Autism is a severe developmental disorder with poorly understood etiology. Oxidative stress in autism has been studied at the membrane level and also by measuring products of lipid peroxidation, detoxifying agents (such as glutathione), and antioxidants involved in the defense system against reactive oxygen species (ROS). Lipid peroxidation markers are elevated in autism, indicating that oxidative stress is increased in this disease. Levels of major antioxidant serum proteins, namely transferrin (iron-binding protein) and ceruloplasmin (copper-binding protein), are decreased in children with autism. There is a positive correlation between reduced levels of these proteins and loss of previously acquired language skills in children with autism. The alterations in ceruloplasmin and transferrin levels may lead to abnormal iron and copper metabolism in autism. The membrane phospholipids, the prime target of ROS, are also altered in autism. The levels of phosphatidylethanolamine (PE) are decreased, and phosphatidylserine (PS) levels are increased in the erythrocyte membrane of children with autism as compared to their unaffected siblings. Several studies have suggested alterations in the activities of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase, and catalase in autism. Additionally, altered glutathione levels and homocysteine/methionine metabolism, increased inflammation, excitotoxicity, as well as mitochondrial and immune dysfunction have been suggested in autism. Furthermore, environmental and genetic factors may increase vulnerability to oxidative stress in autism. Taken together, these studies suggest increased oxidative stress in autism that may contribute to the development of this disease. A mechanism linking oxidative stress with membrane lipid abnormalities, inflammation, aberrant immune response, impaired energy metabolism and excitotoxicity, leading to clinical symptoms and pathogenesis of autism is proposed.
There is significant evidence that the pathogenesis of several neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease, Friedreich's ataxia and amyotrophic lateral sclerosis, may involve the generation of reactive oxygen species and mitochondrial dysfunction. Here, we review the evidence for a disturbance of glutathione homeostasis that may either lead to or result from oxidative stress in neurodegenerative disorders. Glutathione is an important intracellular antioxidant that protects against a variety of different antioxidant species. An important role for glutathione was proposed for the pathogenesis of Parkinson's disease, because a decrease in total glutathione concentrations in the substantia nigra has been observed in preclinical stages, at a time at which other biochemical changes are not yet detectable. Because glutathione does not cross the blood-brain barrier other treatment options to increase brain concentrations of glutathione including glutathione analogs, mimetics or precursors are discussed.
It has been suggested that oxidative stress and/or mercury compounds play an important role in the pathophysiology of autism. This study compared for the first time the cerebellar levels of the oxidative stress marker 3-nitrotyrosine (3-NT), mercury (Hg) and the antioxidant selenium (Se) levels between control and autistic subjects. Tissue homogenates were prepared in the presence of protease inhibitors from the frozen cerebellar tissue of control (n=10; mean age, 15.5 years; mean PMI, 15.5 hours) and autistic (n=9; mean age 12.1 years; mean PMI, 19.3 hours) subjects. The concentration of cerebellar 3-NT, determined by ELISA, in controls ranged from 13.69 to 49.04 pmol g-1 of tissue; the concentration of 3-NT in autistic cases ranged from 3.91 to 333.03 pmol g-1 of tissue. Mean cerebellar 3-NT was elevated in autism by 68.9% and the increase was statistically significant (p=0.045). Cerebellar Hg, measured by atomic absorption spectrometry ranged from 0.9 to 35 pmol g-1 tissue in controls (n=10) and from 3.2 to 80.7 pmol g-1 tissue in autistic cases (n=9); the 68.2% increase in cerebellar Hg was not statistically significant. However, there was a positive correlation between cerebellar 3-NT and Hg levels (r=0.7961, p=0.0001). A small decrease in cerebellar Se levels in autism, measured by atomic absorption spectroscopy, was not statistically significant but was accompanied by a 42.9% reduction in the molar ratio of Se to Hg in the autistic cerebellum. While preliminary, the results of the present study add elevated oxidative stress markers in brain to the growing body of data reflecting greater oxidative stress in autism.
Autism spectrum disorders are complex neuro-developmental disorders whose neurobiology is proposed to be associated with oxidative stress which is induced by reactive oxygen species. The process of oxidative stress can be a target for therapeutic interventions. In this study, we aimed to review the role of oxidative stress, plasma glutathione (GSH), and related factors as the potential sources of damage to the brain as well as the possible related factors which reduce the oxidative stress. Methylation capacity, sulfates level, and the total glutathione level are decreased in autism. On the other hand, both oxidized glutathione and the ratio of oxidized to reduced glutathione are increased in autism. In addition, the activity of glutathione peroxidase, superoxide dismutase, and catalase, as a part of the antioxidative stress system are decreased. The current literature suggests an imbalance of oxidative and anti-oxidative stress systems in autism. Glutathione is involved in neuro-protection against oxidative stress and neuro-inflammation in autism by improving the anti-oxidative stress system. Decreasing the oxidative stress might be a potential treatment for autism.
Our work reveals that the aerial parts of Pulmonaria officinalis L. are a new source of yunnaneic acid B. We studied antioxidant activity and cytotoxicity of this compound (1–50 μg/mL) and its contents in various plant extracts. This is the first study confirming the presence of yunnaneic acid B in P. officinalis L. and Pulmonaria obscura Dumort and hence in the Boraginaceae family. Determination of 1,1-diphenyl-2-picrylhydrazyl radical reduction and peroxynitrite-scavenging efficacy in inorganic experimental systems provided EC50 values of 7.14 and 50.45 μg/mL, respectively. Then we examined the antioxidant action of yunnaneic acid B in blood plasma under peroxynitrite-induced oxidative stress in vitro. Yunnaneic acid B effectively diminished oxidative damage to blood plasma proteins and lipids. Furthermore, it was able to prevent the peroxynitrite-induced decrease in nonenzymatic antioxidant capacity of blood plasma. Additionally, cytotoxicity of yunnaneic acid B (at concentrations ≤50 μg/mL) toward peripheral blood mononuclear cells was excluded.
