Surface active properties of isobornylphenols in systems with different degrees of complexity

Interrelations between the structure of the semi-synthetic phenolic antioxidants — isobornylphenols and their surface active properties were studied in the chemical (the lecithin aggregation in hexane) and biological (the incubation with the blood erythrocytes) model systems. It has been shown that all studied compounds are able to affect the lecithin aggregation in hexane: the share of the main fraction of the L micelles decreases with increasing the share of particles of greater size. The effect substantially depends on hindered OH group and the presence of the intramolecular hydrogen bond in molecule. The cytotoxic properties of isobornylphenols (the concentration is 100 μM) are predominantly due to the molecule structure. The interrelation between the aggregate size of the main fraction of L in the presence of the studied compounds and the discocyte share during mice blood erythrocyte incubation in their presence for 4 h is revealed. Thus, this provides the possibility to assume that the ability of the different biological active substances to affect the lecithin aggregation in non-polar solvent could be used as a model system for the initial assessment of their surface active properties.     

Antioxidative activity of some quaternary ammonium salts incorporated into erythrocyte membranes

The antioxidative activity of two series of amphiphilic compounds from a group of quaternary ammonium salts has been investigated. They were so-called bifunctional surfactants synthesized to be used as common pesticides or as antioxidants. The latter application was to be ensured by providing the compounds studied with an antioxidant group. Studies on antioxidative possibilities of those compounds were performed on pig erythrocytes. Due to their hydrophobic parts, they anchor in the erythrocyte membrane and influence the degree of lipid oxidation in the erythrocyte membrane subjected to UV radiation. It was found that compounds of both series decreased the oxidation of the membrane lipids. The inhibition of this oxidation increased with the length of their hydrophobic chains up to fourteen carbon atoms. The compounds of the longest hydrophobic chains showed a somewhat weaker antioxidative activity. Of the two series studied compounds were more effective having bromide ions as counterions. The corresponding compounds of a second series (chlorides) protected erythrocyte significantly weaker against oxidation. The effect of the compounds on fluidity of the erythrocyte membrane has been studied in order to explain the oxidation results. Change in fluidity of the erythrocyte ghost membranes was found also dependent on length of the hydrophobic part of the compounds and was more pronounced in the case of bromide surfactants. The final conclusion is that the compounds studied can be succesfully used as antioxidant agents of good efficacy.     

New aminophosphonates with antioxidative activity.

The antioxidative activity of some newly synthesized aminomethanephosphonic acid derivatives was studied. The compounds studied differed in their polarity and the hydrophobicity of the electronic substituents at their nitrogen and phosphorus atoms. It was found that all the aminophosphonates studied, both cyclic and acyclic, protected erythrocyte membranes against peroxidation to some extent. The effect was somewhat weaker in the case of cyclic compounds, and for erythrocytes irradiated with UV light. The cyclic compounds provided no protection of erythrocytes illuminated by natural light. The observed differences between the antioxidative activities of cyclic and acyclic compounds are probably related to differences in their ability to incorporate into the lipid phase of erythrocyte membranes. Once incorporated, they change the fluidity of the membranes. The extent of those changes was determined in fluorescence measurements. Generally, they were found to be more pronounced in the case of acyclic aminophosphonates, although as regards other structural differences between particular aminophosphonates, a clear picture of the relationship between structure and effect is more difficult to obtain. No correlation was found between the antioxidative efficiency of the compounds and the fluidity changes they induce.     

Antioxidative activity of some phenoxy and organophosphorous compounds

Experiments were performed in order to check whether biological activity of some organophosphorous compounds widely applied as herbicides: 2,4-dichlorophenoxyacetic acid (1) and its sodium salt (2), N-phosphonomethylglycine acid (3) and its sodium salt (4), diethyl 1-butylamino-1-cyclohexanephosphonate (5) and diethyl 9-butylamino-9-fluorenephosphonate (6) followed from their oxidative activity. The compounds studied differed in their polarity and hydrophobicity. On the contrary, it was found that all herbicides protected erythrocyte membranes against partial peroxidation induced by UV irradiation. The effect was somewhat differentiated and followed the sequence: 5 >1 >2 >6 >3 >4. The observed differences between the antioxidative activities of the compounds are probably related to differences in their ability to incorporate into the lipid phase of the erythrocyte membrane. Once incorporated, they change fluidity of the membranes. The extent of the changes was determined in fluorescence measurements. Polarization and anisotropy coefficients of erythrocyte membranes modified by micromolar concentrations of herbicides at different temperatures were measured for that purpose. Generally, they followed the sequence found for antioxidative activity of the herbicides studied, which confirms the assumption of close correlation between the depth of incorporation of a herbicide into the erythrocyte membrane and its protective efficiency.     

