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Considerable disturbances in post-translational protein phosphorylation have recently been discovered in multiple neurological disorders. Casein kinase-2 (CK2) is a tetrameric Ser/Thr protein kinase that phosphorylates a large number of substrates and contributes in several cellular physiological and pathological processes. CK2 is highly expressed in the mammalian brain and catalyzes the phosphorylation of a large number of substrates that are crucial in neuronal or glial homeostasis and inflammatory signaling processes across synapses. In this study, we investigated the impact of auditory integration therapy (AIT) for the treatment of sensory processing abnormalities in autism on plasma CK2 levels. A total of 25 ASD children, aged between 5 and 12 years, were enrolled and participated in the present research study. AIT was performed for two weeks, for a period of 30 min, twice a day, with a 3 h interval between sessions. Before and after AIT, the Childhood Autism Rating Scale (CARS), Social Responsiveness Scale (SRS), and Short Sensory Profile (SSP) scores were calculated, and plasma CK2 levels were assayed using an ELISA test. The CARS and SRS indices of autism severity improved as a result of AIT, which could be related to the decreased level of plasma CK2. However, the mean value of the SSP scores was not significantly increased after AIT. The relationship between CK2 downregulation and glutamate excitotoxicity, neuro-inflammation, and leaky gut, as etiological mechanisms in ASD, was proposed and discussed. Further research, conducted on a larger scale and with a longer study duration, are required to assess whether the cognitive improvement in ASD children after AIT is related to the downregulation of CK2.
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Agaricus bisporus, the most widely cultivated mushroom, is safe to eat and enriched with protein and secondary metabolites. We prepared silver nanoparticles (AgNPs) from two varieties of A. bisporus and tested their antibacterial activity The synthesized AgNPs were initially confirmed by UV-Vis spectroscopy peaks at 420 and 430 nm for white and brown mushrooms AgNPs, respectively. AgNPs were further characterized by zeta sizer, transmission electronic microscopy (TEM), Fourier transform infrared (FTIR), and energy-dispersive X-ray spectroscopy (EDX) prior to antibacterial activity by the well diffusion method against six bacterial strains which include Staphylococcus aureus, Staphylococcus epidermis, Bacillus subtilis, Escherichia coli, Salmonella typhi, and Pseudomonas aeruginosa. TEM results revealed a spherical shape with an average diameter of about 11 nm in the white mushroom extract and 5 nm in the brown mushroom extract. The presence of elemental silver in the prepared AgNPs was confirmed by EDS. The IR spectrum of the extract confirmed the presence of phenols, flavonoids, carboxylic, or amide groups which aided in the reduction and capping of synthesized AgNPs. The AgNPs from both extracts showed almost the same results; however, nanoparticles prepared from brown mushrooms were smaller in size with strong antibacterial activity.
Assuntos
Nanopartículas Metálicas , Prata , Prata/farmacologia , Prata/química , Nanopartículas Metálicas/química , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Bacillus subtilis , Espectroscopia de Infravermelho com Transformada de Fourier , Testes de Sensibilidade MicrobianaRESUMO
BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social interaction and restricted and repetitive behaviors. Neuroinflammation and abnormal lipid mediators have been identified in multiple investigations as an acknowledged etiological mechanism of ASD that can be targeted for therapeutic intervention. METHODS: In this study, multiple regression and combined receiver operating characteristic (ROC) curve analyses were used to determine the relationship between the neuroinflammatory marker α-synuclein and lipid mediator markers related to inflammation induction, such as cyclooxygenase-2 and prostaglandin-EP2 receptors, in the etiology of ASD. Additionally, the study aimed to determine the linear combination that maximizes the partial area under ROC curves for a set of markers. Forty children with ASD and 40 age- and sex-matched controls were enrolled in the study. Using ELISA, the levels of α-synuclein, cyclo-oxygenase-2, and prostaglandin-EP2 receptors were measured in the plasma of both groups. Statistical analyses using ROC curves and multiple and logistic regression models were performed. RESULTS: A remarkable increase in the area under the curve was observed using combined ROC curve analyses. Moreover, higher specificity and sensitivity of the combined markers were reported. CONCLUSIONS: The present study indicates that measurement of the predictive value of selected biomarkers related to neuroinflammation and lipid metabolism in children with ASD using a ROC curve analysis should lead to a better understanding of the etiological mechanism of ASD and its link with metabolism. This information may facilitate early diagnosis and intervention.
