Increased Protein Oxidation Research Articles

Hepatic GPx1 and GIT1 expression altered by ethanol exposure during third trimester-equivalent development

Background Ethanol (EtOH) exposure throughout gestation and breastfeeding leads to multiple adverse outcomes in the hepatic system. Under oxidative stress, alterations in the liver are related to the inhibition of induced nitric oxide synthase activity in sinusoidal cells as a consequence of low expression of G-protein-coupled receptor (GPCR)-kinase interacting (GIT1). Here, we hypothesized that both glutathione peroxidase 1 (GPx1) and GIT1 could be altered by EtOH exposure during the third trimester of human equivalent development. Methods We exposed rats during the third trimester equivalent [postnatal days (PD) 2-8] to moderate levels of maternal EtOH (20%). GPx1 and GIT1 expression was detected by western blotting, and the antioxidant activity of glutathione peroxidase GPx and the concentration of hepatic carbonyl groups (CG were determined by spectrophotometry. Serum biochemistry parameters such as alanine aminotransferase (ALT), glucose (gluc), cholesterol (chol), and triglycerides (TG) were also measured. Results We found that ethanol decreased both GIT1 and GPx1 selenoprotein expression, affecting GPx antioxidant activity and increasing protein oxidation. Conclusions These results demonstrate for the first time that the GPx antioxidant system altered by EtOH exposure during the third trimester of development is related to a parallel decrease in GIT1 expression [1].

Dual modification of the aggregation behavior and in vitro digestion of oxidized pine kernel protein via a combination of homogenization and succinylation

Protein oxidation affects the high-value utilization of nuts as oxidative attack causes protein aggregation, thereby challenging their technological functionality. Herein, a strategy using homogenization-assisted octenyl succinic anhydride (OSA) modification was proposed to tailor the structure, aggregation behavior, and digestive characteristics of oxidized pine kernel proteins. Results indicated that the ratio of α-helices to β-turns ranged from as low as 0.43 up to 0.67 after homogenization, suggesting greater molecular flexibility. With increasing protein oxidation, the acylation degree exhibited an inverted V-shaped trend, peaking at 67.22 %. OSA treatment reduced the aggregation rate and prolonged the lag time of proteins by stabilizing the α-helices and β-turns, increasing hydrogen bonding, and decreasing hydrophobicity. This increased the solubility of oxidized pine kernel proteins by ~30 % and improved their fluidity and thermal stability. A lower degree of succinylation was associated with higher free sulfhydryl content and surface hydrophobicity, which facilitated the thermal aggregation and the formation of elastomeric gels. Furthermore, the in vitro dynamic digestion and morphological observations of hydrolysis products indicated that cotreated proteins exhibited higher digestibility and formed small spherical particles ranging from 405.50 to 676.50 nm. These findings provide a promising approach to mitigate the adverse effects of oxidation on nut proteins.

Effects of gestational hypothyroidism on mouse brain development: Gabaergic systems and oxidative stress

Hormonal imbalance during pregnancy is a risk factor for neuropsychiatric impairment in the offspring. It has been suggested that hypothyroidism leads to dysfunction of cortical GABAergic interneurons and inhibitory system development that in turn underlies impairment of the central nervous system. Here we investigated how gestational hypothyroidism affected offspring GABAergic system development as well as redox regulation parameters, because of previous links identified between the two. Experimental Gestational Hypothyroidism (EGH) was induced in CD-1 mice with 0.02% methimazole (MMI) in drinking water from embryonic day 9 (E9) until tissue collection at embryonic day 14 (E14) or E18. We examined GABAergic cell distribution and inhibitory system development gene expression as well as redox relevant gene expression and direct measures across all embryos regardless of sex. Intrauterine restriction of maternal thyroid hormones significantly impacted both of these outcomes in brain, as well as altering redox regulation in the placenta. GAD67+ neuronal migration was reduced, accompanied by a disruption in gene expression influencing GABAergic cell migration and cortical inhibitory neural system development. EGH also altered embryonic brain gene expression of Gpx1, Nfe2l2, Cat levels in the dorsal E14 brains. Additionally, EGH resulted in elevated TBARS, Gpx1 and Nfe2l2 in the ventral E18 brains. Furthermore, EGH downregulated placental Gpx1 gene expression at E14 and increased protein oxidation at E18. These findings support the hypothesis that sufficient maternal thyroid hormone supply to the fetus influences central nervous system development, including processes of GABAergic system development and redox equilibrium.