Oxidative stress is known to impair architecture and function of cells, which may lead to various chronic diseases, and therefore therapeutic and nutritional interventions to reduce oxidative damages represent a viable strategy in the amelioration of oxidative stress-related disorders, including neurodegenerative diseases. Over the past decade, a variety of natural polysaccharides from functional and medicinal foods have attracted great interest due to their antioxidant functions such as scavenging free radicals and reducing oxidative damages. Interestingly, these antioxidant polysaccharides are also found to attenuate neuronal damages and alleviate cognitive and motor decline in a range of neurodegenerative models. It has recently been established that the neuroprotective mechanisms of polysaccharides are related to oxidative stress-related pathways, including mitochondrial function, antioxidant defense system and pathogenic protein aggregation. Here, we first summarize the current status of antioxidant function of food-derived polysaccharides and then attempt to appraise their anti-neurodegeneration activities.
Heat shock protein (Hsp) 70 has been reported to protect various cells and tissues from ischemic damage. However, the molecular mechanisms of the protection are incompletely understood. Ischemia induces significant alterations in cellular redox status that plays a critical role in cell survival/death pathways. We investigated the effects of Hsp70 overexpression on cellular redox status in Madin-Darby canine kidney (MDCK) cells under both hypoxic and ischemic conditions with 3 different approaches: reactive oxygen species (ROS) measurement by a fluorescence probe, redox environment evaluation by a hydroxylamine spin probe, and redox status assessment by the glutathione/glutathione disulfide (GSH/GSSG) ratio. Results from each of these approaches showed that the redox status in Hsp70 cells was more reducing than that in control cells under either hypoxic or oxygen and glucose deprivation (OGD) conditions. In order to determine the mechanisms that mediated the alterations in redox state in Hsp70 cells, we measured the activities of glutathione peroxidase (GPx) and glutathione reductase (GR), two GSH-related antioxidant enzymes. We found that OGD exposure increased GPx and GR activities 47% and 55% from their basal levels (no stress) in Hsp70 cells, compared to only 18% and 0% increase in control cells, respectively. These data, for the first time, indicate that Hsp70 modulates the activities of GPx and GR that regulate cellular redox status in response to ischemic stress, which may be important in Hsp70's cytoprotective effects.
Remarkable interest has risen in the idea that oxidative/nitrosative stress is mediated in the etiology of numerous human diseases. Oxidative/Nitrosative stress is the result of an disequilibrium in oxidant/antioxidant which reveals from continuous increase of Reactive Oxygen and Reactive Nitrogen Species production. The aim of this review is to emphasize with current information the importance of antioxidants which play the role in cellular responce against oxidative/nitrosative stress, which would be helpful in enhancing the knowledge of any biochemist, pathophysiologist, or medical personnel regarding this important issue. Products of lipid peroxidation have commonly been used as biomarkers of oxidative/nitrosative stress damage. Lipid peroxidation generates a variety of relatively stable decomposition end products, mainly α, β-unsaturated reactive aldehydes, such as malondialdehyde, 4-hydroxy-2-nonenal, 2-propenal (acrolein) and isoprostanes, which can be measured in plasma and urine as an indirect index of oxidative/nitrosative stress. Antioxidants are exogenous or endogenous molecules that mitigate any form of oxidative/nitrosative stress or its consequences. They may act from directly scavenging free radicals to increasing antioxidative defences. Antioxidant deficiencies can develop as a result of decreased antioxidant intake, synthesis of endogenous enzymes or increased antioxidant utilization. Antioxidant supplementation has become an increasingly popular practice to maintain optimal body function. However, antoxidants exhibit pro-oxidant activity depending on the specific set of conditions. Of particular importance are their dosage and redox conditions in the cell.
The aim of this work was to evaluate the antioxidant potential of teas prepared from twenty-four commercially available berries and flowers of Sambucus nigra L. in relation to their phenolic profile, as reflected by the most representative phenolic acids (caffeic, chlorogenic, p-coumaric, ferulic, gallic and syringic acids); flavonols (quercetin, kaempferol, myricetin and rutin); and total phenolic (TPC), phenolic acid (TAC) and flavonoid (TFC) contents. The infusions prepared from elderflowers contained more abundant phenolic compounds than the elderberry infusions. The TPC of these infusions ranged from 19.81 to 23.90 mg of gallic acid equivalents/g dry weight of sample (GAE/g DW) for elderberries and from 15.23 to 35.57 mg GAE/g DW for elderflowers, whereas the TFC ranged from 2.60 to 4.49 mg of rutin equivalents/g dry weight of sample (RUTE/g DW) in elderberry infusions and from 5.27 to 13.19 mg RUTE/g DW in elderflower infusions. Among the phenolic compounds quantified in this study, quercetin (2.07–9.48 mg/g DW) and myricetin (1.17–9.62 mg/g DW) had the highest concentrations in the teas prepared from berries and flowers, respectively. Moreover, the antioxidant potential of elder infusions assessed by 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical and ferric reducing antioxidant power (FRAP) assays revealed that the teas prepared from flowers had higher mean DPPH and FRAP activities than the teas prepared from berries. Therefore, elder beverages could be important dietary sources of natural antioxidants that contribute to the prevention of diseases caused by oxidative stress.