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Transtorno do Espectro Autista/sangue , Ciclo-Oxigenase 2/sangue , Receptores de Prostaglandina E Subtipo EP2/sangue , alfa-Sinucleína/sangue , Transtorno do Espectro Autista/diagnóstico , Biomarcadores/sangue , Estudos de Casos e Controles , Pré-Escolar , Humanos , Masculino , Doenças Neuroinflamatórias/sangue , Curva ROCRESUMO
Males are more likely to develop autism as a neurodevelopmental disorder than females, but the mechanisms underlying male susceptibility are not fully understood. In this paper, we used a well-characterized propionic acid (PPA) rodent model of autism to study sex differences in stress hormones, antioxidants' status, and the neuroimmune response that may contribute to the preponderance of autism in males. Sprague Dawley rats of both sexes were divided into a saline-treated group as controls and PPA-treated groups, receiving 250 mg/kg of PPA per day for three days. Animals' social behavior was examined using the three-chamber social test. Hormones (ACTH, corticosterone, melatonin, and oxytocin), oxidative stress biomarkers (glutathione, glutathione-S-transferase, and ascorbic acid), and cytokines (IL-6, IL-1α, IL-10, and IFNγ) were measured in the brain tissue of all the animals. The results showed a sex dimorphic social response to PPA treatment, where males were more susceptible to the PPA treatment and exhibited a significant reduction in social behavior with no effects observed in females. Also, sex differences were observed in the levels of hormones, antioxidants, and cytokines. Female rats showed significantly higher corticosterone and lower oxytocin, antioxidants, and cytokine levels than males. The PPA treatment later modulated these baseline differences. Our study indicates that the behavioral manifestation of autism in PPA-treated males and not females could be linked to neural biochemical differences between the sexes at baseline, which might play a protective role in females. Our results can contribute to early intervention strategies and treatments used to control autism, an increasingly prevalent disorder.
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Antioxidantes/metabolismo , Transtorno Autístico/imunologia , Transtorno Autístico/metabolismo , Hormônios/sangue , Sistema Nervoso/imunologia , Interação Social , Animais , Transtorno Autístico/induzido quimicamente , Química Encefálica , Corticosterona/metabolismo , Citocinas/metabolismo , Feminino , Masculino , Ocitocina/metabolismo , Propionatos , Ratos , Ratos Sprague-Dawley , Caracteres SexuaisRESUMO
Studies have reported a reciprocal interaction between metabolic disorders and the human gut microbial composition. However, more information is still needed concerning the gut microbiome related to metabolic disorders such as Diabetes. The aim of the present study was to reveal whether stool samples collected from normal individuals and from diabetic subjects with or without retinopathy differ in their gut microbial composition. Data showed higher Bacteroides ratio in diabetic groups gut composition with no significant difference of bacterial strains in diabetic subjects with or without retinopathy compared to lean (control) individuals gut microbiota. These findings indicated that the gut microbiota is altered in accordance to the presence of metabolic disorders. However, further studies have to be elaborated in terms of gut microbial composition with diabetes.