The Effects of Apricot Kernels and Pure Amygdalin on the Structural, Oxidative, and Inflammatory Characteristics of Rabbit Testicular Tissue

Background: Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments including cancer. Nevertheless, little is known regarding the toxic and therapeutic doses of AMG, particularly in terms of male reproduction. Hence, this study evaluates selected qualitative characteristics of rabbit testicular tissue following in vivo administration of AMG or apricot kernels for 28 days. Methods: The rabbits were randomly divided into five groups (Control, P1, P2, P3, P4). The Control received no AMG/apricot kernels while the experimental groups P1 and P2 received a daily intramuscular injection of amygdalin at a dose of 0.6 and 3.0 mg/kg of body weight (b.w.) for 28 days, respectively. P3 and P4 received a daily dose of 60 and 300 mg/kg b.w. of crushed apricot kernels mixed with feed for 28 days, respectively. Changes to the testicular structure were quantified morphometrically, while tissue lysates were subjected to the evaluation of reactive oxygen species (ROS) production, total antioxidant capacity, activities of antioxidant enzymes, and glutathione concentration. The extent of damage to the proteins and lipids was quantified as well. Levels of selected cytokines were determined by the enzyme-linked immunosorbent assay while a luminometric approach was used to assess the activity of caspases. Results: Rabbits treated with 3.0 mg/kg b.w. AMG presented a significantly increased protein oxidation (p = 0.0118) accompanied by a depletion of superoxide dismutase (p = 0.0464), catalase (p = 0.0317), and glutathione peroxidase (p = 0.0002). Significantly increased levels of interleukin-1 beta (p = 0.0012), tumor necrosis factors alpha (p = 0.0159), caspase-3/7 (p = 0.0014), and caspase-9 (p = 0.0243) were also recorded in the experimental group P2 when compared to the Control. No effects were observed in the rabbits treated with apricot kernels at the oxidative, inflammatory, and histopathological levels. Conclusions: Apricot kernels did not induce toxicity in the testicular tissues of male rabbits, unlike pure AMG, which had a negative effect on male reproductive structures carried out through oxidative, inflammatory, and pro-apoptotic mechanisms.

Glucose addition and oven-heating of pork stimulate glycoxidation and protein carbonylation, while reducing lipid oxidation during simulated gastrointestinal digestion

In the present study, it was investigated if glucose addition (3 or 5%) to pork stimulates glycoxidation (pentosidine, PEN), glycation (Maillard reaction products, MRP), lipid oxidation (4-hydroxy-2-nonenal, 4-HNE; hexanal, HEX; thiobarbituric acid reactive substances, TBARS), and protein oxidation (protein carbonyl compounds, PCC) during various heating conditions and subsequent in vitro gastrointestinal digestion. An increase in protein-bound PEN level was observed during meat digestion, which was significantly stimulated by glucose addition (up to 3.3-fold) and longer oven-heating time (up to 2.5-fold) of the meat. These changes were accompanied by the distinct formation of MRP during heating and digestion of the meats. Remarkably, stimulated glyc(oxid)ation was accompanied by increased protein oxidation, whereas lipid oxidation was decreased, indicating these reactions are interrelated during gastrointestinal digestion of meat. Glucose addition generally didn't affect these oxidative reactions when pork was packed preventing air exposure and oven-heated until a core temperature of 75 °C was reached.

