Dov Lichtenberg

Tel Aviv University | TAU · Department of Physiology and Pharmacology

Multiple data are available on the self-assembly of mixtures of bilayer-forming amphiphiles, particularly phospholipids and micelle-forming amphiphiles, commonly denoted detergents. The structure of such mixed assemblies has been thoroughly investigated, described in phase diagrams, and theoretically rationalized in terms of the balance between the...

Although detergents are routine tools in biomembrane research, their use remains empirical. We propose that solubilization is the result of a balance between two parameters: (i) the energy associated with bending of phospholipid monolayers into a curved micellar surface, and (ii) the energy associated with filling the void in the center of the resu...

Peroxidation of lipids, particularly polyunsaturated fatty acid residues (PUFA) of phospholipids and cholesterol esters, is a process of marked implications: it shortens the shelf-life of food and drugs, it causes fragmentation of DNA, it damages cellular membranes and it promotes the genesis of many human diseases. Much effort is therefore devoted...

The steady-state redox status is physiologically important and therefore homeostatically maintained. Changes in the status result in signaling (eustress) or oxidative damage (distress). Oxidative stress (OS) is a hard-to-quantitate term that can be estimated only based on different biomarkers. Clinical application of OS, particularly for selective...

A redox steady state is important in maintaining vital cellular functions and is therefore homeostatically controlled by a number of antioxidative agents, the most important of which are enzymes. Oxidative Stress (OS) is associated with (or/and caused by) excessive production of damaging reactive oxygen and/or nitrogen species (ROS, RNS), which pla...

Goat milk is commonly used as a “grandmother’s drug” in traditional therapy of oral ulcers and lesions caused by Herpes Simplex Virus type 1 (HSV-1) infection without any basic scientific study. The aim of this study is to characterize and quantify the anti-viral effect of goat milk and its components against different viruses and to gain understan...

Recently, Weber et al. published a thorough investigation of the age-dependency of oxidative stress (OS) determined by the steady state concentrations of different compounds - oxidation products and antioxidants - that are in common use as biomarkers of OS in 2207 healthy individuals of the cross-sectional MARK-AGE Project. The correlations among b...

The commonly used term “oxidative stress” (OS) is intuitively defined as an excess of pro-oxidative compounds, over antioxidants. The redox status is homeostatically controlled because on one hand, pro-oxidants are essential for normal body function, whereas, on the other hand, pro-oxidants (and OS) are associated with many diseases due to the risk...

Aim: The meta-analysis was conducted to estimate of the cardiovascular benefits of indiscriminate supplementation of omega-3 capsules. The results, expressed in terms of quality adjusted life years (QALY) intuitively understood by the general public, can be the basis for the (personal) decision on whether to take omega-3 supplements. Methods: Th...

In spite of the great interest and intensive research, the actual mechanism of copper-induced peroxidation is debatable. The accepted paradigm is that the two step mechanism (r.1,r.2) can be ruled out because reaction r.1 is "thermodynamically unfavorable", the redox potential of LO2· (range 0.77 V - 1.44 V) being higher than the redox potential of...

LDL peroxidation plays a major role in many physiological and pathophysiological processes. The mechanisms of LDL peroxidation induced by transition metal ions have therefore been studied intensively. It has been proposed that the mechanism involves free radical production that occurs via decomposition of hydroperoxides. This, in turn, requires the...

The aim of the present study was to evaluate the apparent disagreement regarding the effect of a typical cycling progressive exercise, commonly used to assess V O 2 m a x , on the kinetics of ex vivo copper induced peroxidation of serum lipids. Thirty-two (32) healthy young men, aged 24–30 years, who do not smoke and do not take any food supplem...

In view of the complexity of biological membranes, the dependence of peroxidation on the physicochemical properties of membranes and on different antioxidants have been studied in liposomes made of different compositions, under different conditions. low molecular weight antioxidants and the dependence of these effects on various factors have also b...

Exercise-induced changes of the levels of OS biomarkers, dependencies on pre-exercise levels.

Most of the commonly used assays of oxidative stress (OS) are based on the level of the studied biomarker, as measured at one time-point. OS, as evaluated with different assays do not correlate with each other, so that OS cannot be defined in universal terms. Furthermore, some biomarkers are not very stable in withdrawn blood and their level may de...

The 30(th) birthday of a central concept in biomedicine, such as oxidative stress (OS) is a good time for re-evaluation of its contribution to science and particularly to the field of redox biology. In his recent communication, Sies described the history of the concept as well as the benefits and pitfalls of the term OS. In this mini-review, we dis...