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Bacteroidetes/isolamento & purificação , Diabetes Mellitus/microbiologia , Retinopatia Diabética/microbiologia , Fezes/microbiologia , Adulto , Bacteroidetes/classificação , Estudos de Casos e Controles , Estudos Transversais , Feminino , Trato Gastrointestinal/microbiologia , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Neuroinflammation plays a major role in the pathogenesis of autism because the cytokine levels are typically disturbed in the brain in autistic patients. Prebiotics-rich diet maintains the healthy gut microbiota and hence can regulate the neuroinflammation indirectly. The study aimed to investigate the role of bee pollen and propolis in ameliorating neuroinflammation, including cytokine levels, in an animal model of autism. METHODS: Hamsters were classified as four groups: Group I, control; Group II, autistic model/animals treated with 250 mg propionic acid (PPA)/kg body weight (BW)/day for 3 days; Group III, animals treated with bee pollen at a dose of 250 mg/kg BW/day for 4 weeks; and Group IV, animals treated with propolis at a dose of 250 mg/kg BW/day for 4 weeks. Neuroinflammatory responses were evaluated using the levels of interferon γ (IFN-γ), interleukin 1 alpha (IL-1α), IL-6, IL-10, IL-12 (p70), vascular endothelial growth factor (VEGF), and tumor necrosis factor α (TNFα). RESULTS: Significant decrease of IL-10 (P<0.026), VEGF (P<0.005), and TNFα(P<0.005) levels and increased IL-1α (P<0.032), IL-6(P<0.028), and IFN-γ (P<0.013) levels were observed between the four studied groups. The neurotoxic effects of PPA was clearly presented as much higher IL-6, as pro-inflammatory cytokine (P<0.05), concomitant with much lower IL-10, as anti-inflammatory cytokine(P<0.015) compared to controls. Both bee pollen and propolis were effective in ameliorating the neurotoxic effects of PPA demonstrating non-significant changes of IL-6 and IL-10 when compared to control healthy hamsters. CONCLUSIONS: Our findings indicate that both bee pollen and propolis protect against neuroinflammation in the rodent model of autism. However, further studies are needed to investigate the clinical benefits of prebiotics-rich diet in neurodevelopmental disorders, such as autism.
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Transtorno Autístico/tratamento farmacológico , Disbiose/tratamento farmacológico , Inflamação/tratamento farmacológico , Pólen/metabolismo , Propionatos/farmacologia , Própole/farmacologia , Animais , Transtorno Autístico/induzido quimicamente , Transtorno Autístico/metabolismo , Química Encefálica/efeitos dos fármacos , Citocinas/análise , Modelos Animais de Doenças , Disbiose/induzido quimicamente , Inflamação/induzido quimicamente , Masculino , MesocricetusRESUMO
Many enzymes are involved in numerous pathologies which are related to metabolic reactions and inflammatory diseases such as pancreatic lipase, α-amylase, α-glucosidase and xanthine oxidase and secreted phospholipases A2 (Group IIA, V and X), respectively. Therefore, inhibiting these enzymes offer the potential to block production of more inflammatory substances and decrease the risk factors for cardiovascular diseases. The purpose of this study was to investigate some potent, bioavailable and selective inhibitors of some catalytic proteins implicated to metabolic syndrome and their antioxidant effects from various solvent extracts of R. frangula leaves. The anti-inflammatory, obesity, diabete and XO potentials were evaluated through analyses of inhibition activities of corresponding metabolites.The water extract exhibited an important inhibitory effect on human, dromedary and stingray sPLA2-G IIA achieved an IC50 of 0.16±0.06, 0.19±0.05 and 0.07±0.01 mg/mL, respectively. Likewise, the same fraction demonstrated the highest pancreatic lipase inhibitory activity using two different substrates. Indeed, 50% of dromedary pancreatic lipase inhibition was demonstrated for 5 min and 15 min using olive oil and TC4 substrates, respectively. Besides, it was established that methanolic extract had more effective inhibitory lipase activity than ORLISTAT used as a specific inhibitor of gastric, pancreatic and carboxyl ester lipase for treating obesity, with an IC50 of 5.51±0.27 and 91.46±2.3 µg/mL, respectively. In the case of α-amylase, α-glucosidase and xanthine oxidase, the crude methanolic extract showed a potential inhibitory effect with an IC50 of 45±3.45, 3±0.15 and 27±1.71 µg/mL, respectively. Conclusively, R. frangula leaves extracts showed a potential value of some sPLA2, some metabolic enzymes and XO inhibitors as anti-inflammatory and metabolic syndrome drugs.
