Lipid Peroxidation In Biological Membranes Research Articles

Graphene Quantum Dots Inhibit Lipid Peroxidation in Biological Membranes.

Excessive reactive oxygen species (ROS) in cellular environments leads to oxidative stress, which underlies numerous diseases, including inflammatory diseases, neurodegenerative diseases, cardiovascular diseases, and cancer. Oxidative stress can be particularly damaging to biological membranes such as those found in mitochondria, which are abundant with polyunsaturated fatty acids (PUFAs). Oxidation of these biological membranes results in concomitant disruption of membrane structure and function, which ultimately leads to cellular dysfunction. Graphene quantum dots (GQDs) have garnered significant interest as a therapeutic agent for numerous diseases that are linked to oxidative stress. Specifically, GQDs have demonstrated an ability to protect mitochondrial structure and function under oxidative stress conditions. However, the fundamental mechanisms by which GQDs interact with membranes in oxidative environments are poorly understood. Here, we used C11-BODIPY, a fluorescent lipid oxidation probe, to develop quantitative fluorescence assays that determine both the extent and rate of oxidation that occurs to PUFAs in biological membranes. Based on kinetics principles, we have developed a generalizable model that can be used to assess the potency of antioxidants that scavenge ROS in the presence of biological membranes. By augmenting our fluorescence assays with 1H NMR spectroscopy, the results demonstrate that GQDs scavenge nascent hydroxyl and peroxyl ROS that interact with membranes and that GQDs are potent inhibitors of ROS-induced lipid oxidation in PUFA-containing biological membranes. The antioxidant potency of GQDs is comparable to or even greater than established antioxidant molecules, such as ascorbic acid and Trolox. This work provides mechanistic insights into the mitoprotective properties of GQDs under oxidative stress conditions, as well as a quantitative framework for assessing antioxidant interactions in biological membrane systems.

Indicators of lipid peroxidation of biological membranes in patients with COVID-19

Indicators of lipid peroxidation of biological membranes in patients with COVID-19

Liposomes embedded with PEGylated iron oxide nanoparticles enable ferroptosis and combination therapy in cancer.

Ferroptosis, an iron-dependent regulated cell death process driven by excessive lipid peroxides, can enhance cancer vulnerability to chemotherapy, targeted therapy and immunotherapy. As an essential upstream process for ferroptosis activation, lipid peroxidation of biological membranes is expected to be primarily induced by intrabilayer reactive oxygen species (ROS), indicating a promising strategy to initiate peroxidation by improving the local content of diffusion-limited ROS in the lipid bilayer. Herein, liposomes embedded with PEG-coated 3nm γ-Fe2O3 nanoparticles in the bilayer (abbreviated as Lp-IO) were constructed to promote the intrabilayer generation of hydroxyl radicals (•OH) from hydrogen peroxide (H2O2), and the integration of amphiphilic PEG moieties with liposomal bilayer improved lipid membrane permeability to H2O2 and •OH, resulting in efficient initiation of lipid peroxidation and thus ferroptosis in cancer cells. Additionally, Lp-IO enabled traceable magnetic resonance imaging and pH/ROS dual-responsive drug delivery. Synergistic antineoplastic effects of chemotherapy and ferroptosis, and alleviated chemotherapeutic toxicity, were achieved by delivering doxorubicin (capable of xCT and glutathione peroxidase inhibition) with Lp-IO. This work provides an efficient alternative for triggering therapeutic lipid peroxidation and a ferroptosis-activating drug delivery vehicle for combination cancer therapies.

The physiological insight of Coenzyme-Q10 administration in preventing the incidence of reperfusion arrhythmia among patients undergoing coronary artery bypass grafting surgery.

Reperfusion arrhythmia following cardiac surgery has long been studied as part of myocardial damage. Reperfusion injury is thought to be exacerbated by oxygen-free radicals, whereas arrhythmogenic oscillations in membrane potential are mediated by reactive oxygen. Coenzyme Q10 is a lipid-soluble antioxidant that inhibits lipid peroxidation in biological membranes and supplies ATP cell synthesis, required as the organism's primary energy source. This process explains how Coenzyme Q10 helps stabilize membranes and avoids critical metabolite depletion that may relate to reperfusion arrhythmia. There is a reduction of iatrogenic Coenzyme Q10 after coronary artery bypass surgery (CABG). On the other hand, there is an increased inflammatory process and cellular demand post CABG procedure. It leads to ischemia that can be manifested as arrhythmia. Reperfusion arrhythmia was less common in patients who took Coenzyme Q10. These findings suggest that Coenzyme Q10 supplementation might help patients with heart surgery avoid reperfusion arrhythmia. However, a higher-quality randomized controlled study is needed to determine the effect of Coenzyme Q10 in preventing reperfusion arrhythmia in cardiac surgery patients.