Effect of some nickel compounds on red blood cell characteristics

The effect of certain inorganic and coordinated nickel compounds on the resistance to different destructive substances, rheological properties, and functional activity of healthy human red blood cells (RBC), was investigated. It is shown that nickel compounds affect the erythrocyte membrane lipid bilayer, as well as membrane proteins to various extents, depending on the type of compounds used. In general, the acceleration of erythrocyte aging was observed to be more pronounced in young erythrocytes. The observed results suggest that nickel compounds decrease water permeability across erythrocyte membranes. Almost all the investigated nickel compounds decrease erythrocyte thermostability, deformability, and the rate of O₂ release by erythrocytes.     

Synthesis of novel terpenophenol-chlorin conjugates and evaluation of their membranotropic and membrane-protecting properties

A series of conjugates has been synthesized by the reaction of methylpheophorbide a with ortho-alkylaminomethyl derivatives of 2-isobornyl-4-methylphenol; the terpenophenol fragment in the conjugates is attached to the methylpheophorbide a macrocycle by an amide bond formed upon the amidation of the 13(2)-ester group. A scanning electron microscopy study of the surface structure of erythrocytes incubated with these compounds confirmed their ability to interact with the cell membrane. It was found, based on the ability of the conjugates to inhibit the H₂O₂-induced hemolysis of erythrocytes and slow down the accumulation of the secondary lipid peroxidation products, that they possess membrane-protecting and antioxidant properties.     

The role of interspecies differences in the ratio of choline-containing phospholipid fractions of rodent erythrocytes in response of these cells to the effect of membranotropic compounds

In in vitro experiments, interspecies differences were revealed in the erythrocyte responses in varied rodent species—laboratory mice (Mus musculus L.), tundra voles (Microtus oeconomus Pall.) and bank voles (Myodes glareolus Pall.)—to the effect of chemical agents able to interact with membrane lipids and disrupt the membrane structure (detergent Triton X-100, oxidative stress inductor AAPH, antioxidant ionol or BHT, uranyl ion). It was hypothesized that these differences are due to physicochemical peculiarities of the erythrocyte membrane structure, specifically, the ratio of choline-containing fractions of phospholipids (phosphatidylcholine and sphingomyelin). The use of blood erythrocytes as an in vitro experimental model to study the mechanisms of toxicity as well as antioxidant and membrane-protective properties of compounds of different nature was shown to imply the choice of an adequate source of erythrocytes in view of considerable speciesdependent structural specificity of the lipid component of mammalian erythrocyte membranes.     

Acetylsalicylic acid (aspirin) and salicylic acid interaction with the human erythrocyte membrane bilayer induce in vitro changes in the morphology of erythrocytes

Despite the well-documented information, there are insufficient reports concerning the effects of salicylate compounds on the structure and functions of cell membranes, particularly those of human erythrocytes. With the aim to better understand the molecular mechanisms of the interaction of acetylsalicylic acid (ASA) and salicylic acid (SA) with cell membranes, human erythrocyte membranes and molecular models were utilized. These consisted of bilayers of dimyristoylphosphatidylcholine (DMPC) and dimyristoylphosphatidylethanolamine (DMPE), representative of phospholipid classes located in the outer and inner monolayers of the human erythrocyte membrane, respectively. The capacity of ASA and SA to perturb the multibilayer structures of DMPC and DMPE was evaluated by X-ray diffraction while DMPC unilamellar vesicles (LUV) were studied by fluorescence spectroscopy. Moreover, we took advantage of the capability of differential scanning calorimetry (DSC) to detect the changes in the thermotropic phase behavior of lipid bilayers resulting from ASA and SA interaction with PC and PE molecules. In an attempt to further elucidate their effects on cell membranes, the present work also examined their influence on the morphology of intact human erythrocytes by means of defocusing and scanning electron microscopy, while isolated unsealed human erythrocyte membranes (IUM) were studied by fluorescence spectroscopy. Results indicated that both salicylates interact with human erythrocytes and their molecular models in a concentration-dependent manner perturbing their bilayer structures.     