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Inibidores Enzimáticos/farmacologia , Enzimas/metabolismo , Inflamação/enzimologia , Extratos Vegetais/farmacologia , Folhas de Planta/química , Rhamnus/química , Animais , Humanos , Concentração Inibidora 50 , Metanol/química , Solventes , Ácido Taurodesoxicólico/farmacologiaRESUMO
The gut and the liver are closely linked to each other, as changes in the gut microbiota can play a significant role in the development of many liver diseases. Gut bacteria respond rapidly to changes in diet and thus can affect the liver through their metabolites. The impact of a high lipid diet on the liver in the presence of an altered gut flora modulated by ampicillin was investigated. The study was performed on 30 male Western albino rats randomly divided into 3 groups: control (phosphate buffered saline treated), group II (ampicillin 50 mg/kg for three weeks to induce microbiota alterations and fed on standard diet) and group III (same dose of ampicillin and fed on a lipid rich diet). Stool samples were collected for qualitative determination of bacteria. Serum hepato-specific markers, in addition to Glutathione (GSH), Lipid peroxidase (MDA), Glutathione-S- transferase(GST), and vitamin C in liver tissues, were measured. Altered gut microbiota significantly increased the level of the hepato-specific marker MDA and reduced the GST, GSH and vitamin C levels. However, animals fed a lipid rich diet displayed a more significant shift in hepatic markers and antioxidants. Moreover, a new switch in composition of the gut bacteria was observed by feeding the lipid rich diet. Our study showed that bacterial overgrowth in the gut can be associated with liver dysfunction and that a high lipid diet can promote the overgrowth of some liver damaging microflora during antibiotic treatment.
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Dieta Hiperlipídica , Microbioma Gastrointestinal , Fígado/metabolismo , Ampicilina/farmacologia , Animais , Antibacterianos/farmacologia , Ácido Ascórbico/metabolismo , Glutationa/metabolismo , Glutationa Transferase/metabolismo , Fígado/enzimologia , Masculino , Peroxidases/metabolismo , RatosRESUMO
Genetic polymorphism in proinflammatory cytokine genes may be associated with the etiology of preterm birth (PTB). The current study was designed with the aim to explore the association of genetic polymorphisms and mRNA expression of IL-1α, IL-1ß, and TNF-α gene with preterm birth in the Saudi population. Genotyping of genomic DNA of 50 PTB patients and an equal number of controls were carried out using TaqMan Genotyping assay kits. Gene expression of each gene was carried out using quantitative RT-PCR. The cytokine levels in the serum of PTB patients and controls were measured by ELISA. A statistically significant association was observed between the rs361525 alleles (G and A) of TNF-α and PTB, where the mutant A allele was significantly protective against PTB development (OR= 0.362; χ2=4.31; p=0.038). The gene expression of all studied genes (IL1α, IL-1ß, IL-6, and TNF-α) was higher in the PTB patients, but the results reached significance only for IL-1ß (p=0.035). Elevated gene expression was also evident from the level of these proteins in plasma, where the level of IL1α, IL-ß were significantly higher in the serum of PTB patients compared to the controls, however, IL6 and TNF-α were significantly lower despite higher gene expression. For IL6, the lower level could be due to tocolytic treatment that was given to all women suffering from PTB. Receiver operating curves (ROC) were drawn for the studied cytokines. In conclusion, this study revealed that rs361525 polymorphism plays a role as a protective marker for PTB and the levels of IL-1α, IL-6, TNF- α can be used as predicative biomarkers for PTB I Saudi women.