Glycated LDL generates reactive species that damage cell components, oxidize hemoglobin and alter surface morphology in human erythrocytes

Low-density lipoprotein (LDL) transports cholesterol to various tissues via the blood. Glycation of LDL occurs during hyperglycemic condition which is characterised by persistently high blood glucose level. Circulating erythrocytes can come in direct contact with glycated LDL (G-LDL). The objective of this study was to investigate the effect of G-LDL on human erythrocytes, specifically on hemoglobin, intracellular generation of reactive species and the antioxidant defence system. Isolated erythrocytes were incubated with G-LDL (3 and 6 mg/ml) and native LDL (6 mg/ml) at 37 °C for 24 h. Native LDL and G-LDL untreated erythrocytes were similarly incubated at 37 °C and served as control. G-LDL treatment increased hemolysis compared to control and native LDL-treated erythrocytes. Incubation of erythrocytes with G-LDL led to an increase in protein oxidation and lipid peroxidation while greatly decreasing the total sulfhydryl content. It also significantly enhanced hemoglobin oxidation, heme degradation, and the release of free iron moiety. Treatment with G-LDL led to an appreciable increase in the production of reactive oxygen and nitrogen species. The antioxidant power and activities of major antioxidant enzymes were drastically reduced, while critical membrane-bound enzymes were inhibited. The surface morphology of G-LDL-treated erythrocytes was altered leading to the formation of echinocytes. Importantly, treatment of erythrocytes with native LDL did not significantly affect the above-mentioned parameters and values were similar to the corresponding controls. Thus, G-LDL is cytotoxic to human erythrocytes and causes oxidative damage to cell components. This can reduce the oxygen-transporting ability of blood and also result in red cell senescence and anemia.

Exposure to low-concentration fipronil impairs survival, behavior, midgut morphology and physiology of Aedes aegypti larvae

The Aedes aegypti mosquito is a vector for various arboviruses, including dengue and yellow fever. Insecticides, such as pyrethroids and organophosphates, are widely used to manage and control these insects. However, mosquitoes have developed resistance to these chemicals. Therefore, this study aimed to investigate the effects of the commercial formulation of fipronil (Tuit® Florestal; 80% purity) on the survival, behavior, morphology, and proteins related to signaling pathways of the midgut in A. aegypti larvae under controlled laboratory conditions. Significant reductions in immature survival were observed in all concentrations of fipronil tested. Low insecticide concentration (0.5 ppb) led to decreased locomotor activity in the larvae and caused disorganization of the epithelial tissue in the midgut. Moreover, exposure to the insecticide decreased the activity of detoxifying enzymes such as catalase, superoxide dismutase, and glutathione-S-transferase. On the other hand, the insecticide increased protein oxidation and nitric oxide levels. The detection of LC3, caspase-3, and JNK proteins, related to autophagy and apoptosis, increased after exposure. However, there was a decrease in the positive cells for ERK 1/2. Furthermore, the treatment with fipronil decreased the number of positive cells for the proteins FMRF, Prospero, PH3, Wg, Armadillo, Notch, and Delta, which are related to cell proliferation and differentiation. These findings demonstrate that even at low concentrations, fipronil exerts larvicidal effects on A. aegypti by affecting behavior and enzymatic detoxification, inducing protein oxidation, free radical generation, midgut damage and cell death, and inhibiting cell proliferation and differentiation. Thus, this insecticide may represent a viable alternative for controlling the spread of this vector.

Redox Biomarkers - An Effective Tool for Diagnosing COVID-19 Patients and Convalescents.

COVID-19 triggers the overproduction of reactive oxygen species (ROS) which, in combination with a weakened antioxidant barrier, can lead to protein oxidation and lipid peroxidation. The aim of this study was to evaluate enzymatic and non-enzymatic antioxidants, the overall redox potential, and protein and lipid peroxidation products in COVID-19 patients, convalescents, and healthy subjects, and to the determine the diagnostic applicability of these parameters in COVID-19 patients. The study involved 218 patients with COVID-19, 69 convalescents, and 48 healthy subjects who were selected for the research based on age and sex. The study was conducted between 20 February 2021 and 20 November 2021 in Białystok, Poland. The antioxidant barrier, redox status, and oxidative damage products were assessed in serum/plasma samples with the use of colorimetric and spectrophotometric assays. Glutathione reductase (GR) activity was higher, whereas total antioxidant capacity (TAC) was lower in COVID-19 patients than in convalescents (p<0.0001) and the control group (p<0.0001). The concentrations of advanced glycation end products (AGEs), advanced oxidation protein products (AOPP), 4-hydroxynonenal (4-HNE), and malondialdehyde (MDA) were higher in COVID-19 patients (p<0.0001) and convalescents (p<0.0001) than in the control group. AGEs were the most effective diagnostic biomarker for differentiating COVID-19 patients from the control group (AUC=0.9971) and convalescents from the control group (AUC=1.000). An infection with the SARS-CoV-2 disrupts the redox balance and increases protein oxidation and lipid peroxidation. AGEs fulfill the criteria for a potential diagnostic biomarker in COVID-19 patients and convalescents.