Biological activity of new N-oxides of tertiary amines

Potential biological properties of newly synthesized single and double alkyl chain N-oxides of tertiary amines (NTA) were studied. Individual compounds in each of the series had alkyl chains of different length. Various experiments were performed to determine a mechanism of the interaction between NTA and model and biological membranes. These were measurements of hemolytic efficiencies of NTA (pig erythrocytes), their influence on the transition temperatures (DPPC liposomes), on potassium leakage from cucumber, its growth and chlorophyll content (Cucumis sativus cv. Krak F1), and on the resting membrane potential in alga cells (Nitellopsis obtusa). Also, prevention of erythrocyte membrane lipid oxidation induced by UV irradiation was studied. Potential antioxidative properties of NTA were additionally tested in radical chromogen (ABTS) experiments in which antioxidative efficiencies of NTA were compared to that of the standard antioxidant Trolox. It was found that NTA readily interacted with erythrocyte membranes. Their hemolyzing efficiency increased with the alkyl chain length. Slightly more intensive interaction was found for double alkyl chain compounds. Similar results were obtained in DSC experiments, where incorporation of NTA into liposomal membranes shifted the main transition temperatures and caused a broadening of the main transition peaks depending on the alkyl chain length. Double alkyl chain compounds were also found more efficiently influencing the growth of cucumber. Influence of NTA on the resting membrane potential of algae cells was not quite following the alkyl chain length rule found in erythrocyte and liposome experiments. Also potassium leakage and chlorophyll content determined in physiological experiments were not following the increase of lipophilicity of compounds. Most efficiently influencing those parameters were NTA having shorter alkyl chains, and efficiencies of single alkyl chain compounds were evidently stronger. Both methods used to test the antioxidative properties of NTA showed that they depended on the alkyl chain lengths of compounds within each series, but double alkyl chain ones exhibited markedly greater efficiency.     

Changes in the functional activity and kinetics of macrophages and lymphocytes as affected by retinoic acid

The influence of water-soluble compound of retinoic acid on the ability of human blood cell precursors to transform into macrophages, phagocytic macrophage activity, proliferation and marker properties of lymphocytes and the condition of erythrocytes was studied. It was found that retinoic acid caused erythrocyte damages, induced the ability of precursor cells to transforms into macrophages, did not increase significantly their functional activity and facilitated the formation of granulocyte-lymphocyte-macrophage aggregates. In the absence of macrophages, the action of retinoic acid was followed by the decrease in the expressivity of precursor cells to transform into macrophages, did by the suppression of their proliferative activity.     

Structure-activity relationships of some hederagenin diglycosides: haemolysis, cytotoxicity and apoptosis induction

Hederagenin saponins are largely represented in nature and possess many biological activities such as haemolytic, antiviral, fungicidal, molluscicidal or cytotoxic, partially due to their interaction with the cell membrane. The lysis of erythrocytes (haemolysis) is a simple test to evaluate this adsorption, and this activity has been linked to the structure of the aglycone and also depends on the sugar moiety of the saponin. To further complete our study of the structure-activity relationships of triterpenoid saponins, alpha-hederin and related hederagenin diglycosides were synthesized to better understand the influence of the second sugar (alpha-L-rhamnose, beta-D-xylose or beta-D-glucose) and the substitution of this sugar on alpha-L-arabinose (position 2, 3 or 4). Haemolysis and cytotoxic activity on KB cells were tested. These compounds probably interact with membrane cholesterol and produce destabilization of the membrane inducing haemolysis. Cytotoxicity could involve the same mechanism, although some saponins induce an apoptotic process. The nuclear structure of the KB cell was thus investigated by confocal microscopy. The cytotoxic activity of a second group of hederagenin glucoside saponins was also evaluated. Our results showed that cytotoxicity was a result of both the sugar part and the structure of genin (carboxylic acid or methyl ester).     

Structure–activity relationships of some hederagenin diglycosides: Haemolysis,cytotoxicity and apoptosis induction

Hederagenin saponins are largely represented in nature and possess many biological activities such as haemolytic, antiviral, fungicidal, molluscicidal or cytotoxic, partially due to their interaction with the cell membrane. The lysis of erythrocytes (haemolysis) is a simple test to evaluate this adsorption, and this activity has been linked to the structure of the aglycone and also depends on the sugar moiety of the saponin. To further complete our study of the structure–activity relationships of triterpenoid saponins, α-hederin and related hederagenin diglycosides were synthesized to better understand the influence of the second sugar (α-l-rhamnose, β-d-xylose or β-d-glucose) and the substitution of this sugar on α-l-arabinose (position 2, 3 or 4). Haemolysis and cytotoxic activity on KB cells were tested. These compounds probably interact with membrane cholesterol and produce destabilization of the membrane inducing haemolysis. Cytotoxicity could involve the same mechanism, although some saponins induce an apoptotic process. The nuclear structure of the KB cell was thus investigated by confocal microscopy. The cytotoxic activity of a second group of hederagenin glucoside saponins was also evaluated. Our results showed that cytotoxicity was a result of both the sugar part and the structure of genin (carboxylic acid or methyl ester).     

