC values were 0.814+/-0.094 and 0.806+/-0.081 for autistic and control groups respectively. The unchanged AEC value in autistic patients was easily correlated with the induced activity of CK and ADPase as two enzymes playing a critical role in the stabilization of AEC. Lactate as an important energy metabolite for the brain was significantly higher in autistic patients compared to control showing about 40% increase. CONCLUSION The present study confirmed the impairment of energy metabolism in Saudi autistic patients which could be correlated to the oxidative stress previously recorded in the same investigated samples. The identification of biochemical markers related to autism would be advantageous for earlier clinical diagnosis and intervention.

Impaired plasma phospholipids and relative amounts of essential polyunsaturated fatty acids in autistic patients from Saudi Arabia

BackgroundsAutism is a developmental disorder characterized by social and emotional deficits, language impairments and stereotyped behaviors that manifest in early postnatal life. This study aims to compare the relative concentrations of essential fatty acids (Linoleic and α- linolenic), their long chain polyunsaturated fatty acids and phospholipids in plasma of autistic patients from Saudi Arabia with age-matching controls.Methods25 autistic children aged 3-15 years and 16 healthy children as control group were included in this study. Relative concentration of essential fatty acids/long chain polyunsaturated fatty acids and omega-3/omega-6 fatty acid series together with phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine were measured in plasma of both groups.ResultsRemarkable alteration of essential fatty acids/long chain polyunsaturated fatty acids, omeg-3/omega-6 and significant lower levels of phospholipids were reported. Reciever Operating characteristics (ROC) analysis of the measured parameters revealed a satisfactory level of sensitivity and specificity.ConclusionEssential fatty acids/long chain polyunsaturated fatty acids and omeg-3/omega-6 ratios, phosphatidylethanolamine, phosphatidylserine and phosphatidylcholine could be used as potential biomarkers that point to specific mechanisms in the development of autism and may help tailor treatment or prevention strategies.

Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia.

OBJECTIVE This study aims to clarify the relationship between blood Pb(2+) concentration as a ubiquitous environmental pollutant and plasma neurotransmitters as biochemical parameters that reflect brain function in Saudi autistic patients. METHODS RBCs lead content together with plasma concentration of gamma aminobutyric acid (GABA), serotonin (5HT) and dopamine (DA) were measured in 25 Saudi autistic patients and compared to 16 age-matching control samples. RESULTS The obtained data recorded that Saudi autistic patients have a remarkable higher levels of Pb(2+) and significantly elevated levels of GABA, 5HT and DA compared to healthy subjects. ROC analysis revealed satisfactory values of specificity and sensitivity of the measured parameters. CONCLUSION This study suggests that postnatal lead toxicity in autistic patients of Saudi Arabia could represent a causative factor in the pathogenesis of autism. Elevated GABA, 5HT and DA were discussed in relation to the chronic lead toxicity recorded in the investigated autistic samples.