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Interleucina-1alfa/genética , Interleucina-1beta/genética , Interleucina-6/genética , Polimorfismo de Nucleotídeo Único , Nascimento Prematuro/genética , Fator de Necrose Tumoral alfa/genética , Adulto , Feminino , Frequência do Gene , Humanos , Recém-Nascido , Interleucina-1alfa/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Gravidez , Nascimento Prematuro/sangue , Nascimento Prematuro/epidemiologia , Arábia Saudita/epidemiologia , Transcriptoma , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: Abnormal phospholipid metabolism is a major component of many neurodevelopmental disorders including autism. Oral administration of propionic acid (PPA) can produce behavioral abnormalities and biochemical features in rodents similar to those observed in autism and can thus be used as a model to understand impaired brain fatty acid metabolism in autism. METHODS: The present study was designed to understand alterations in phospholipid metabolism in the brain of a rodent model of autism and to explore omega-3 and vitamin B12 as remedies. Five groups of rats were selected: Group 1 was the control. Group 2 was the rodent model of autism treated with a neurotoxic dose of PPA. Group 3 was given vitamin B12 cobalamin (16.7 mg/kg/day) for 30 days after PPA treatment. Group 4 was given pharmaceutical grade Omega-3 (200 mg cholesterol free-DHA/kg body weight/day), a product of Madre lab, Germany, for 30 days after PPA treatment for 3 days. Group 5 was given a combined dose of ω-3 + Vitamin B12 for the same duration post-PPA treatment. Phospholipid levels and Phospholipase A2 were measured in the brain homogenates of all the groups. ELISA and western blotting were used to detect the cPLA2 protein level. RESULTS: A significant decrease in phospholipid levels and a significant increase in cPLA2 were found in brain tissue of PPA-treated rats; however, both ω-3 and vitamin B12 were efficient in ameliorating the neurotoxic effect of PPA. CONCLUSION: Both ω-3 and vitamin B12 may play a role in ameliorating impaired phospholipid metabolism in autism; however, proper clinical trials are needed.
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Transtorno Autístico/tratamento farmacológico , Colesterol/metabolismo , Ácidos Graxos Ômega-3/metabolismo , Vitamina B 12/metabolismo , Animais , Transtorno Autístico/metabolismo , Transtorno Autístico/patologia , Suplementos Nutricionais , Modelos Animais de Doenças , Humanos , Hidrólise/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Fosfolipases A2/metabolismo , Fosfolipídeos/metabolismo , Propionatos/administração & dosagem , RatosRESUMO
The present study investigated the therapeutic effects of probiotics on brain intoxication induced by clindamycin and propionic acid (PPA) in hamsters. Fifty golden Syrian hamsters were randomly divided into five experimental groups of ten animals each: (A) control group receiving phosphate buffered saline; (B) oral buffered PPA-treated group being administered with a neurotoxic dose of 250 mg/kg PPA during three days; (C) oral clindamycin-treated group receiving a single dose of 30 mg clindamycin/kg; and (D, E) the two therapeutic groups being administered the same doses of clindamycin and PPA followed by probiotics for three weeks at a daily dose of 0.2 g/kg. Biochemical parameters of energy metabolism and oxidative stress were examined in brain homogenates from all hamsters. The development of pathogenic bacteria was monitored on stool samples from all hamsters. Descriptive changes in fecal microbiota and overgrowth of Clostridium species in clindamycin and PPA treated hamsters were recorded. Interestingly, probiotics were shown effective to restore normal gut microbiota. Clindamycin and PPA treatments caused an elevation in lipid peroxidation and catalase activity, as oxidative stress markers, together with a reduction in GST activity and GSH level. Energy metabolism impairment was ascertained via the activation of creatine kinase and a decrease of lactate dehydrogenase. These findings suggest that bacteria overgrowth caused by PPA and clindamycin was efficient to illustrate signs of neuronal toxicity. The present study indicates that probiotic treatment can improve poor detoxification, oxidative stress, and altered gut microbiota as mechanisms implicated in the etiology of many neurological disorders.
