Intake of Oxidized Proteins and Amino Acids and Causative Oxidative Stress and Disease: Recent Scientific Evidences and Hypotheses

The exposure to reactive oxygen species (ROS) is an inevitable consequence of living in an aerobic world. The species contribute to the occurrence of oxidative stress in humans in which an uncontrolled production of ROS exceeds the endogenous antioxidant defences leading to the oxidative damage to essential cellular components, such as lipids, proteins, and DNA. The influence of diet on the modulation of the systemic redox status is recognized and, while some dietary components are found to be protective (that is, fruits and vegetables), others are recognized as pro‐oxidants (that is, processed meat and other animal‐source protein foods). Oxidized proteins and amino acids are potential promoters of luminal and postprandial oxidative stress; preliminary studies have actually reported noxious effects of these species in cultured cells and in experimental animals. However, the underlying pathological mechanisms remain poorly understood. The application of advanced methodological approaches based on mass spectrometric technologies and OMICS disciplines has enabled the elucidation of the molecular basis of the pathological effects of dietary oxidized proteins and amino acids. The present review collects the most recent evidences of the health risks of dietary protein oxidation and proposes reasonable hypotheses and future perspectives on the field.     

Effect of microbial biocontrol agents on alleviating oxidative damage of peach fruit subjected to fungal pathogen

Levels of protein carbonylation in peach fruits inoculated with four antagonistic yeasts (Pichia membranaefaciens, Cryptococcus laurentii, Candida guilliermondii and Rhodotorula glutinis) were significantly reduced in response to reactive oxygen species (ROS) caused by Monilinia fructicola. In control fruit without yeast treatments, proteins carbonylation obviously increased after inoculation with M. fructicola, ranging from molecular mass 20 to 120 kDa. However, in yeast-treated fruits, no proteins carbonylation was detected at 1 d, only a small quantity of carbonylation ranging from 28.5 to 45 kDa was found at 2 d. Antagonistic yeasts significantly stimulated the activities of chitinase, beta-1,3-glucanase, catalase (CAT), peroxidase (POD) and the expressions of relevant genes during all storage periods. These results suggest that yeast treatments may be related to alleviating proteins carbonylation and mitigating pathogen-induced oxidative damage, which result in decrease of fruit decay and imply that antioxidant defense response may be involved in the mechanisms of microbial biocontrol agents against fungal pathogen.     

Chemo-protective activity and characterization of phenolic extracts from Corema album

There is currently substantial interest in the cyto-protective effects of natural compounds against oxidative stress and in studying of the defense mechanisms involved. Corema album fruit is an edible berry consumed along the Atlantic littoral of the Iberian Peninsula. The aim of this study was to characterize the phenolic composition and evaluate the chemo-protective effects against oxidative stress of three phenolic extracts from this fruit on liver cells.Characterization of phenolic compounds, achieved by liquid chromatography and diode-array, mass spectrometry and electrospray ionization-time of flight-mass spectrometry detection, showed a main fraction of hydroxycinnamic acids. Liver HepG2 cells were treated with 1–40 μg/mL of the extracts and exposed to oxidative stress chemically induced. Cell viability, reactive oxygen species (ROS), reduced glutathione (GSH), antioxidant enzymes and biomarkers of oxidative damage were evaluated.Treatment of HepG2 cells with the extracts partially prevented ROS increase, GSH depletion, antioxidant enzymes over-activity and oxidative damage to proteins and lipids induced by stress. The results support the traditional use of C. album as a medicinal plant and suggest that inclusion of its berries in the diet would contribute to the protection afforded by fruits, vegetables and plant-derived beverages against oxidative stress related diseases.     