Number of denatured rigor cross-bridges determines the intracellular volume shrinkage in porcine muscle fibre under PSE-inducing condition

Earlier onset of rigor mortis is a critical physiological progress occurring in the development of pale soft and exudative (PSE) meat. However, how rigor cross-bridges denature under different physiological conditions and their impacts on water-holding capacity remains unclear. To address this scientific question, we firstly established a method to quantify the extent of rigor cross-bridge denaturation using skinned fibres prepared from porcine longissimus thoracis et lumborum muscle. Effects of pH and temperature on the kinetics of rigor cross-bridge denaturation, actomyosin denaturation and shrinkage of muscle fibre were studied. We then manipulated the number of rigor cross-bridges before the denaturation condition was initiated (pH 5.5, 38 °C). Results suggested that the loss of water-holding capacity in PSE meat is determined by the number of denatured rigor cross-bridges. Physiochemical analysis on myofibrils demonstrated that increase in protein oxidation, surface hydrophobicity and loss of electrostatic repulsive force between myofibrils may be involved in the mechanism.

Morphological Effects and In Vitro Biological Mechanisms of Radiation-Induced Cell Killing by Gold Nanomaterials.

Gold nanomaterials have been shown to augment radiation therapy both in vitro and in vivo. However, studies on these materials are mostly phenomenological due to nanoparticle heterogeneity and the complexity of biological systems. Even accurate quantification of the particle dose still results in bulk average biases; the effect on individual cells is not measured but rather the effect on the overall population. To perform quantitative nanobiology, we coated glass coverslips uniformly at varying densities with Au nanoparticle preparations with different morphologies (45 nm cages, 25 nm spheres, and 30 nm rods). Consequently, the effect of a specific number of particles per unit area in contact with breast cancer cells growing on the coated surfaces was ascertained. Gold nanocages showed the highest degree of radiosensitization on a per particle basis, followed by gold nanospheres and gold nanorods, respectively. All three materials showed little cytotoxic effect at 0 Gy, but clonogenic survival decreased proportionally with the radiation dose and particle coverage density. A similar trend was seen in vivo in the combined treatment antitumor response in 4T1 tumor-bearing animals. The presence of gold affected the type and quantity of reactive oxygen species generated, specifically superoxide and hydroxyl radicals, and the concentration of nanocages correlated with the development of more numerous double-stranded DNA breaks and increased protein oxidation as measured by carbonylation. This work demonstrates the dependence on morphology and concentration of radiation enhancement by gold nanomaterials and may lead to a novel method to differentiate intra- and extracellular functionalities of gold nanomedicine treatment strategies. It further provides insights that can guide the rational development of gold nanomaterial-based radiosensitizers for clinical use.

Assessment of Serum Levels of Advanced Oxidation Protein Products in Type 2 Diabetic Patients with and without Retinopathy Taking Different Antidiabetic Treatments