Regulatory System of Lipid Peroxidation as a Basis for Ecological Testing

Model systems were proposed, using previously obtained experimental data, for investigating the mechanism of regulation of oxidative processes in lipids isolated from natural objects, preparations, and various components of aqueous medium. The models include low-temperature oxidation of methyl oleate in a thin layer as a model system of lipid peroxidation in biological membranes; computer simulation to determine the involvement of lipids and biologically active substances at different stages of autoxidation; and model of spontaneous autoxidation of lecithin in aqueous solution to assess the ability of aqueous medium components to participate in the regulation of oxidative processes in biological systems.

Indices of peroxidation of lipids of biological membranes and endogenous intoxication in patients with psoriasis on the background of chronic viral hepatitis С

Aim. To study the features of lipid peroxidation of biological membranes and accumulation of toxic metabolites in the body of patients with psoriasis, depending on the presence of concomitant chronic viral hepatitis C.Materials and methods. In the survey, participated 56 patients with a vulgar form of psoriasis who received in-patient treatment at the Nalchik skin clinic in 2016–2017, divided into 2 groups, depending on the presence of concomitant chronic viral hepatitis C. In patients, the content of malonic dialdehyde in blood was determined as an indicator of the state of the prooxidant system, ceruloplasmin and erythrocyte catalase, as indicators of antioxidant protection, and also for the evaluation of the Intoxication Syndrome; the level of substances of low and medium molecular mass and oligopeptides in the biological environments of the organism in different periods of the disease.Results. It was found that the presence of concomitant chronic viral hepatitis C in patients with psoriasis was characterized by a more pronounced increase in the concentration of lipid peroxidation products than in the group of patients with hepatitis without psoriasis, accompanied by a decrease in the activity of antioxidant enzymes in the blood plasma and an increase in the activity of catalase in erythrocytes. Simultaneously, the presence of chronic hepatitis C led to a significantly higher content in the body fluids of patients with low and medium molecular weight substances and oligopeptides.

Novel antioxidant capacity assay for lipophilic compounds using electron paramagnetic resonance spectroscopy.

A novel antioxidant capacity assay for lipophilic compounds was developed using electron paramagnetic resonance (EPR) spectroscopy. The assay is based on antioxidant’s scavenging ability against the tert-butoxyl radical generated photolytically from di-tert-butyl peroxide in ethyl acetate, and named the tert-butoxyl-based antioxidant capacity (BAC) assay. The radical was trapped by spin trap, 5,5-dimethyl-1-pyrroline-N-oxide, and EPR signal intensity of the spin adduct was used as a quantitative marker of radical levels. Signal intensity decreased in a dose-dependent manner in the presence of an antioxidant that competitively reacts with the radical, which was utilized to evaluate BAC values.The BAC method enabled the accurate estimation of antioxidant capacity for lipophilic materials that may counteract lipid peroxidation in biological membranes. The BAC values for quercetin and caffeic acid are 0.639 ± 0.020 and 0.118 ± 0.012 trolox equivalents, respectively, which are much smaller than values obtained by other aqueous methods such as H-ORAC and ORAC-EPR. Thus, antioxidants present in a non-aqueous environment should be evaluated using a non-aqueous system. In combination with in situ ascorbate reduction, the BAC method was capable of accurately determining the antioxidant capacity of water-insoluble materials that may be reduced in living cells.