Influence of new hybrid antioxidants ichphans on erythrocyte morphology

Scanning electron microscopy was used to study the effects of the new generation of compounds ICHFANs, which have a combined antioxidant and acetylcholine esterase inhibitory effect on the surface architectonics of erythrocytes. The incorporation of each of the studied compounds with the positively charged quaternary ammonium in the erythrocyte membrane and their distribution in the itramembraneous space were accompanied by the formation of echinocytes, stomatocytes, and compensative effects on erythrocyte shape. The time-dependent morphological transformation of erythrocytes apparently is determined by changes in the distribution of the compounds between the outer and inner monolayers of the erythrocyte membrane. A difference in the morphological effects of compounds with different hydrophobic properties was revealed.     

Antioxidative activity of new N-oxides of tertiary amines: membrane model and chromogen studies

Potential antioxidative activities of three series of newly synthesized N-oxides were studied. Individual components in each of the series differed in the lipophilicities and number of free radical scavenging groups. Various methods were used to determine their antioxidative efficiencies: Prevention of erythrocyte membrane lipid oxidation induced by UV irradiation and chromogen experiments in which antioxidative efficiencies of compounds were compared to that of the standard antioxidant Trolox (a water-soluble vitamin E analogue). Additionally, some hemolytic (pig erythrocytes) and differential scanning calorimetry (DSC) measurements were performed to determine a mechanism of the interaction between membranes and N-oxides. It was found that N-oxides, especially those of long alkyl chains (> C12H25), readily interacted with both, erythrocyte and liposomal membranes. No marked differences were found in their protection of erythrocytes against oxidation. In most cases inhibition of oxidation changed between 15% and 25%. Still, it was far better than in chromogen experiments where suppression of free radicals reached 20% in the best case. It may be concluded that antioxidative capabilities of N-oxides are moderate. Studies on the interaction mechanism showed that incorporation of particular compounds into model membranes varied. Hemolysing activities of compounds increased with the elongation of the alkyl chain but differed for corresponding compounds of particular series indicating that lipophilicity of compounds is not the only factor determing their interaction with erythrocyte membranes. DSC experiments showed that N-oxides, upon incorporation into 1,2-dipalmitoyl-3-sn-phosphatidylcholine liposomes, shifted the subtransition (Tp) and the main transition (Tm). The shifts observed depended on the alkyl chain length. The effects differed for each series. It seems that in the case of long alkyl chain compounds the domain formation may take place. Generally, the decrease of Tm was greatest for the same compounds that exhibited the best hemolytic efficacy. The same conclusion concerns the decrease of cooperativity of the main transition and the observed changes suggest an increase in membrane fluidity. Both, erythrocyte and DSC experiments seem to indicate that compounds of particular series incorporate in a somewhat different way into membranes.     

Pig red blood cell hexokinase: Regulatory characteristics and possible physiological role