The goal of this study was to investigate the protein peroxidation role by measuring serum levels of advanced oxidation protein products (AOPP) in type 2 diabetic patients with or without retinopathy and comparing them to controls to see if circulating AOPP levels can be used as a detection biomarker for DR. And see which of the two widely used antidiabetic treatment groups had the most impact on this oxidative stress marker. The groups were divided into two subgroups: 1) 70 type 2 diabetic patients (36 male, 34 female), 35 with diabetic retinopathy (DR) and 35 with no evidence of DR, and 2) non-diabetic controls (11 male, 9 female) were chosen from Ibn AL-Haitham Hospital for Ophthalmology and a Specialized Center for Endocrinology and Diabetes. AOPP levels were significantly higher in diabetic patients with (12.5±5.6 ng/ml) or without DR (5.1±4 ng/ml) when compared to those of controls (1.45 0.8 ng/ml) (p&lt;0.05). AOPP levels were higher in the late stage of DR compared to the early stage(14 3.15 ng/ml ) and ( 10 2.13 ng/ml) respectively so. Furthermore, Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) cause a better reduction in AOPP levels compared to Sulfonylureas (SUs) in the NDR group. Increased protein oxidation may involve in the pathogenesis and severity of DR and the serum AOPP levels have the prospect to become a marker for the diagnosis of DR. DPP-4 inhibitors were better in slowing the progression of the disease compared to SUs.

Impact of chronic heat stress on behavior, oxidative status and meat quality traits of fast-growing broiler chickens.

This research aimed to investigate, through a multifactorial approach, the relationship among some in-vivo parameters (i.e., behavior and blood traits) in broilers exposed to chronic HS, and their implications on proximate composition, technological properties, and oxidative stability of breast meat. A total of 300 Ross 308 male chickens were exposed, from 35 to 41days of age, to either thermoneutral conditions (TNT group: 20°C; six replicates of 25 birds/each) or elevated ambient temperature (HS group: 24h/d at 30°C; six replicates of 25 birds/each). In order to deal with thermal stress, HS chickens firstly varied the frequency of some behaviors that are normally expressed also in physiological conditions (i.e., increasing "drinking" and decreasing "feeding") and then exhibited a behavioral pattern finalized at dissipating heat, primarily represented by "roosting," "panting" and "elevating wings." Such modifications become evident when the temperature reached 25°C, while the behavioral frequencies tended to stabilize at 27°C with no further substantial changes over the 6days of thermal challenge. The multifactorial approach highlighted that these behavioral changes were associated with oxidative and inflammatory status as indicated by lower blood γ-tocopherol and higher carbonyls level (0.38 vs. 0.18nmol/mL, and 2.39 vs. 7.19nmol/mg proteins, respectively for TNT and HS; p < 0.001). HS affected breast meat quality by reducing the moisture:protein ratio (3.17 vs. 3.01, respectively for TNT and HS; p < 0.05) as well as the muscular acidification (ultimate pH = 5.81 vs. 6.00, respectively; p < 0.01), resulting in meat with higher holding capacity and tenderness. HS conditions reduced thiobarbituric acid reactive substances (TBARS) concentration in the breast meat while increased protein oxidation. Overall results evidenced a dynamic response of broiler chickens to HS exposure that induced behavioral and physiological modifications strictly linked to alterations of blood parameters and meat quality characteristics.

Neuroanatomical zones of human traumatic brain injury reveal significant differences in protein profile and protein oxidation: Implications for secondary injury events.

Traumatic brain injury (TBI) causes significant neurological deficits and long-term degenerative changes. Primary injury in TBI entails distinct neuroanatomical zones, i.e., contusion (Ct) and pericontusion (PC). Their dynamic expansion could contribute to unpredictable neurological deterioration in patients. Molecular characterization of these zones compared with away from contusion (AC) zone is invaluable for TBI management. Using proteomics-based approach, we were able to distinguish Ct, PC and AC zones in human TBI brains. Ct was associated with structural changes (blood-brain barrier (BBB) disruption, neuroinflammation, axonal injury, demyelination and ferroptosis), while PC was associated with initial events of secondary injury (glutamate excitotoxicity, glial activation, accumulation of cytoskeleton proteins, oxidative stress, endocytosis) and AC displayed mitochondrial dysfunction that could contribute to secondary injury events and trigger long-term degenerative changes. Phosphoproteome analysis in these zones revealed that certain differentially phosphorylated proteins synergistically contribute to the injury events along with the differentially expressed proteins. Non-synaptic mitochondria (ns-mito) was associated with relatively more differentially expressed proteins (DEPs) compared to synaptosomes (Syn), while the latter displayed increased protein oxidation including tryptophan (Trp) oxidation. Proteomic analysis of immunocaptured complex I (CI) from Syn revealed increased Trp oxidation in Ct > PC > AC (vs. control). Oxidized W272 in the ND1 subunit of CI, revealed local conformational changes in ND1 and the neighboring subunits, as indicated by molecular dynamics simulation (MDS). Taken together, neuroanatomical zones in TBI show distinct protein profile and protein oxidation representing different primary and secondary injury events with potential implications for TBI pathology and neurological status of the patients.