In a previous study, we proposed characterizing the typically observed kinetic profiles of transition metal ion-induced lipid peroxidation in terms of a limited number of characteristic time-points. These time-points can be derived from experimental time-dependencies and be presented in terms of rate constants and concentrations as calculated based...

Antioxidants inhibit oxidation processes and by this affect many biological processes. This, in turn, promotes continuing efforts to synthesize new efficient antioxidants and discover compounds of natural origin capable of preventing peroxidation. Although many assays have been developed to evaluate antioxidants, the search for improved protocols i...

The commonly-accepted "oxidized LDL hypothesis of atherogenesis" is based on a large number of indi-rect evidence that shows that oxidatively-modified LDL plays a role in atherogenesis. Yet, the exact role is not clear. Some researchers think that oxidatively modi-fied biomolecules initiate atherogenesis; others be-lieve that they "only" promote th...

Various human diseases have been associated with lipid peroxidation, particularly the oxidation of polyunsaturated fatty acids (PUFAs). the bis-allylic CH2-groups in PUFAs are susceptible to hydrogen atom abstraction, making PUFAs prone to free radical-mediated peroxidation. Tocopherol typically serves as a chain-breaking antioxidant in free radica...

Abstract Physical exercise has many benefits, but it might also have a negative impact on the body, depending on the training level, length of workout, gender, age and fitness. The negative effects of physical exercise are commonly attributed to an imbalance between the levels of antioxidants (both low molecular weight antioxidants and antioxidant...

Solubilization of membranes by detergents, commonly described by phase diagrams, is an essential tool in membrane biochemistry and biophysics.In spite of its importance in assuring that the states of aggregation in lipid-detergent mixtures are at equilibrium, the mechanism(s) of solubilization proposed thus far are based on ambiguous analyses of in...

Urate is the major water-soluble low molecular weight antioxidants in serum, contributing about 50% to the antioxidative potential of the serum. Unexpectedly, both urate, as well as the other major antioxidant ascorbate, promote the copper-induced peroxidation of liposomal PUFA. In a previous study it has been shown that ascorbate inhibits copper-i...

Given the assumption that oxidative stress plays a pivotal role in atherogenesis, it could have been predicted that antioxidants will slow or even stop the development of atherotic plaques. The results of the latter prediction were disappointing. Moreover, previous meta-analyses concluded that indiscriminate supplementation of vitamin E at high dos...

Evaluation of the activity of antioxidants is commonly based on measurements of the effect of a specific antioxidant on redox reactions conducted in a solution. Given the difference between reactions that occur in homogeneous solutions and those that occur at lipid-water interfaces, as in biological membranes and lipoproteins, the relevance of the...

In spite of the growth of Israel's population, the number of graduates from the four Israeli Schools of Medicine has changed very little in the last 30 years. Nevertheless, the annual number of new practitioners grew from about 300 to 900, due to Israeli graduates of European Schools and the large number of physicians among the new immigrants from...

Fibrillization of amyloid polypeptides is accompanied by formation of reactive oxygen species (ROS), which, in turn, is assumed to further promote amyloid-related pathologies. Different polyphenols, all of which are established antioxidants, cause dissociation of amyloid fibrils. This study addresses the latter, poorly understood process. Specifica...

For many years, the prevailing concept was that LDL oxidation plays the central role in atherogenesis. As a consequence, supplementation of antioxidants, particularly vitamin E, became very popular. Unfortunately, major randomized clinical trials yielded disappointing results and recent meta-analyses concluded that indiscriminate, high dose vitamin...

Reactive oxygen species (ROS) are postulated to be a common trigger of insulin resistance. For example, treatment of adipocytes with either tumor-necrosis factor-alpha or dexamethasone increases ROS before impairing glucose uptake. Similarly, treatment with mitochondria-specific antioxidants preserves insulin sensitivity in animal models of insulin...

The distribution of phosphatidylcholine (PC) and sphingomyelin (SM) between the solubilized (micellar) and non-solubilized (lamellar) fractions arising from bilayers composed of PC and SM, with or without cholesterol (Chol) has been measured under conditions of partial, incomplete solubilization by Triton X-100. Quantitation is achieved by (31)P-NM...

For many years, the prevailing concept was that LDL oxidation plays a central role in atherogenesis. As a consequence, supplementation of antioxidants, particularly vitamin E, became very popular. Unfortunately, however, the major randomized clinical trials have yielded disappointing results on the effects of vitamin E on both mortality and morbidi...