Вплив гепатомаксу на фертильність чоловіків

The features of morphotype sperm in men with infertility and found some monomodal its deviations. The study of products of lipid peroxidation (LPO) and antioxidant enzymes (AOP) levels in men with mild forms of chronic inflammation of the urogenital tract complicated with infertility. The studies found that the majority of men surveyed marked activation of lipid peroxidation of biological membranes, which was accompanied by increased concentrations of the major metabolite of LPO--intermediate (conjugated diene) and final (malondialdehyde) in serum. In the study of the system of AOP was found that the activity of catalase and superoxide dismutase decreased. Was calculated as an integrative index F, which characterizes the ratio of prooxidant and antioxidant properties of blood. Found suppression of the index, which indicates an imbalance indicators LPO/AOP. A negative correlation between the index F and the presence of mikrosomatich form sperm was found. The positive influence of the Hepatomax on the process of recovery oxidative activity systems, normalization of the integral index of F and reduce the number of abnormal forms of generative cells was established. Given antioxidant, immunomodulating, hepatoprotective properties of the Hepatomax, we consider it appropriate to include this drug in treatment of infertile men with inflammatory processes in the urogenital tract.

Five Decades with Polyunsaturated Fatty Acids: Chemical Synthesis, Enzymatic Formation, Lipid Peroxidation and Its Biological Effects

I have been involved in research on polyunsaturated fatty acids since 1964 and this review is intended to cover some of the most important aspects of this work. Polyunsaturated fatty acids have followed me during my whole scientific career and I have published a number of studies concerned with different aspects of them such as chemical synthesis, enzymatic formation, metabolism, transport, physical, chemical, and catalytic properties of a reconstructed desaturase system in liposomes, lipid peroxidation, and their effects. The first project I became involved in was the organic synthesis of [1-14C] eicosa-11,14-dienoic acid, with the aim of demonstrating the participation of that compound as a possible intermediary in the biosynthesis of arachidonic acid “in vivo.” From 1966 to 1982, I was involved in several projects that study the metabolism of polyunsaturated fatty acids. In the eighties, we studied fatty acid binding protein. From 1990 up to now, our laboratory has been interested in the lipid peroxidation of biological membranes from various tissues and different species as well as liposomes prepared with phospholipids rich in PUFAs. We tested the effect of many antioxidants such as alpha tocopherol, vitamin A, melatonin and its structural analogues, and conjugated linoleic acid, among others.

A synopsis of the process of lipid peroxidation since the discovery of the essential fatty acids

Eighty years ago, Burr and Burr, introduced for the first time the concept of essential fatty acids. Now is very well known that requirements for polyunsaturated fatty acids PUFAs can not be met by de novo metabolic processes within mammalian tissues. Animals are absolutely dependent on plants for providing the two major precursors of the n-6 and n-3 fatty acids, C18:2n-6; linoleic and C18:3n-3; α-linolenic acids. In animal tissues these precursors are transformed to fatty acids containing three to six double bonds. During the last four decades the interest in polyunsaturated fatty acids has augmented manifolds, and the number of published studies is rising each year. The current impetus for this interest has been mainly the observation that PUFAs and their metabolites have several physiological roles including: energy provision, membrane structure, cell signaling and regulation of gene expression. In addition the observation that PUFAs are targets of lipid peroxidation opens a new important area of investigation. Melatonin, the main secretory product of the pineal gland, efficiently scavenges both the hydroxyl and peroxyl radicals counteracting lipid peroxidation in biological membranes. In addition the two key pineal biochemical functions, lipoxygenation and melatonin synthesis may be synergistically regulated by the status of n-3 essential fatty acids. At the retina level, free radicals may preferentially react with the membrane polyunsaturated fatty acids leading to the release of lipoperoxide radicals. These lipoperoxides can induce oxidative stress linked to membrane lysis, damage to neuronal membranes may be related to alteration of visual function.

Quantum chemical and magnetic resonance studies on interaction of α-tocopherol with phospholipids

α-tocopherol constitutes the major component of Vitamin E and is most active in preventing lipid peroxidation in biological membranes. The interaction of α-tocopherol with phospholipid molecules has been investigated by the quantum chemical POLO method. The results indicate that the hydroxyl group of α-tocopherol is involved in binding with the phosphate group of the phospholipid through intermolecular hydrogen bonding. Experimental studies using proton and phosphorus-31 NMR spectroscopy have also been carried out on the binding of α-tocopherol with the phospholipid DPPC, and the results obtained are in agreement with those from the theoretical studies.