Deregulated intracellular pathways define novel molecular targets for HBV-specific CD8 T cell reconstitution in chronic hepatitis B

In chronic HBV infection, elevated reactive oxygen species levels derived from dysfunctional mitochondria can cause increased protein oxidation and DNA damage in exhausted virus-specific CD8 T cells. The aim of this study was to understand how these defects are mechanistically interconnected to further elucidate T cell exhaustion pathogenesis and, doing so, to devise novel T cell-based therapies. DNA damage and repair mechanisms, including parylation, CD38 expression, and telomere length were studied in HBV-specific CD8 T cells from chronic HBV patients. Correction of intracellular signalling alterations and improvement of antiviral T cell functions by the NAD precursor nicotinamide mononucleotide and by CD38 inhibition was assessed. Elevated DNA damage was associated with defective DNA repair processes, including NAD-dependent parylation, in HBV-specific CD8 cells of chronic HBV patients. NAD depletion was indicated by the overexpression of CD38, the major NAD consumer, and by the significant improvement of DNA repair mechanisms, and mitochondrial and proteostasis functions by NAD supplementation, which could also improve the HBV-specific antiviral CD8 T cell function. Our study delineates a model of CD8 T cell exhaustion whereby multiple interconnected intracellular defects, including telomere shortening, are causally related to NAD depletion suggesting similarities between T cell exhaustion and cell senescence. Correction of these deregulated intracellular functions by NAD supplementation can also restore antiviral CD8 T cell activity and thus represents a promising potential therapeutic strategy for chronic HBV infection. Correction of HBV-specific CD8 T cell dysfunction is believed to represent a rational strategy to cure chronic HBV infection, which however requires a deep understanding of HBV immune pathogenesis to identify the most important targets for functional T cell reconstitution strategies. This study identifies a central role played by NAD depletion in the intracellular vicious circle that maintains CD8 T cell exhaustion, showing that its replenishment can correct impaired intracellular mechanisms and reconstitute efficient antiviral CD8 T cell function, with implications for the design of novel immune anti-HBV therapies. As these intracellular defects are likely shared with other chronic virus infections where CD8 exhaustion can affect virus clearance, these results can likely also be of pathogenetic relevance for other infection models.

Potential Role of Oxidative Stress in the Production of Volatile Organic Compounds in Obesity.

Obesity is associated with numerous health issues such as sleep disorders, asthma, hepatic dysfunction, cancer, renal dysfunction, diabetes, cardiovascular complications, and infertility. Previous research has shown that the distribution of excess body fat, rather than excess body weight, determines obesity-related risk factors. It is widely accepted that abdominal fat is a serious risk factor for illnesses associated with obesity and the accumulation of visceral fat promotes the release of pro-oxidants, pro-inflammatory, and reactive oxygen species (ROS). The metabolic process in the human body produces several volatile organic compounds (VOCs) via urine, saliva, breath, blood, skin secretions, milk, and feces. Several studies have shown that VOCs are released by the interaction of ROS with underlying cellular components leading to increased protein oxidation, lipid peroxidation, or DNA damage. These VOCs released via oxidative stress in obese individuals may serves as a biomarker for obesity-related metabolic alterations and disease. In this review, we focus on the relationship between oxidative stress and VOCs in obesity.