Solubilization of bilayers made of sphingomyelin (SM) requires much less Triton X-100 (TR) than solubilization of bilayers made of phosphatidylcholine (PC). By apparent contrast, partial solubilization of biomembranes results in PC-rich mixed micelles, in which the SM/PC ratio is lower than 1.0, in coexistence with detergent-resistant membranes (DR...

The study was conducted to evaluate the diverse effect and clinical significance of TEST yolk buffer treatment on sperm samples of 128 infertile men. Sperm samples were incubated with TEST yolk buffer and control medium (Ham's F-10) at room temperature for 2 h. The hemizona indices (mean +/- SE) of the TEST yolk buffer and medium-treated sperm samp...

ABSTRACT— A two-stage study was carried out to characterize the bile and plasma lipid composition in normolipidemic non-obese patients with and without cholesterol gallstones. The first stage involved 11 patients with cholesterol gallstones admitted for elective cholecystectomy and a control group of 16 patients without cholesterol gallstones under...

Fibrillization of amyloid polypeptides is accompanied by formation of reactive oxygen species (ROS), which, in turn, is assumed to further promote amyloid-related pathologies. Different polyphenols, all of which are established antioxidants, cause dissociation of amyloid fibrils. This study addresses the latter, poorly understood process. Specifica...

Medical school admissions traditionally rely heavily on cognitive variables, with non-cognitive measures assessed through interviews only. In recognition of the unsatisfactory reliability and validity of traditional interviews, medical schools are increasingly exploring alternative approaches that can provide improved measures of candidates' person...

Celecoxib (Celebrex, Pfizer, NY, USA) is a worldwide top branded COX-2-specific inhibitor. It was shown to provide relief of arthritic pain and inflammation and has recently been under investigation for the prevention and treatment of cancer. However, recent studies showed that long term use of high doses of celecoxib is associated with an increase...

Copper-induced peroxidation of liposomal palmitoyllinoleoyl-phosphatidylcholine (PLPC) is inhibited by alpha-tocopherol at micromolar concentrations. In our previous study we found that when the liposomes contain phosphatidylserine (PS), nanomolar concentrations of Toc were sufficient to inhibit peroxidation. In an attempt to gain understanding of...

Oxidative damage has been linked to prostate carcinogenesis but its role in disease development and progression remains elusive. We investigated associations between indexes of oxidative stress with localized and advanced prostate cancer. Specifically we assessed the susceptibility of serum lipids to copper induced peroxidation (oxidizability). Ser...

This is a fascinating and popular account of the very large and the very small, from the universe as a whole to subatomic physics. It includes qualitative explanations of quantum mechanics and relativity, the big bang with inflation, the synthesis of elements, atoms, nuclei, subnuclear physics, quarks, leptons, and other elementary particles. It al...

Free radicals, formed via different mechanisms, induce peroxidation of membrane lipids. This process is of great importance because it modifies the physical properties of the membranes, including its permeability to different solutes and the packing of lipids and proteins in the membranes, which in turn, influences the membranes' function. Accordin...

Previous investigations demonstrated that various aromatic compounds, many of which are known antioxidants, inhibit amyloid fibril formation. Yet, the mechanism of action of these compounds is not fully understood and contribution of their antioxidative potency has not been addressed. In recent publications, Ono et al. (2003, 2004) studied the anti...

Lipid peroxidation is believed to play an important role in the pathogenesis of many diseases. Much research has therefore been devoted to peroxidation of different lipids in biomembranes and in model systems (liposomes) of different compositions. Yet, in spite of the relative simplicity of the liposomes, the existing literature is insufficient to...

In our previous studies we have shown that the process of term labor is associated with oxidative stress, as indicated by increased susceptibility of maternal serum lipids to copper induced peroxidation. In order to continue evaluating the role of oxidative stress in the labor process, we next tested whether term premature rupture of the membranes...

Introduction Lipid Analysis and Purity Characterization and Preparation of Liposomes Stability and Preservation Liposome Engineering: A User Guide List of Abbreviations

Osteoarthritis (OA) is the Western world's leading cause of disability. Cyclo-oxygenase-2 (COX-2) inhibitors are efficient anti-inflammatory agents commonly used in the treatment of osteoarthritis. However, recent studies have shown that their long-term use may be limited due to cardiovascular toxicity. The anti-inflammatory efficacy of the phytoch...

