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PubMedDate not supplied

Effects of certain micronutrients and melatonin on plasma lipid, lipid peroxidation, and homocysteine levels in rats.

BACKGROUND: Numerous studies suggest an association between high intake of antioxidant vitamins and fish oil and reduced risk of coronary heart disease. Hyperhomocysteinemia has also been identified as an independent risk factor for arteriosclerosis. In this paper, we aimed to evaluate the effects of vitamin E, vitamin C, vitamin C 6 palmitate (VC6P), lipoic acid, fish oil, and melatonin supplementation on lipid peroxidation, plasma lipid, and homocysteine (Hcy) levels in rats. METHODS: Animals were divided into seven groups: one was used as control and each remaining group was supplemented with one substance for 6 weeks. All substances were dissolved in olive oil and injected intraperitoneally (i.p.) with the exception of vitamin C, which was dissolved in drinking water. Plasma Hcy, lipid peroxidation, and lipids were determined. RESULTS: Plasma malondialdehyde (MDA) levels decreased significantly in melatonin (p <0.01), lipoic acid (p <0.01), and vitamin E (p <0.05) groups. On the other hand, supplementation with vitamin C and VC6OP lowered MDA levels moderately but not significantly (p >0.05). Fish oil supplementation caused a slight but insignificant increase in plasma MDA levels (p >0.05). Plasma lipid levels in animals treated with melatonin, vitamin E, vitamin C, lipoic acid, and fish oil were significantly lower than those of controls; however, treatment of rats with VC6P has no significant effect on plasma lipid level. Melatonin and fish oil administration significantly lowered plasma Hcy levels, whereas VC6P elevated its level. There was no significant effect of vitamin E, vitamin C, and lipoic acid on levels of plasma Hcy. CONCLUSIONS: Our data suggest that supplementation with antioxidants appears to be hypolipidemic. In addition to these beneficial effects, administration of melatonin and fish oil deserves careful consideration as a measure to lower plasma Hcy levels and reduce risk of cardiovascular diseases.

Animals↗
PubMed1997

Role of phosphatidylethanolamine lipids in the stabilization of protein-lipid contacts.

We have investigated the effect of lipids with phosphatidylethanolamine (PE) head groups on the stabilization of contacts between the tryptophan side chains of gramicidin and the lipid head groups. We initially developed two fluorescence methods that can be correlated to the spontaneous curvature of DOPC/DOPE and DOPC/DOPEme. One is based on bilayer structure and measures the rotational motion of a probe located close to the membrane surface relative to a more deeply-buried probe. The second is based on surface hydration/polarity and measures the emission energy of a polarity-sensitive probe located on the membrane surface. We used these methods to estimate the pseudo-curvature (i.e., curvature obtained by fluorescence measurements) of lipids with dimyristyl chains, and their pressure and temperature dependence. We then investigated the stability of gramicidin tryptophan-lipid contacts in DMPC/DMPE as a function of temperature and pressure. Stability was assessed by tryptophan rotational motion as determined by fluorescence anisotropy, since rotational motion is limited when the indoles are hydrogen bonded to the lipid head groups. The results suggest that the presence of PE lipids destabilizes these contacts due to either their smaller size relative to PC head groups, or their tendency to self-interact. Fluorescence quenching studies support these results.

Chemical Phenomena↗
PubMed2000

Spin trapping of lipid radicals with DEPMPO-derived spin traps: detection of superoxide, alkyl and alkoxyl radicals in aqueous and lipid phase.