Assessment of Serum Level of Protein Carbonyl as a Marker of Protein Oxidation in Patients with Type 2 Diabetes Mellitus

Background: Diabetes mellitus is a chronic disease with an increasing prevalence worldwide and characterized by an increase in oxidative stress and inflammation. The most important factor that is responsible for oxidative stress and production of reactive oxygen species (ROS) is hyperglycemia. The major targets of ROS are proteins. The most common and widely used biomarker of severe oxidative protein damage is protein carbonyl content. The study was designed to assess the serum level of protein carbonyl as a marker of protein oxidation in patients with type 2 diabetes mellitus and to evaluate the effect of age, body weight, waist circumference, diabetic control and disease duration on the level of protein carbonyl. Subjects and Methods: This is a case-control study that included 91 patients with type 2 diabetes mellitus Eighty-five non-diabetic apparently healthy subjects matched for both age and sex with cases were enrolled as controls. Fasting blood samples were collected after an overnight fasting to measure protein carbonyl, fasting blood sugar, lipid profile, and glycated hemoglobin. Results: The level of serum protein carbonyl was significantly higher in diabetic patients than in controls and positively correlated with glycated hemoglobin, age of participant and disease duration as well as with body mass index and waist circumference. Conclusion: Diabetes mellitus is associated with an increase in protein oxidation in term of increase in the level of serum protein carbonyl with significant association in those who had poor glycemic control, obesity, higher age, and prolonged disease duration suggest that the carbonyl content of protein may be useful in evaluating the disease progression. Significant positive correlation of protein carbonyl together with waist circumference suggest that individual with central obesity are more susceptible to protein oxidation.

Hyperglycemia enhances the generation of ROS and RNS that impair antioxidant power and cause oxidative damage in human erythrocytes.

Hyperglycemia is a state in which excess glucose circulates in blood. Erythrocytes are in direct contact with this high glucose concentration and are greatly affected by it. We have examined the effect of hyperglycemic condition on isolated human erythrocytes under in vitro conditions. Erythrocytes were incubated with different concentrations of glucose (5, 15, 30, 45 mmol/L) for 24 h, and several biochemical parameters were determined. Treatment with high glucose concentrations increased heme degradation and methemoglobin level, while methemoglobin reductase activity was decreased. A significant increase in protein oxidation and lipid hydroperoxides with a decrease in total sulfhydryl content was seen. This suggested the generation of oxidative stress, which was confirmed by an enhanced production of reactive oxygen and nitrogen species. Hyperglycemia led to a significant decline in the antioxidant power of erythrocytes, lowering their ability to quench free radicals and reduce metal ions to lower oxidation states. The plasma membrane redox system was upregulated, while ascorbate free radical reductase activity was lowered. Glucose exposure inhibited the enzymes of glycolysis and hexose monophosphate shunt. Electron microscopy showed morphological changes resulting in the formation of echinocytes. Thus, the hyperglycemic condition generates reactive species that oxidize proteins, hemoglobin, and lipids; impair the total antioxidant capacity; and alter morphology in human erythrocytes.

Role of Food Hydrocolloids as Antioxidants along with Modern Processing Techniques on the Surimi Protein Gel Textural Properties, Developments, Limitation and Future Perspectives.

Texture is an important parameter in determining the quality characteristics and consumer acceptability of seafood and fish protein-based products. The addition of food-based additives as antioxidants (monosaccharides, oilgosaccharides, polysaccharides and protein hydrolysates) in surimi and other seafood products has become a promising trend at an industrial scale. Improvement in gelling, textural and structural attributes of surimi gel could be attained by inhibiting the oxidative changes, protein denaturation and aggregation with these additives along with new emerging processing techniques. Moreover, the intermolecular crosslinking of surimi gel can be improved with the addition of different food hydrocolloid-based antioxidants in combination with modern processing techniques. The high-pressure processing (HPP) technique with polysaccharides can develop surimi gel with better physicochemical, antioxidative, textural attributes and increase the gel matrix than conventional processing methods. The increase in protein oxidation, denaturation, decline in water holding capacity, gel strength and viscoelastic properties of surimi gel can be substantially improved by microwave (MW) processing. The MW, ultrasonication and ultraviolet (UV) treatments can significantly increase the textural properties (hardness, gumminess and cohesiveness) and improve the antioxidative properties of surimi gel produced by different additives. This study will review potential opportunities and primary areas of future exploration for high-quality surimi gel products. Moreover, it also focuses on the influence of different antioxidants as additives and some new production strategies, such as HPP, ultrasonication, UV and MW and ohmic processing. The effects of additives in combination with different modern processing technologies on surimi gel texture are also compared.