The cold but not hard fats in ectotherms: consequences of lipid restructuring on susceptibility of biological membranes to peroxidation, a review

The production of reactive oxygen species is a regular feature of life in the presence of oxygen. Some reactive oxygen species possess sufficient energy to initiate lipid peroxidation in biological membranes, self-propagating reactions with the potential to damage membranes by altering their physical properties and ultimately their function. Two of the most prominent patterns of lipid restructuring in membranes of ectotherms involve contents of polyunsaturated fatty acids and ratios of the abundant phospholipids, phosphatidylcholine and phosphatidylethanolamine. Since polyunsaturated fatty acids and phosphatidylethanolamine are particularly vulnerable to oxidation, it is likely that higher contents of these lipids at low body temperature elevate the inherent susceptibility of membranes to lipid peroxidation. Although membranes from animals living at low body temperatures may be more prone to oxidation, the generation of reactive oxygen species and lipid peroxidation are sensitive to temperature. These scenarios raise the possibility that membrane susceptibility to lipid peroxidation is conserved at physiological temperatures. Reduced levels of polyunsaturated fatty acids and phosphatidylethanolamine may protect membranes at warm temperatures from deleterious oxidations when rates of reactive oxygen species production and lipid peroxidation are relatively high. At low temperatures, enhanced susceptibility may ensure sufficient lipid peroxidation for cellular processes that require lipid oxidation products.

Selenium uptake and its influence on the antioxidative system of white clover as affected by lime and phosphorus fertilization

Selenium (Se) is regarded as an antioxidant in animal and human nutrition, but its biological role in plants needs to be clarified. Plants vary considerably in their ability to tolerate Se, and their biochemical response to Se may be affected by liming or P fertilization. Two greenhouse experiments were conducted with white clover (Trifolium repens L.) to evaluate Se accumulation, tolerance, and the antioxidant response at increasing selenite supply levels (from 0 to 60 g Se ha−1) and the effect of lime and P on both the Se uptake and the antioxidant activity of plants treated with 0, 20 and 40 g Se ha−1. Selenium concentration in plant tissues was increased by Se applications, and plant growth was reduced at Se supply levels above 20 g ha−1. At shoot concentration up to 200 μg kg−1 DW, Se promoted antioxidant ability by increasing the free radical scavenging activity and by inhibiting lipid peroxidation (TBARS), whereas above this level TBARS accumulation increased. Significant changes in the activities of peroxidase (POD) and ascorbate peroxidase (APX) enzymes were also observed as a consequence of the increase in shoot Se concentration. The application of lime and P improved the plant nutrition, which increased the dry matter yield and enhanced the plant’s antioxidative system. Under different combinations of soil acidity and P fertilization a differential uptake of Se by the plant occurred. These factors appear to be responsible for beneficial or detrimental effects of Se in terms of lipid peroxidation of biological membranes and the activation of POD and APX in white clover.

The Ability of Melatonin to Counteract Lipid Peroxidation in Biological Membranes

This paper reviews recent data relevant to the antioxidant effects of melatonin with special emphasis on the changes produced in polyunsaturated fatty acids located in the phospholipids of biological membranes. The onset of lipid peroxidation within cellular membranes is associated with changes in their physicochemical properties and with the impairment of protein functions located in the membrane environment. All cellular membranes are especially vulnerable to oxidation due to their high concentration of polyunsaturated fatty acids. These processes combine to produce changes in the biophysical properties of membranes that can have profound effects on the activity of membrane-bound proteins. This review deals with aspects for lipid peroxidation of biological membranes in general, but with some emphasis on changes of polyunsaturated fatty acids, which arise most prominently in membranes and have been studied extensively in our laboratory. The article provides current information on the effect of melatonin on biological membranes, changes in fluidity, fatty acid composition and lipid-protein modifications during the lipid peroxidation process of photoreceptor membranes and modulation of gene expression by the hormone and its preventive effects on adriamycin-induced lipid peroxidation in rat liver. Simple model systems have often been employed to measure the activity of antioxidants. Although such studies are important and essential to understand the mechanisms and kinetics of antioxidant action, it should be noted that the results of simple in vitro model experiments cannot be directly extrapolated to in vivo systems. For example, the antioxidant capacity of melatonin, one of the important physiological lipophilic antioxidants, in solution of pure triglycerides enriched in omega-3 polyunsaturated fatty acids is considerably different from that in subcellular membranes.