Heme, heme oxygenase and ferritin in vascular endothelial cell injury

Iron-derived reactive oxygen species are implicated in the pathogenesis of numerous vascular disorders including atherosclerosis, microangiopathic hemolytic anemia, vasculitis, and reperfusion injury. One abundant source of redox active iron is heme, which is inherently dangerous when released from intracellular heme proteins. The present review concerns the involvement of heme in vascular endothelial cell damage and the strategies used by endothelium to minimize such damage. Exposure of endothelium to heme greatly potentiates cell killing mediated by polymorphonuclear leukocytes and other sources of reactive oxygen. Free heme also promotes the conversion of low-density lipoprotein (LDL) into cytotoxic oxidized products. Only because of its abundance, hemoglobin probably represents the most important potential source of heme within the vascular endothelium; hemoglobin in plasma, when oxidized, transfers heme to endothelium and LDL, thereby enhancing cellular susceptibility to oxidant-mediated injury. As a defense against such toxicity, upon exposure to heme or hemoglobin, endothelial cells up-regulate heme oxygenase-1 and ferritin. Heme oxygenase-1 is a heme-degrading enzyme that opens the porphyrin ring, producing biliverdin, carbon monoxide, and the most dangerous product - free redox active iron. The latter can be effectively controlled by ferritin via sequestration and ferroxidase activity. Ferritin serves as a protective gene by virtue of antioxidant, antiapoptotic, and antiproliferative actions. These homeostatic adjustments have been shown effective in the protection of endothelium against the damaging effects of exogenous heme and oxidants. The central importance of this protective system was recently highlighted by a child diagnosed with heme oxygenase-1 deficiency, who exhibited extensive endothelial damage.     

Inhibitory property of Piper betel extract against photosensitization-induced damages to lipids and proteins

The protective activity of Piper betel ethanolic extract (PE) against the photosensitization-induced damage to lipids and proteins of rat liver mitochondria has been studied. PE could effectively prevent lipid peroxidation, as assessed by measuring thiobarbituric acid reactive substances, lipid hydroperoxide and conjugated diene. In addition, it prevented photo-induced oxidation of proteins in a concentration-dependent manner. Furthermore, its preventive capacity against iron-mediated lipid peroxidation was also confirmed. The protective activity of PE could be attributed to its free radical and singlet oxygen scavenging properties. The activity of PE was primarily due to its phenolic constituents, which were identified as chavibetol and 4-allylpyrocatechol.     

Use of the synthetic superoxide dismutase/catalase mimetic EUK-134 to compensate for seasonal antioxidant deficiency by reducing pre-existing lipid peroxides at the human skin surface

The generation of reactive oxygen species (ROS) in UV-exposed skin is believed to contribute to the photoaging process. The stratum corneum (SC) contains a variety of enzymatic and non-enzymatic antioxidants to protect against various environmental sources of free radicals. We have previously shown a seasonal variation in SC catalase activity with strong deactivation in sun-exposed skin in the summer, whereas SC superoxide dismutase (SOD) activity remained intact in those conditions. This potentially leads to the local overproduction of H(2)O(2). The oxidized lipid squalene hydroperoxide accumulates at the surface of sun-exposed skin in the summer and upon exposure to ultravoilet A (UVA) doses as low as 0.1 J cm(-2) and adequate protection against excessive lipid peroxidation at times of UV exposure should be aimed for. We have been using the induction of lipid hydroperoxides at the skin surface by a single dose of UVA (1 J cm(-2)) as a model system to evaluate the protective effect of antioxidants in vivo. Topical treatment with the synthetic SOD/catalase mimetic molecule (EUK-134) 1 h before UVA exposure reduced the level of lipid peroxides at the surface of UVA-exposed skin but also baseline peroxide levels on non-irradiated skin were reduced in a dose-dependent fashion. In contrast to alpha-tocopherol, EUK-134 even reduced the level of lipid peroxides at the surface of UVA-exposed skin when it was applied after irradiation. We confirmed that this salen-manganese complex was able to reduce squalene hydroperoxide levels in vitro, suggesting peroxidase-like activity towards organic peroxides. These data support the concept that the synthetic SOD/catalase mimetic EUK-134 might be able to compensate for seasonal deficiencies in antioxidant defense capacity at the skin surface, thereby contributing to an optimal protection of the skin against the accumulation of oxidative damage.     

Protein Oxidation: Basic Principles and Implications for Meat Quality

The involvement of oxidized proteins to the development of biological diseases has been studied for a few decades, but the effects and the mechanisms of protein oxidation in food systems are largely unknown. Protein oxidation is defined as the covalent modification of a protein induced either by the direct reactions with reactive oxygen species (ROS) or indirect reactions with secondary by-products of oxidative stress. ROS can cause oxidation in both amino acid side chains and protein backbones, resulting in protein fragmentation or protein–protein cross-linkages. Although all amino acids can be modified by ROS, cysteine, and methionine that are the most susceptible to oxidative changes due to high reaction susceptibility of the sulfur group in those amino acids. Oxidative modifications of proteins can change their physical and chemical properties, including conformation, structure, solubility, susceptibility to proteolysis, and enzyme activities. These modifications can be involved in the regulation of fresh meat quality and influence the processing properties of meat products. Oxidative stress occurs when the formation of oxidants exceeds the ability of antioxidant systems to remove the ROS in organisms. Increased levels of protein oxidation have been associated with various biological consequences, including diseases and aging, in humans and other animal species. The basic principles and products of protein oxidation and the implications of protein oxidation in food systems, especially in meat, are discussed in this review.     