Assuntos
Antibacterianos/toxicidade , Encéfalo/efeitos dos fármacos , Clindamicina/toxicidade , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/administração & dosagem , Propionatos/toxicidade , Administração Oral , Animais , Animais Recém-Nascidos , Encéfalo/metabolismo , Cricetinae , Metabolismo Energético/efeitos dos fármacos , Metabolismo Energético/fisiologia , Microbioma Gastrointestinal/fisiologia , Mesocricetus , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Distribuição AleatóriaRESUMO
The original version of this article unfortunately contained a mistake. The family name of the fourth author listed in the title was incorrect, and the correct name is Nadine Moubayed, as noted in the addresses. Her name is now corrected in the author group of this article.
RESUMO
Increasing evidence suggests that the gut microbiota plays a key role in the central nervous system (CNS), and alterations of the gut microbiota composition due to environmental factors can contribute to neurodevelopmental disorders. Animal modeling may help to identify drugs that can normalize the altered gut microbiota and thereby ameliorate abnormal brain signaling pathways. The purpose of the present study was to investigate the therapeutic potency of probiotics such as Bifidobacteria and Lactobacilli on glutamate excitotoxicity as a neurotoxic effect induced by clindamycin and propionic acid (PPA) in juvenile hamsters. Fifty young golden Syrian hamsters weighing between 60 and 70 g were enrolled in the study. The hamsters were randomly divided into five groups, each with ten hamsters. The hamsters in the control group only received phosphate-buffered saline orally. The PPA-treated group received a neurotoxic dose of 250 mg PPA/kg body weight (BW)/day for three days. The clindamycin-treated group received 30 mg clindamycin/kg BW as a single orogastric dose on the day the experiment started. The two therapeutic groups received the same doses of PPA and clindamycin followed by 0.2 g probiotic/kg BW for three weeks. Biochemical parameters related to glutamate excitotoxicity were investigated in brain homogenates from each group of hamsters. Additionally, the development of pathogenic bacteria was monitored in stool samples from all groups. The microbiology results of the present study revealed descriptive changes in the fecal microbiota and the appearance of Clostridium species in the hamsters treated with clindamycin and PPA. Additionally, the effectiveness of the probiotic in the restoration of the normal gut microbiota was demonstrated. Moreover, clindamycin and PPA were found to induce a significant depletion of Mg2+ and γ-aminobutyric acid (GABA) and a remarkable increase in the Na+/Mg2+ and glutamate/GABA ratios but non-significant changes in the absolute levels of K+, Na+ and glutamate. The bacteria overgrowth induced by PPA and clindamycin in the present study effectively showed signs of neuronal toxicity. The study indicates that probiotics can be used safely to ameliorate glutamate excitotoxicity mostly through increasing depleted GABA and Mg2+ and decreasing the excitatory neurotransmitter, glutamate.