The spin trap 5-(diethoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DEPMPO) forms a superoxide adduct with a half-life of almost 15 min. DEPMPO is very hydrophilic and its use for the detection of radicals in the lipid phase (lipid-derived radicals and superoxide generated in the lipid phase) is therefore limited due to its very low concentration in the lipid phase. For the detection of lipid-derived radicals, three derivatives of DEPMPO with increasing degree of lipid solubility have been investigated: 5-(di-n-propoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DPPMPO), 5-(di-n-butoxyphosphoryl)-5-methyl-1-pyrroline N-oxide (DBPMPO), and 5-(bis-(2-ethylhexyloxy)phosphoryl)-5-methyl-1-pyrroline N-oxide (DEHPMPO). As compared with the spin trap DMPO, the half-lives of the respective superoxide adducts were clearly higher in aqueous solutions of the spin traps, which facilitates qualitative ESR measurements. The stability of the superoxide spin adducts formed with the various lipophilic spin traps in aqueous buffer were similar to those observed with DEPMPO (half-life: 7-11 min.). In model experiments using Fe(3+)-catalyzed nucleophilic addition of methanol or tert-butanol to the respective spin trap the respective alkoxyl radical adducts were formed in aqueous solution as transient species in the presence of high concentrations of the alcohol. Upon dilution with water the alkoxyl group was substituted by water, giving the respective hydroxyl adduct of the spin trap. Care must therefore be taken when Fenton-type reactions are used for the generation of radicals such as the use of Fe(2+) complexes with phosphate or DTPA or inactivation of iron by addition of "Desferal" (Novarti's Pharma GmbH, Vienna, Austria) after a short incubation time. Addition of Fe(2+) under anaerobic conditions to an aqueous suspension of linoleic acid hydroperoxide and the spin trap resulted in the detection of three different species: a carbon-centered radical adduct, an acyl radical adduct, and the hydroxyl adduct. In the presence of oxygen a different species was observed with DEPMPO, DPPMPO, and DBPMPO, which was only slightly suppressed upon the addition of SOD, possibly the respective spin adduct of either the alkylperoxyl radical or, in analogy to DMPO, a secondary alkoxyl radical.

Cyclic N-Oxides↗
PubMed2000

Self-regulation of the lipid content of membranes by non-bilayer lipids: a hypothesis.

Many biological membranes contain lipids that do not form a lamellar phase but the roles of these lipids are not well understood. An artificial membrane assembled from the main non-bilayer lipid and the major integral protein of pea thylakoids revealed that the protein spatially inhibits the formation of non-bilayer structures in the lamellae. Without this inhibition, excess lipids are secreted, creating lipid reservoirs for metabolism and/or later uptake. This determines the protein:lipid ratio in the membrane and hence the balance between structural flexibility and the stability of the key constituents that participate in cooperative interactions.

Lipid Bilayers↗
PubMed1994

Annexin IV reduces the rate of lateral lipid diffusion and changes the fluid phase structure of the lipid bilayer when it binds to negatively charged membranes in the presence of calcium.

Bovine annexin IV (endonexin) was bound to supported planar bilayers composed of 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) in the first monolayer facing the substrate, and varying mole fractions of POPC, 1-palmitoyl-2-oleoylphosphatidylglycerol (POPG) and small amounts of the fluorescent lipid analogs NBD-PC or NBD-PG in the second monolayer facing the large aqueous compartment. Lateral diffusion coefficients and mobile fractions of these phospholipids were measured by fluorescence recovery after photobleaching (FRAP) as a function of protein concentration and lipid composition in the presence of 2 mM CaCl2 or 1 mM EDTA. In the absence of annexin IV, the lateral diffusion coefficients depended only little on the POPC:POPG ratios and were approximately 3.0 microns2/s for NBD-PG (no Ca2+), 2.5 microns2/s for NBD-PG (2 mM Ca2+), and 1.6 microns2/s for NBD-PC (with or without 2 mM Ca2+). In the presence of 2 mM Ca2+ these diffusion coefficients decreased as a function of the added annexin concentration. A transition from a state with "rapid" lipid diffusion to a state with "slow" lipid diffusion occurred at about 80 nM annexin IV and was independent of the POPC:POPG ratio. In addition to reducing the lipid lateral diffusion coefficients, annexin IV also gave rise to two-component lateral diffusion of the lipids in these mixed bilayers. The split of the single diffusion coefficient of NBD-PG into two components occurred at most POPC:POPG ratios upon binding of annexin IV, but required higher annexin concentrations at mole fractions of POPC between 66 and 82 mol % than at high mole fractions of POPG or 90 mol % POPC.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1986

Phase equilibria of membrane lipids from Acholeplasma laidlawii: importance of a single lipid forming nonlamellar phases.