Effects of flavonoids on the expression of the pro-inflammatory response in human monocytes induced by ligation of the receptor for AGEs

Increasing evidence has shown advanced glycation end products (AGEs) receptor ligation (RAGE) to be an important part of complex interactions of the oxidative stress and pro-inflammatory responses. In this study, flavonoids were used to monitor the protective effects against the oxidative damage and inflammation mediated by AGEs in human monocytes. S100B (RAGE ligand) treatment in human THP-1 monocytic cells (THP-1) significantly increased gene expression of the pro-inflammatory cytokines TNF-alpha and IL-1beta; chemokines MCP-1 and IP-10; adhesion factors platelet endothelial cell adhesion molecule (PECAM-1) and beta2-integrin; and pro-inflammatory cyclooxygenase-2 (COX-2). S100B treatment with quercetin and catechin in THP-1 cells had inhibitory effects on the expression of pro-inflammatory genes and protein levels. Quercetin and catechin could regulate S100B-activated oxidant stress-sensitive pathways through blocking p47phox protein expression. Treatment with quercetin and catechin could eliminate reactive oxygen species (ROS) to reduce oxidative stress stimulated by S100B in THP-1 cells. Quercetin and catechin also showed different regulatory abilities on mitogen-activated protein kinase (MAPK) signaling pathways by inhibiting protein expression in S100B-stimulated inflammatory responses in THP-1 cells. This study suggests that quercetin and catechin may be of benefit for diabetic vascular complications due to its antioxidant abilities against AGE-mediated oxidative stress through oxidative stress-sensitive and oxidative stress-responsive signaling pathways, which lead to inflammation in human monocytes.     

真菌毒素DON和ZEN的体外联合毒性评价

选取BEL7402细胞对脱氧雪腐镰刀菌烯醇（Deoxynivalenol,DON）和玉米赤霉烯酮（Zearalenone,ZEN）的联合毒性进行评价。首先将不同浓度的DON、ZEN以及其混合物染毒对数期的BEL7402细胞,刺激24 h后,对细胞增殖率、ROS活性氧水平、钙离子水平、细胞凋亡率以及凋亡相关靶点基因的表达等指标进行监测分析,并对两种毒素的联合毒性作用进行评价。结果表明,真菌毒素DON、ZEN均可抑制细胞活性,IC₅₀分别为9.3、27.2μg/m L,可导致细胞氧化应激损伤,提高细胞内活性氧水平以及钙离子浓度,显著上调凋亡关键基因p53、Bax,下调Bal-2基因,诱导细胞产生早期凋亡甚至坏死,多种毒性指标验证了这两种毒素对细胞的联合毒性作用表现为加和作用。      

Protective effect of carvacrol from <Emphasis Type="Italic">Thymus quinquecostatus</Emphasis> Celak against <Emphasis Type="Italic">tert</Emphasis>-butyl hydroperoxide-induced oxidative damage in Chang cells

Carvacrol is a monoterpenic phenol present in Thymus quinquecostatus Celak. The protective effects of carvacrol against tert-butyl hydroperoxide (t-BHP)-induced oxidative damage were investigated in human Chang cells. Cells treated with carvacrol extracts promoted Chang cell survival and protection was associated with stabilization of the mitochondrial membrane potential (MMP), prevention of oxidative stress-triggered reactive oxygen species (ROS), and lipid peroxidation (MDA production). In addition, Annexin V/PI, observed using Hoechst staining, indicated that carvacrol inhibited t-BHP-induced cell damage and stimulated the antioxidant capability of Chang cells due to elevation of glutathione (GSH) levels, which were reduced by t-BHP treatment. Carvacrol prevented oxidative stress-induced Chang cell damage via suppression of ROS and MDA levels, and increased GSH levels.     