Determination of Lipid Peroxidation in Desiccated Red Blood Cells

Lipid peroxidation of biological membranes is one of the most studied indicators of oxidative stress. Very little is known about the extent of oxidative damage that occurs during the desiccation of mammalian cells. The objective of this study was to modify and validate a method for the determination of lipid peroxidation in desiccated red blood cells (RBCs). The measurement of malondialdehydes (MDAs), the decomposition products of oxidized polyunsaturated fatty acids, is commonly used as a method for the quantification of lipid peroxidation. The method is based on the reaction of MDAs with thiobarbituric acid, which forms a thiobarbituric acid reactive substances (TBARS) chromophore. Validation of the method to dried RBC specimens included the optimization of an MDA standard curve, spiking studies, measurement of TBARS in lyophilized RBCs, and reexamination of the reagents and processes that are associated with this assay. The recovery of MDA standards, which were lyophilized with RBCs was reasonable (72....

A New Role of Phosphoglucose Isomerase. Involvement of the Glycolytic Enzyme in Aldehyde Metabolism

Lipid peroxidation in biological membranes is accompanied by malonic dialdehyde (MDA) formation, but the problem of its further metabolism in cytoplasm remains unsolved. The experimental data obtained in this work showed that the liver fraction prepared by centrifugation at 10,000g contained phosphoglucose isomerase and enzymes of the glyoxalase system. In this fraction in the presence of GSH there is an aggregate of reactions taking place both in membranes (lipid peroxidation) and outside membranes (MDA conversion to methylglyoxal and further to neutral D-lactate). This means that MDA is slowly accumulated because it is a substrate of aldehyde isomerase (MDA <--> methylglyoxal). Most probably, phosphoglucose isomerase serves as this enzyme. We concluded that D-lactate should be regarded as the end product of two different parametabolic reactions: lipid peroxidation or protein glycation.

Direct evidence of singlet molecular oxygen [O2(1Deltag)] production in the reaction of linoleic acid hydroperoxide with peroxynitrite.

Peroxynitrite (ONOO-), a biologically active species, can induce lipid peroxidation in biological membranes, thereby leading to the formation of various hydroperoxides. We report herein on the formation of singlet molecular oxygen [O(2) ((1)Delta(g))] in the reaction of peroxynitrite with linoleic acid hydroperoxide (LAOOH) or (18)O-labeled LAOOH. The formation of O(2) ((1)Delta(g)) was characterized by (i) dimol light emission in the red spectral region (lambda > 570 nm) using a red-sensitive photomultiplier; (ii) monomol light emission in the near-infrared region (lambda = 1270 nm) with a liquid nitrogen-cooled germanium diode or a photomultiplier coupled to a monochromator; (iii) the enhacing effect of deuterium oxide on chemiluminescence intensity, as well as the quenching effect of sodium azide; and (iv) chemical trapping of O(2) ((1)Delta(g)) or (18)O-labeled O(2) ((1)Delta(g)) with the 9,10-diphenylanthracene (DPA) and detection of the corresponding DPAO(2) or (18)O-labeled DPA endoperoxide by HPLC coupled to tandem mass spectrometry. Moreover, the presence of O(2) ((1)Delta(g)) was unequivocally demonstrated by a direct spectral characterization of the near-infrared light emission attributed to the transition of O(2) ((1)Delta(g)) to the triplet ground state. For the sake of comparison, O(2) ((1)Delta(g)) deriving from the thermolysis of the endoperoxide of 1,4-dimethylnaphthalene or from the H(2)O(2)/hypochlorite and H(2)O(2)/molybdate systems were also monitored. These novel observations identified the generation of O(2) ((1)Delta(g)) in the reaction of LAOOH with peroxynitrite, suggesting a potential O(2) ((1)Delta(g))-dependent mechanism that contributes to cytotoxicity mediated by lipid hydroperoxides and peroxynitrite reactions in biological systems.

Distribution of coenzyme Q homologues in brain.