Assuntos
Encéfalo/efeitos dos fármacos , Clindamicina/farmacologia , Ácido Glutâmico/metabolismo , Probióticos/farmacologia , Propionatos/farmacologia , Ácido gama-Aminobutírico/metabolismo , Animais , Transtorno Autístico , Encéfalo/metabolismo , Cricetinae , Modelos Animais de Doenças , Microbioma Gastrointestinal/efeitos dos fármacosRESUMO
Autism spectrum disorder (ASD) affects about 1% of the world's population. Vitamin D is thought to be essential for normal brain development and modulation of the immune system. Worldwide about 1 billion people are affected by vitamin D deficiency. High-sensitivity C-reactive protein (hs-CRP), cytochrome P450 2E1 (CYP2E1) and 8-hydroxy-2'-deoxyguanosine (8-OH-dG) are biomarkers related to inflammation and oxidative stress. In the present study, these biomarkers were together with serum 25-hydroxyvitamin D (25(OH)D3) analyzed in 28 (mean age seven years) Saudi male patients with ASD. The study was conducted to determine if there is any relationship between vitamin D levels, the tested biomarkers and the presence and severity of ASD. The hope was to identify if these biomarkers may be useful for early ASD diagnosis. The Childhood Autism Rating Scale (CARS) and the Social Responsiveness Scale (SRS) were used to measure autism severity. The results of the ASD children were compared with 27 age and gender-matched neurotypical controls. The data indicated that Saudi patients with ASD have significantly lower plasma levels of 25(OH)D3 than neurotypical controls (38 ng/ml compared to 56 ng/ml, respectively; [P = 0.001]). Surprisingly, the levels of CYP2E1 were lower in the children with ASD than the neurotypical controls (0.48 ± 0.08 vs. 69 ± 0.07 ng/ml, respectively; P = 0.001). The ASD children also had significantly higher levels of hs-CRP (0.79 ± 0.09 vs. 0.59 ± 0.09 ng/ml, respectively; P = 0.001) and 8-OH-dG (8.17 ± 1.04 vs. 4.13 ± 1.01 ng/ml, respectively; P = 0.001, compared to neurotypical age and gender-matched controls. The values for hs-CRP and 8-OH-dG did not correlate [P < 0.001] with autism severity. There was found a relationship between autism severity on the CARS scale and the levels of 25(OH)D3 and CYP1B1. But this was not found for SRS. All four biomarkers seemed to have good sensitivity and specificity, but the sample size of the present study was too small to determine clinical usefulness. The findings also indicate that inadequate levels of vitamin D play a role in the etiology and severity of autism. Furthermore, the results of the present study suggest the possibility of using 25(OH)D3, CYP1B1, hs-CRP and 8-OH-dG, preferably in combination, as biomarkers for the early diagnosis of ASD. However, further research is needed to evaluate this hypothesis.
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Transtorno do Espectro Autista/diagnóstico , Biomarcadores/análise , Diagnóstico Precoce , Vitamina D/metabolismo , Adolescente , Transtorno do Espectro Autista/tratamento farmacológico , Comportamento/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Vitamina D/farmacologiaRESUMO
BACKGROUND: Valproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism. METHODS: The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12.5th day of gestation. At 7 days from their birth, the animals were supplemented with a specific dose of curcumin. Forty neonatal male Western Albino rats were divided into four groups. Rats in group I received only phosphate-buffered saline, rats in group II were the prenatal VPA exposure newborns, rats in group III underwent prenatal VPA exposure supplemented with postnatal curcumin, and rats in group IV were given only postnatal curcumin supplements. RESULTS: VPA rats exhibited delayed maturation and lower body and brain weights with numerous signs of brain toxicity, such as depletion of IFN-γ, serotonin, glutamine, reduced glutathione, glutathione S-transferase, lipid peroxidase with an increase in CYP450, IL-6, glutamate, and oxidized glutathione. A curcumin supplement moderately corrected these dysfunctions and was especially noticeable in improving delayed maturation and abnormal weight. CONCLUSIONS: Curcumin plays a significant therapeutic role in attenuating brain damage that has been induced by prenatal VPA exposure in rats; however, its therapeutic role as a dietary supplement still must be certified for use in humans.