The etiology of oxidative stress in the various species of animals,a review

Oxidative stress is the consequence of an imbalance of pro‐oxidants and antioxidants leading to cell damage and tissue injury. The exhaustion of antioxidant systems is one of the reasons for the occurrence of oxidative stress, which results in avalanche production of reactive oxygen species (ROS) or free radicals. High oxidative stress is common in organs and tissues with high metabolic and energy demands, including skeletal and heart muscle, liver and blood cells. Stress arises in animals in response to unavoidable or adverse environmental conditions. In the external environment, which affects the body of the cow, there are four main groups of stressors: physical, chemical, biological and psychological. Physical stressors include fluctuations in ambient temperature as well as mechanical injuries. High ambient temperature is one of the factors affecting the productivity of cows. Biological stressors are conditioned by errors and irregularities in habits. Both of these phenomena have an adverse impact on both the resistance of animals and fertility and are the etiological agent of oxidative stress. Various mechanisms may be responsible for metal‐induced oxidative stress: direct or indirect generation of ROS, depletion of glutathione and inhibition of antioxidant enzymes are well known for all redox‐active and redox‐inactive metals. © 2014 Society of Chemical Industry     

Protective effects of enzymatic digest from Ecklonia cava against high glucose‐induced oxidative stress in human umbilical vein endothelial cells

BACKGROUND: Antioxidants can prevent pathological damage caused by hyperglycaemia‐induced oxidative stress associated with diabetes. In the present study, we investigated whether the brown alga Ecklonia cava has protective effects against high glucose‐induced oxidative stress in Human umbilical vein endothelial cells (HUVECs). For that purpose, we prepared an enzymatic digest from E. cava (ECC) by using the carbohydrase, Celluclast. RESULTS: High glucose treatment induced HUVECs cell death, but ECC, at a concentration of 10 or 100 µg mL^?1, significantly inhibited the high glucose‐induced cytotoxicity. Furthermore, treatment with ECC dose‐dependently decreased thiobarbituric acid reactive substances (TBARS), intracellular generation of reactive oxygen species, and the nitric oxide level increased by high glucose. In addition, ECC treatment increased activities of antioxidant enzymes including catalase, superoxide dismutase and glutathione peroxidase in high‐glucose pretreated HUVECs. High glucose levels induced the overexpression of inducible nitric oxide synthase, cyclooxygenase‐2 and nuclear factor‐kappa B proteins in HUVECs, but ECC treatment reduced the overexpression of these proteins. CONCLUSION: These results suggest that ECC is a potential therapeutic agent that will reduce the damage caused by hyperglycaemia‐induced oxidative stress associated with diabetes. Copyright © 2009 Society of Chemical Industry     

Metabolomic analyses on microbial primary and secondary oxidative stress responses

Food safety is veryimportant in our daily life. In food processing or disinfection, microorganisms are commonly exposed to oxidative stress perturbations. However, microorganisms can adapt and respond to physicochemical interventions, leading to difficulty and complexity for food safety assurance. Therefore, understanding the response mechanisms of microbes and providing an overview of the responses under oxidative stress conditions are beneficial for ensuring food safety for the industry. The current review takes the metabolomics approach to reveal small metabolite signatures and key pathway alterations during oxidative stress at the molecular and technical levels. These alterations are involved in primary oxidative stress responses due to inactivation treatments such as using hypochlorite (HOCl), hydrogen peroxide (H₂O₂), electrolyzed water (EW), irradiation, pulsed light (PL), electron beam (EB), and secondary oxidative stress responses due to exposures to excessive conditions such as heat, pressure, acid, and alkaline. Details on the putative origin of exogenous or endogenous reactive oxygen species (ROS) are discussed, with particular attention paid to their effects on lipid, amino acid, nucleotide, and carbohydrate metabolism. In addition, mechanisms on counteracting oxidative stresses, stabilization of cell osmolality as well as energy provision for microbes to survive are also discussed.     

Sensitivity of antioxidant-deficient yeast to hypochlorite and chlorite

Sodium hypochlorite and sodium chlorite are commonly used as disinfectants, and understanding the mechanisms of microbial resistance to these compounds is of considerable importance. In this study, the role of oxidative stress and antioxidant enzymes in the sensitivity of the yeast Saccharomyces cerevisiae to hypochlorite and chlorite was studied. Yeast mutants lacking Cu-Zn superoxide dismutase, but not mutants deficient in cytoplasmic and peroxisomal catalase, were hypersensitive to the action of both hypochlorite and chlorite. Both compounds depleted cellular glutathione, induced the production of reactive oxygen species and decreased the viability of the cells. The toxicity of hypochlorite and chlorite was abolished by hypoxic and anoxic conditions and ameliorated by thiol antioxidants and ascorbate. The results demonstrated that the action of hypochlorite and chlorite involves the formation of superoxide and peroxide and that SOD1 is protective, probably by limiting the formation of hydroxyl radicals and damage to proteins.