NRF2 activation protects against valproic acid-induced disruption of neurogenesis in P19 cells

Valproic acid (VPA) is a commonly prescribed antiepileptic drug that causes fetal valproate syndrome (FVS) in developing embryos exposed to it. Symptoms of FVS include neural tube defects (NTDs), musculoskeletal abnormalities, and neurodevelopmental difficulties. One proposed mechanism of VPA-induced developmental toxicity is via oxidative stress, defined as the disruption of redox-sensitive cell signaling. We propose that redox imbalances caused by VPA exposure result in improper cellular differentiation that may contribute to FVS. In undifferentiated P19 mouse embryonal carcinoma cells treated with VPA, glutathione disulfide (GSSG) concentrations were higher and the glutathione (GSH)/GSSG redox potential (Eh) was more oxidizing compared to vehicle-treated control cells, both of which are indications of potential intracellular oxidative stress. Interestingly, VPA had no effect on GSH or GSSG levels in differentiated P19 neurons. Undifferentiated cells pretreated with 3H-1,2-dithiole-3-thione (D3T), an inducer of the nuclear factor erythroid 2-related factor 2 (NRF2) antioxidant response that combats cellular redox disruption, were protected from VPA-induced alterations to the GSH/GSSG system. To assess differential periods of susceptibility, P19 cells were exposed to VPA at various time points during their neuronal differentiation. Cells exposed to VPA early in the differentiation process did not undergo normal neurogenesis as measured by POU domain, class 5, transcription factor 1 (OCT4) and tubulin beta-3 chain (βIII-tubulin), markers of cell stemness and neuronal differentiation, respectively. Neurogenesis was improved with D3T pretreatments prior to VPA exposure. Furthermore, differentiating P19 cells treated with VPA exhibited increased protein oxidation that was diminished with D3T pretreatment. These findings demonstrate that VPA inhibits neurogenesis and propose NRF2-mediated redox homeostasis as a means to promote normal neuronal differentiation, thereby potentially decreasing the prevalence of FVS outcomes.

Investigation of the Effects of MK-801 on Oxidative Stress, Inflammation and Ghrelin Levels in Brain Tissue in Convulsions Caused by Scopolamine Administration and Feeding in Starving Mice

In this study, the effect of MK-801, one of the noncompetitive N-methyl-D-aspartate (NMDA) receptor antagonists, on convulsions that occurred in mice that were given scopolamine and then fed experimentally after 48 hours of fasting was investigated. In our study, 36 Balb/C adult male mice weighing 25-30 g were used. Mice were randomly selected and divided into 6 groups. These are control, scopolamine (3 mg/kg/i.p.), low dose MK-801 (0.17 mg/kg/i.p.), high dose MK-801 (0.51 mg/kg/i.p.), scopolamine + low dose MK- 801 and scopolamine+ high dose MK-801 groups. After the injections, the animals in all groups were taken to the monitoring cages and fed 20 minutes after the injections. Convulsion onset times and severity of animals in all groups were measured. At the end of the follow-up period, animals in all groups, including the control group, were sacrificed under anesthesia with ketamine (50 g/kg/i.p.) and xylazine (10 mg/kg/i.p.), their blood was drawn and brain tissues were isolated. Blood ghrelin levels of all animals and some oxidative stress and inflammation markers and ghrelin levels in brain tissue were measured. Analysis of the study was done using SPSS v16.0 statistical program. The statistical significance level was taken as p&lt;0.05 in the calculations. It was observed that scopolamine administration caused a decrease in catalase and superoxide dismutase activities and ghrelin levels, and increased protein oxidation and inflammatory response. MK-801 treatment has been found to both delay the incidence of convulsions and suppress oxidative stress and inflammation (p&lt;0.05). We think that these effects of MK-801 are due to the increased ghrelin level, as the application of MK-801 also causes an increase in the level of ghrelin. Keywords: Convulsion, Scopolamine, MK-801, Oxidative Stress, Ghrelin DOI: 10.7176/JSTR/7-10-01