The objective of our study was to evaluate the effect of short-term intensive exercise on the susceptibility of serum lipids to ex-vivo peroxidation. We assessed the association between aerobic capacity, serum composition, and serum lipid oxidizability as well as the association between aerobic capacity and the effect of short-term maximal exercise...

Urate and ascorbate are the major water-soluble low molecular weight antioxidants in serum. Much attention has been devoted to the effect of these antioxidants on lipoprotein peroxidation in vivo and on their effect on copper-induced peroxidation ex vivo. These studies revealed that urate inhibits ascorbate oxidation in vitro, whereas the effect of...

Multiple studies have indicated that cyclooxygenase-2 (COX-2) inhibitors may prevent colon cancer, which is one of the leading causes of cancer death in the western world. Recent studies, however, showed that their long-term use may be limited due to cardiovascular toxicity. This study aims to investigate whether curcumin potentiates the growth inh...

Three originally distinct concepts - lipid rafts, detergent-resistant membranes (DRMs) and liquid-ordered (lo) lipid phases - are often confused in current literature; many researchers have assumed that all three names refer to the same chemico-biological entity. In fact, theoretical and experimental findings provide strong evidence against identif...

We tested whether neonates are subject to oxidative stress by comparing the susceptibility of umbilical blood lipids with copper-induced peroxidation. Umbilical arterial and venous blood samples were drawn from 32 pregnant women who delivered by elective cesarean section (CS) and from 32 pregnant women who delivered by spontaneous vaginal delivery...

Most of the studies on the solubilization of model membranes by Triton X-100 (TR) involve one lipid. The aim of the present study was to evaluate the effect of the addition of cholesterol on the solubilization of bilayers made of palmitoyloleoylphosphatidylcholine (POPC) or dipalmitoylphosphatidylcholine (DPPC). Detailed investigation of the kineti...

Oxidative modifications of LDL are involved in atherogenesis. Previously we have developed a simple assay to evaluate the susceptibility of lipids to copper-induced peroxidation in the relatively natural milieu of unfractionated serum in the presence of excess citrate. Based on our previous results we have proposed that the inducer of peroxidation...

Oxidative stress is a term used to denote the imbalance between the concentrations of reactive oxygen and nitrogen species and the defense mechanisms of the body. Although it is generally accepted that such an imbalance plays a pivotal role in many pathologies, the term "oxidative stress" remains ill defined. In an attempt to evaluate the relations...

Most of the studies on the solubilization of model membranes conducted thus far involved model membranes made of liquid-crystalline phospholipids. Relatively little is known on the influence of temperature and of the phase of the lipid bilayers on their solubilization by detergents. The aim of the present study was to gain knowledge about the tempe...

Peroxidation of membrane phospholipids is an important determinant of membrane function. Previously we studied the kinetics of peroxidation of the polyunsaturated fatty acid (PUFA) residues in model membranes (liposomes) made by sonication of palmitoyllinoleoylphosphatidylcholine (PLPC). Since most biomembranes are negatively-charged, we have now s...

In lipid oxidation kinetics studies, prevalent cardiovascular disease has been associated with shortened lag phase, the length of time preceding the onset of oxidation. To examine, in vitro, copper-induced lipid oxidation kinetics in unfractionated serum from hemodialysis patients and to determine differences in kinetic parameters between patients...

Several reports suggest preeclampsia to be associated with oxidative stress. In view of potential experimental artifacts in these studies, we tested the effect of preeclampsia on the oxidizibility of maternal serum lipids, using an optimized ex vivo method. This prospective study included 28 pregnant women with preeclampsia and 28 women matched for...

Previous studies have suggested that obesity enhances the inflammatory response, producing macromolecules involved in the induction and/or maintenance of increased erythrocyte aggregation. The objectives of this study were to evaluate the correlation between inflammation markers, erythrocyte adhesiveness/aggregation, and the degree of obesity and t...

Kinetic studies of copper-induced LDL peroxidation commonly assume that the availability of molecular oxygen in the reaction media is not a limiting factor. The present study reveals that this assumption is valid only at low LDL concentrations. At high LDL concentrations, accumulation of oxidation products, as monitored spectroscopically under cond...

As a first step towards evaluating the role of oxidative stress in the process of labour, we tested whether term labour is associated with increased oxidisibility of maternal serum lipids. A controlled prospective study. Tertiary care centre. Twenty healthy women in active labour and 20 healthy pregnant women not in labour (controls) matched for ma...