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Anticonvulsivantes/efeitos adversos , Transtorno Autístico/tratamento farmacológico , Curcumina/administração & dosagem , Complicações na Gravidez/tratamento farmacológico , Ácido Valproico/efeitos adversos , Animais , Anticonvulsivantes/uso terapêutico , Transtorno Autístico/induzido quimicamente , Encéfalo/efeitos dos fármacos , Encéfalo/crescimento & desenvolvimento , Encéfalo/metabolismo , Suplementos Nutricionais/análise , Modelos Animais de Doenças , Feminino , Glutationa/metabolismo , Humanos , Masculino , Atividade Motora , Gravidez , Ratos , Ratos Wistar , Serotonina/metabolismo , Ácido Valproico/uso terapêuticoRESUMO
BACKGROUND: It is now well documented that postnatal exposure to certain chemicals has been reported to increase the risk of autism spectrum disorder. Propionic acid (PA), as a metabolic product of gut microbiotaandas a commonly used food additive, has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental neurotoxic agents and drugs that can ameliorate neurotoxicity and may thereby aid in the treatment of autism. The present study investigated the ameliorative effects of natural bee pollen against acute and sub-acute brain intoxication induced by (PA) in rats. METHODS: Twenty-four young male Western Albino ratswere enrolled in the present study. They were classified into four equal groups, eachwith6 rats. The control group received only phosphate buffered saline; the oral buffered PA-treated groups (II and III) received a neurotoxic dose of 750 mg/kg body weight divided in 3 dose of 250 mg/kg body weight/day serving asthe acute group and 750 mg/kg body weight divided in 10 equal dose of 75 mg/kg body weight/day as the sub-acute group. The fourth group received 50 mg bee pollen for 30 days after PA-acute intoxication. RESULTS: The obtained data showed that the PA-treated groups demonstrated multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), dopamine and nor-adrenaline, together withan increase in IFN-γ and caspase 3. Bee pollen was effective in ameliorating the neurotoxic effect of PA. All measured parameters demonstrated minimal alteration in comparison with thecontrol animal than did those of acute and sub-acute PA-treated animals. CONCLUSIONS: In conclusion, bee pollen demonstrates anti-inflammatory and anti-apoptotic effects while ameliorating the impaired neurochemistry of PA-intoxicated rats.
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Transtorno Autístico/tratamento farmacológico , Abelhas , Pólen , Animais , Transtorno Autístico/induzido quimicamente , Encéfalo/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Propionatos/toxicidade , RatosRESUMO
BACKGROUND: Reducing exposure to toxic environmental agents is a critical area of intervention. Prenatal or postnatal exposure to certain chemicals has been documented to increase the risk of autism spectrum disorder. Propionic acid (PA) found in some foods and formed as a metabolic product of gut microbiota has been reported to mediate the effects of autism. Results from animal studies may help to identify environmental contaminants and drugs that produce or prevent neurotoxicity, and may thereby aid in the treatment of neurodevelopmental disorders such as autism. The present study investigated the protective and/or therapeutic effects of vitamin D against brain intoxication induced by propionic acid (PPA) in rats. METHODS: Twenty-eight young male Western Albino rats were enrolled in the present study. They were grouped into four equal groups of 7. The control group received only phosphate buffered saline; the oral buffered PPA-treated group received a neurotoxic dose of 250 mg/kg body weight/day for 3 days; and the Vitamin D-protected group received 1000 IU/kg/day of alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks, after which the rats were injected with PPA 250 mg/Kg body weight/day for 3 days. The fourth group received PPA 250 mg/Kg body weight/day for 3 days followed by alpha, 25-dihydroxyvitamin D (3) (1, 25-VD) for two weeks (Vitamin D therapeutic effect). Vitamin D and calcium were measured in the plasma of the four studied groups. Serotonin, interferon gamma (IFN-γ), glutathione-s-transferase activity and DNA double helix breaks were assayed in the brain tissue of the rats for all groups. RESULTS: The obtained data showed that the PPA-treated group demonstrated higher plasma vitamin D levels compared to the control rats, together with multiple signs of brain toxicity, as indicated by a depletion of serotonin (5HT), an increase in IFN-γ and inhibition of glutathione-s-transferase activity as three biomarkers of brain dysfunction. Additionally, Comet DNA assays showed remarkably higher tail length, tail DNA % damage and tail moment as a neurotoxic effect of PPA. CONCLUSIONS: Vitamin D showed a greater protective than therapeutic effect on PPA-induced neurotoxicity in rats, as there was a remarkable amelioration of the impaired biochemically measured parameters representing neurochemical, inflammation, and detoxification processes.