A basis for the reorganization of the bilayer structure in biological membranes is the different aggregate structures formed by lipids in water. The phase equilibria of all individual lipids and several in vivo polar lipid mixtures from acyl chain modified membranes of Acholeplasma laidlawii were investigated with different NMR techniques. All dioleoyl (DO) polar lipids, except monoglucosyldiglyceride (MGDG), form lamellar liquid crystalline (L alpha) phases only. The phase diagram of DOMGDG reveals reversed cubic (III), reversed hexagonal (HII), and L alpha phases. In mixtures of DOMGDG and dioleoyldiglycosyldiglyceride (DODGDG), the formation of an III (or HII) phase is enhanced by DOMGDG and low hydration or high temperatures. For in vivo mixtures of all polar DO lipids, a transition from an L alpha to an III phase is promoted by low hydration or high temperatures (50 degrees C). The phospholipids are incorporated in this III phase. Likewise, III and HII phases are formed at similar temperatures in a series of in vivo mixtures with different extents of acyl chain unsaturation. However, their melting temperatures (Tm) vary in an expected manner. All cubic and hexagonal phases, except the III phase with DOMGDG, exist in equilibrium with excess water. The maximum hydration of MGDG and DGDG is similar and increases with acyl chain unsaturation but is substantially lower than that for, e.g., phosphatidylcholine. The translational diffusion of the lipids in the cubic phases is rapid, implying bicontinuous structures. However, their appearances in freeze-fracture electron microscope pictures are different. The III phase of DOMGDG belongs to the Ia3d space group.(ABSTRACT TRUNCATED AT 250 WORDS)

Acholeplasma laidlawii↗
PubMed1986

Metabolic changes of membrane lipid composition in Acholeplasma laidlawii by hydrocarbons, alcohols, and detergents: arguments for effects on lipid packing.

The packing of lipids into different aggregates, such as spheres, rods, or bilayers, is dependent on the hydrophobic volume, the hydrocarbon-water interfacial area, and the hydrocarbon chain length of the participating molecules, according to the self-assembly theory [Israelachvili, J. N., Marcelja, S., & Horn, R. G. (1980) Q. Rev. Biophys. 13, 121-200]. The origin of the participating molecules should be of no importance with respect to their abilities to affect the above-mentioned parameters. In this investigation, Acholeplasma laidlawii, with a defined acyl chain composition of the membrane lipids, has been grown in the presence of three different classes of foreign molecules, known to partition into model and biological membranes. This results in an extensive metabolic alteration in the lipid polar head group composition, which is expressed as changes in the molar ratio between the lipids monoglucosyldiglyceride (MGDG) and diglucosyldiglyceride (DGDG), forming reversed hexagonal and lamellar phases in excess water, respectively. The formation of nonlamellar phases by A. laidlawii lipids depends critically upon the MGDG concentration [Lindblom, G., Brentel, I., Sjölund, M., Wikander, G., & Wieslander, A. (1986) Biochemistry (preceding paper in this issue)]. The foreign molecules tested belong to the following groups: nonpolar organic solvents, alcohols, and detergents. Their effects on the gel to liquid crystalline phase transition temperature (Tm), on the order parameter of the acyl chains, and on the phase equilibria between lamellar and nonlamellar liquid crystalline phases in lipid-water model systems are known in several instances.(ABSTRACT TRUNCATED AT 250 WORDS)

Acholeplasma laidlawii↗
PubMed2001

Partitioning of lipidated peptide sequences into liquid-ordered lipid domains in model and biological membranes.