Peroxidation of blood lipoproteins is regarded as a key event in the development of atherosclerosis. Hence, attenuation of the oxidative modification of lipoproteins by natural and synthetic antioxidants in vivo is considered a possible way of prevention of cardiovascular disorders. The assessment of the susceptibility of lipoproteins to oxidation...

Micelle formation by many surfactants is endothermic at low temperatures but exothermic at high temperatures. In this respect, dissociation of micelles (demicellization) is similar to dissolving hydrocarbons in water. However, a remarkable difference between the two processes is that dissolving hydrocarbons is isocaloric at about 25 degrees C, almo...

In an attempt to deepen our understanding of the mechanisms responsible for lipoprotein peroxidation, we have studied the kinetics of copper-induced peroxidation of the polyunsaturated fatty acid residues in model membranes (small, unilamellar liposomes) composed of palmitoyllinoleoylphosphatidylcholine (PLPC). Liposomes were prepared by sonication...

Low-density lipoprotein (LDL) oxidation in the arterial intima plays a pivotal role in atherogenesis. Under physiologic conditions, several mechanisms protect LDL against oxidation, including hydrolysis of oxidation products by high-density lipoprotein (HDL)-associated enzymes. Some of these protective mechanisms are less effective under acute phas...

In view of the proposed central role of LDL oxidation in atherogenesis and the established role of HDL in reducing the risk of atherosclerosis, several studies were undertaken to investigate the possible effect of HDL on LDL peroxidation. Since these investigations yielded contradictory results, we have conducted systematic kinetic studies on the o...

Copper-induced peroxidation of lipoproteins involves continuous production of free radicals via a redox cycle of copper. Formation of Cu(I) during Cu(II)-induced peroxidation of LDL was previously demonstrated by accumulation of the colored complexes of Cu(I) in the presence of one of the Cu(I)-specific chelators bathocuproine (BC) or neocuproine (...

The phase behavior of mixtures of phospholipids and detergents in aqueous solutions is an issue of basic importance for understanding the solubilization and reconstitution of biological membranes. We review the existing knowledge on the compositionally induced reversible transformation of phospholipid bilayers into lipid-detergent mixed micelles. F...

The hydrolysis of cell membrane phospholipids by phospholipase A(2) (PLA(2)) leads to the production of numerous lipid mediators of diverse pathological conditions, mainly inflammatory diseases. These include lysophospholipids and their derivatives, and arachidonic acid and its derivatives (the eicosanoids). Both these groups of mediators are produ...

Comparison of the kinetic profiles of copper-induced peroxidation of HDL and LDL at different copper concentrations reveals that under all the studied experimental conditions HDL is more susceptible to oxidation than LDL. The mechanism responsible for HDL oxidation is a complex function of the copper/HDL ratio and of the tocopherol content of the H...

The amphiphilic polysaccharide hyaluronic acid-linked phosphatidylethanolamine (HyPE), synthesized by covalently binding dipalmitoyl-phosphatidylethanolamine (DPPE) to short chain hyaluronic acid (mol. wt. approximately = 30 000), interacts with low-density lipoproteins (LDL), to form a 'sugar-decoration' of the LDL surface. This results in an incr...

We consider the phase behavior of an aqueous solution of a mixture of two amphiphiles having different structural properties:  a phospholipid, which tends to self-assemble into extended flat bilayers forming closed vesicles, and a surfactant, which self-organizes into small, strongly curved micelles. In a mixture of the two amphiphiles, the two kin...

Excessive uptake of oxidized low density lipoprotein plays a role in the onset of atherosclerosis. Lipid-associated antioxidants, the most abundant of which is tocopherol (vitamin E), are therefore believed to have anti-atherogenic properties. By contrast, hydroperoxides enhance the peroxidation of low density lipoprotein. We demonstrate that none...

As a first step in evaluating the significance of our recently developed method of monitoring the kinetics of copper-induced oxidation in unfractionated serum, we recorded the kinetics of lipid oxidation in the sera of 62 hyperlipidemic patients and analyzed the correlation between oxidation and lipid composition of the sera [high density lipoprote...

Phosphotipase A2 (PLA2) was used to hydrolyze phosphatidylcholine (PC) in microemulsions. Phase diagrams were constructed for mixtures of alcohols (C2-C6), medium chain triglycerides (tricaprylin, TC) or vegetable oils, PC and water, and areas corresponding to isotropic systems were identified. The PC hydrolysis was carried out with high yields at...