The regulatory properties of pig erythrocyte hexokinase III have been studied. Among mammalian erythrocyte hexokinases, the pig enzyme shows the highest affinity for glucose and a positive cooperative effect with n_H = 1.5 at all the MgATP concentrations studied (for 0.5 to 5 mm). Glucose at high concentrations is also an inhibitor of hexokinase III. Similarly, the apparent affinity constant for MgATP is independent of glucose concentration. Uncomplexed ATP and Mg are both competitive inhibitors with respect to MgATP. Glucose 6-phosphate, known as a stronger inhibitor of all mammalian erythrocyte hexokinases, is a poor inhibitor for the pig enzyme (K_i = 120 μm). Furthermore, this inhibition is not relieved by orthophosphate as with other mammalian red blood cell hexokinases. A variety of red blood cell-phosphorylated compounds were tested and found to be inhibitors of pig hexokinase III. Of these, glucose 1,6-diphosphate and 2,3-diphosphoglycerate displayed inhibition constants in the range of their intracellular concentrations. In an attempt to investigate the role of hexokinase type III in pig erythrocytes some metabolic properties of this cell have been studied. The adult pig erythrocyte is able to utilize 0.27 μmol of glucose/h/ml red blood cells (RBC) compared with values of 0.56–2.85 μmol/h/ml RBC for the other mammalian species. This reduced capacity to metabolize glucose results from a relatively poor ability of the cell membrane to transport glucose. In fact, all the glycolytic enzymes were present and a low intracellular glucose concentration was measured (0.5 mm against a plasma level of 5 mm). Furthermore, transport and utilization were concentration-dependent processes. Inosine, proposed as the major energy substrate of the pig erythrocyte, at physiological concentrations is not as efficient as glucose in maintaining reduced glutathione levels under oxidative stress. Furthermore, newborn pig erythrocytes (fully permeable to glucose) possess hexokinase type II as the predominant glucose-phosphorylating activity. This fact and the information derived from the study of the regulatory characteristics of hexokinase III and from metabolic studies on intact pig erythrocytes permit the hypothesis that the presence of this peculiar hexokinase isozyme (type III) enables the adult pig erythrocyte to metabolize low but appreciable amounts of glucose.     

Biophysical Mechanism of the Protective Effect of Blue Honeysuckle (Lonicera caerulea L. var. kamtschatica Sevast.) Polyphenols Extracts Against Lipid Peroxidation of Erythrocyte and Lipid Membranes

The aim of the present research was to determine the effect of blue honeysuckle fruit and leaf extracts components on the physical properties of erythrocyte and lipid membranes and assess their antioxidant properties. The HPLC analysis showed that the extracts are rich in polyphenol anthocyanins in fruits and flavonoids in leaves. The results indicate that both extracts have antioxidant activity and protect the red blood cell membrane against oxidation induced by UVC irradiation and AAPH. The extracts do not induce hemolysis and slightly increase osmotic resistance of erythrocytes. The research showed that extracts components are incorporated mainly in the external part of the erythrocyte membrane, inducing the formation of echinocytes. The values of generalized polarization and fluorescence anisotropy indicate that the extracts polyphenols alter the packing arrangement of the hydrophilic part of the erythrocyte and lipid membranes, without changing the fluidity of the hydrophobic part. The DSC results also show that the extract components do not change the main phase transition temperature of DPPC membrane. Studies of electric parameters of membranes modified by the extracts showed that they slightly stabilize lipid membranes and do not reduce their specific resistance or capacity. Examination of IR spectra indicates small changes in the degree of hydration in the hydrophilic region of liposomes under the action of the extracts. The location of polyphenolic compounds in the hydrophilic part of the membrane seems to constitute a protective shield of the cell against other substances, the reactive forms of oxygen in particular.     

Effects of cholesterol on physical properties of human erythrocyte membranes: impact on susceptibility to hydrolysis by secretory phospholipase A2

The ability of secretory phospholipase A₂ (sPLA₂) to hydrolyze cell membranes is highly dependent on the physical properties of the membrane. The effects of cholesterol on these properties have been characterized in artificial bilayers and found to alter sPLA₂ activity significantly. It is hypothesized that the natural difference in cholesterol content between erythrocytes and leukocytes is in part responsible for their differing susceptibility to hydrolysis by sPLA₂. To test this hypothesis, defined amounts of cholesterol were removed from erythrocyte membranes using methyl-β-cyclodextrin. Treatment of cells with methyl-β-cyclodextrin increased the hydrolysis rate and total substrate hydrolyzed by sPLA₂. In general, this effect of cholesterol removal was more pronounced at higher temperatures. Comparison of the level of membrane order (assessed with the fluorescent probe laurdan) with hydrolysis rate revealed that sPLA₂ activity was greatly enhanced upon significant reductions in lipid order. Additional treatment of the cells with calcium ionophore further enhanced the hydrolysis rate and altered the relationship with membrane order. These data demonstrated that interactions with sPLA₂ observed in artificial bilayers apply to biological membranes. It is also proposed that the high level of cholesterol in erythrocyte membranes is a protective mechanism to guard against hydrolytic enzymes.     