Ubiquinone (coenzyme Q10), in addition to its function as an electron and proton carrier in mitochondrial electron transport coupled to ATP synthesis, acts in its reduced form (ubiquinol) as an antioxidant, inhibiting lipid peroxidation in biological membranes and protecting mitochondrial inner-membrane proteins and DNA against oxidative damage accompanying lipid peroxidation. Tissue ubiquinone levels are subject to regulation by physiological factors that are related to the oxidative activity of the organism: they increase under the influence of oxidative stress, e.g. physical exercise, cold adaptation, thyroid hormone treatment, and decrease during aging. In the present study, coenzyme Q homologues were separated and quantified in the brains of mice, rats, rabbits, and chickens using high-performance liquid chromatography. In addition, the coenzyme Q homologues were measured in cells such as NG-108, PC-12, rat fetal brain cells and human SHSY-5Y and monocytes. In general, Q1 content was the lowest among the coenzyme homologues quantified in the brain. Q9 was not detectable in the brains of chickens and rabbits, but was present in the brains of rats and mice. Q9 was also not detected in human cell lines SHSY-5Y and monocytes. Q10 was detected in the brains of mice, rats, rabbits, and chickens and in cell lines. Since both coenzyme Q and vitamin E are antioxidants, and coenzyme Q recycles vitamins E and C, vitamin E was also quantified in mice brain using HPLC-electrochemical detector (ECD). The quantity of vitamin E was lowest in the substantia nigra compared with the other brain regions. This finding is crucial in elucidating ubiquinone function in bioenergetics; in preventing free radical generation, lipid peroxidation, and apoptosis in the brain; and as a potential compound in treating various neurodegenerative disorders.

Identification and Quantification of Phosphatidylethanolamine-Derived Glucosylamines and Aminoketoses from Human Erythrocytes—Influence of Glycation Products on Lipid Peroxidation

While the Maillard reaction of amino acids and proteins as well as its consequences in vivo has been thoroughly investigated, little attention has so far been paid to the glycation of aminophospholipids such as phosphatidylethanolamine (PE) or phosphatidylserine (PS), which are essential for structure and functionality of biological membranes. PE-derived glucosylamines (Schiff-PEs) and aminoketoses (Amadori-PEs) have now for the first time been simultaneously identified and quantified in erythrocytes from diabetics and healthy individuals by liquid chromatography–electrospray mass spectrometry (LC-(ESI)MS). The amounts of glycated PE (gPE) were significantly higher in diabetics (0.18–34.2 mol% Schiff-PE and 0.047–0.375 mol% Amadori-PE) than in controls (0.12–3.99 mol% Schiff-PE and 0.018–0.055 mol% Amadori-PE). A positive correlation between fructosylated hemoglobin (HbA1c) and the gPE levels was established. No advanced glycation endproducts (AGEs) like 5-hydroxymethylpyrrole-2-carbaldehyde (pyrrole-PE), carboxymethyl (CM-PE), or carboxyethyl (CE-PE) derivatives were detected. To investigate the influence of gPE on lipid peroxidation of biological membranes, liposomes consisting of soy-PE and synthetically prepared Amadori-PE (16:0–16:0) were incubated for several days and the formation of oxidation products was monitored. It could be shown that Amadori-PE extensively promotes lipid peroxidation even in the absence of transition metal ions like Cu2+ and Fe3+. Oxidative damage to membrane lipids therefore is supposed to be at least partially caused by the glycation of aminophospholipids.

Iron-induced oxidant stress leads to irreversible mitochondrial dysfunctions and fibrosis in the liver of chronic iron-dosed gerbils. The effect of silybin.

Hepatic iron toxicity because of iron overload seems to be mediated by lipid peroxidation of biological membranes and the associated organelle dysfunctions. However, the basic mechanisms underlying this process in vivo are still little understood. Gerbils were dosed with weekly injections of iron-dextran alone or in combination with sylibin, a well-known antioxidant, by gavage for 8 weeks. A strict correlation was found between lipid peroxidation and the level of desferrioxamine chelatable iron pool. A consequent derangement in the mitochondrial energy-transducing capability, resulting from a reduction in the respiratory chain enzyme activities, occurred. These irreversible oxidative anomalies brought about a dramatic drop in tissue ATP level. The mitochondrial oxidative derangement was associated with the development of fibrosis in the hepatic tissue. Silybin administration significantly reduced both functional anomalies and the fibrotic process by chelating desferrioxamine chelatable iron.