The Effects of Atorvastatin Therapy on Rheological Characteristics of Erythrocyte Membrane, Serum Lipid Profile and Oxidative Status in Patients with Dyslipidemia

The statins, most commonly used in the treatment of hyperlipidemia, have certain beneficial effects including improved endothelial function, plaque stability and decreased oxidative stress and inflammation, beyond their lipid-lowering effect in plasma. We evaluated the pleiotropic impact of atorvastatin on erythrocyte structural/mechanical properties and lipid peroxidation in dyslipidemics. The study group included 44 patients with dyslipidemia and was divided into subgroups according to triglyceride and cholesterol levels as hypercholesterolemic (n?=?29) and mixed-type hyperlipidemic (n?=?15). Subjects were given 10?mg atorvastatin per day for 12?weeks. Changes in serum lipid composition, lipid contents, Na⁺/K⁺-ATPase activity and osmotic fragility in erythrocytes and oxidative stress parameters of erythrocytes and plasma were studied. Atorvastatin therapy improved the serum lipid profile of both subgroups. This alteration was accompanied by a decreased level of cholesterol in erythrocyte membranes. Moreover, enhanced activity of Na⁺/K⁺-ATPase in erythrocytes reflected the improvements in membrane lipids of both subgroups. However, a significant change was observed in osmotic fragility values of the mixed-typed dyslipidemic group. This treatment lowered the lipid peroxidation in plasma and erythrocytes and increased plasma total antioxidant capacity in all groups. The present study shows that the use of atorvastatin reversed the structural and functional features of erythrocyte membranes in dyslipidemic subjects. Also, hypolipidemic therapy had a beneficial impact on a balance between oxidant and antioxidant systems.     

Influence of band 3 protein absence and skeletal structures on amphiphile- and Ca(2+)-induced shape alterations in erythrocytes: a study with lamprey (Lampetra fluviatilis), trout (Onchorhynchus mykiss) and human erythrocytes

Amphiphiles which induce either spiculated (echinocytic) or invaginated (stomatocytic) shapes in human erythrocytes, and ionophore A23187 plus Ca(2+), were studied for their capacity to induce shape alterations, vesiculation and hemolysis in the morphologically and structurally different lamprey and trout erythrocytes. Both qualitative and quantitative differences were found. Amphiphiles induced no gross morphological changes in the non-axisymmetric stomatocyte-like lamprey erythrocyte or in the flat ellipsoidal trout erythrocyte, besides a rounding up at higher amphiphile concentrations. No shapes with large broad spicula were seen. Nevertheless, some of the 'echinocytogenic' amphiphiles induced plasma membrane protrusions in lamprey and trout erythrocytes, from where exovesicles were shed. In trout erythrocytes, occurrence of corrugations at the cell rim preceded protrusion formation. Other 'echinocytogenic' amphiphiles induced invaginations in lamprey erythrocytes. The 'stomatocytogenic' amphiphiles induced invaginations in both lamprey and trout erythrocytes. Surprisingly, in trout erythrocytes, some protrusions also occurred. Some of the amphiphiles hemolyzed lamprey, trout and human erythrocytes at a significantly different concentration/membrane area. Ionophore A23187 plus Ca(2+) induced membrane protrusions and sphering in human and trout erythrocytes; however, the lamprey erythrocyte remained unperturbed. The shape alterations in lamprey erythrocytes, we suggest, are characterized by weak membrane skeleton-lipid bilayer interactions, due to band 3 protein and ankyrin deficiency. In trout erythrocyte, the marginal band of microtubules appears to strongly influence cell shape. Furthermore, the presence of intermediate filaments and nuclei, additionally affecting the cell membrane shear elasticity, apparently influences cell shape changes in lamprey and trout erythrocytes. The different types of shape alterations induced by certain amphiphiles in the cell types indicates that their plasma membrane phospholipid composition differs.     

The effect of synthetic antioxidants,anphen derivatives,on erythrocyte morphology

The effect of new synthetic antioxidants, anphens, on erythrocyte morphology was studied. Insignificant cell transformations induced by the hydrophilic derivative of anphen-1 into echinocytes, as well as cell transformations into stomatocytes under the action of hydrophobic derivatives of anphens-2, 3, and 4 were revealed. The data we obtained indicate the intercalation of these compounds into the erythrocyte membrane. The distribution of compounds in the intra-membrane space depends on their hydrophobicity. A hydrophilic compound, anphen-1, is predominantly located in the outer monolayer of the membrane, while hydrophobic derivatives occur in the inner monolayer. It is proposed that the biological activities of anphen-3 and anphen-4 can occur in both monolayers as they move through the membrane, while the hydrophilic compound, anphen-1, exerts an insignificant membranotropic effect and can act only in the outer monolayer of the membrane. Variability in the efficiency of the concentration-dependent modifying action of the compounds with different hydrophobic properties has been found.