We have used a fluorescence assay and detergent fractionation to examine the partitioning of different fluorescent lipidated peptides, with sequences and lipid substituents matching those found in various classes of lipidated cellular proteins, into liquid-ordered (raft-like) domains in lipid bilayers. Peptides incorporating isoprenyl groups, or multiple unsaturated acyl chains, show negligible affinity for liquid-ordered domains in mixed-phase liquid-ordered/liquid-disordered (l(o)/l(d)) bilayers composed of dipalmitoylphosphatidylcholine, a spin-labeled unsaturated phosphatidylcholine, and cholesterol. By contrast, peptides incorporating multiple S- and/or N-acyl chains, or a cholesterol residue plus an N-terminal palmitoyl chain, show significant partitioning into liquid-ordered domains under the same conditions. Interestingly, the affinity of a lipidated peptide for l(o) domains can be strongly influenced, not only by the structures of the lipid substituents but also by the nature and the positions of their attachment to the peptide chain. These results are well correlated with those obtained from parallel assays based on low-temperature detergent fractionation. Using the latter approach, we further demonstrate that a truly minimal l(o) domain partitioning motif [myristoylGlyCys(palmitoyl)-] can mediate efficient incorporation into the "raft" fraction of COS-7 cell membranes.

1,2-Dipalmitoylphosphatidylcholine↗
PubMed1997

Determination of singlet oxygen-specific versus radical-mediated lipid peroxidation in photosensitized oxidation of lipid bilayers: effect of beta-carotene and alpha-tocopherol.

Photosensitized oxidation reactions damage tissue by catalyzing the formation of oxyradicals and singlet oxygen. beta-Carotene is hypothesized to exert photoprotective effects by quenching singlet oxygen formed by Type II reactions and by scavenging free radicals formed by Type I reactions. beta-Carotene antioxidant mechanisms were studied in a phospholipid membrane model of photooxidation with a new isotope dilution gas chromatography-mass spectrometry (GC-MS) assay that quantitatively distinguishes singlet oxygen-mediated and radical-mediated lipid peroxidation. This assay measures 9- and 10-hydroxylinoleate methyl esters and was used to generate photooxidation profiles for the photosensitizers methylene blue, Rose Bengal, and tetraphenylporphine. These profiles indicate a shift from Type II to Type I photooxidation mechanisms in later stages of photooxidation. beta-Carotene (0.45 mol %) inhibited singlet oxygen-mediated lipid peroxidation at early stages of methylene blue-sensitized photooxidation. Production of radical-mediated products increased faster than singlet oxygen-mediated products at later stages. beta-Carotene-5,8-endoperoxide, a specific marker for singlet oxygen oxidation of beta-carotene in solution, was unstable under the incubation conditions and was not detected in this system. alpha-Tocopherol (0.45 mol %) was ineffective in inhibiting photosensitized lipid peroxidation, whereas 4.5 mol % alpha-tocopherol inhibited almost all radical-mediated lipid peroxidation as well as early-stage singlet oxygen-mediated lipid peroxidation. Cumene hydroperoxide stimulated radical-mediated lipid peroxidation, indicating that accumulation of hydroperoxides from Type II photooxidation may enhance Type I reactions. These data suggest that singlet oxygen quenching, rather than radical scavenging reactions, accounts for the photoprotective actions of beta-carotene.

Chromatography, High Pressure Liquid↗
PubMed1995

The chemistry of lipid alkoxyl radicals and their role in metal-amplified lipid peroxidation.

Reaction of polyunsaturated fatty acid hydroperoxides with metal complexes generates lipid alkoxyl radicals and metal-oxo complexes. Lipid alkoxyl radicals are presumed to be the species responsible for metal-amplified lipid peroxidation because of the chemical analogy of simple organic alkoxyl radicals to the hydroxyl radical. However, polyunsaturated fatty acid alkoxyl radicals exhibit a rich and diverse chemistry that is dominated by intramolecular cyclization to epoxyallylic radicals. Studies described herein demonstrate that the equilibrium between cyclization and ring-opening of epoxyallylic radicals lies overwhelmingly toward cyclization. Thus lipid alkoxyl radicals have a steady-state concentration that is so low that their contribution to metal-amplified lipid peroxidation is insignificant. In fact, the species responsible for metal amplification of lipid peroxidation appears to be the epoxyperoxyl radical formed by coupling the epoxyallylic radical to molecular oxygen.

Free Radicals↗
PubMed2003

Lipid droplet and milk lipid globule membrane associated placental protein 17b (PP17b) is involved in apoptotic and differentiation processes of human epithelial cervical carcinoma cells.

The intracellular role of placental protein 17b (PP17b)/TIP47 has been controversial, because it is considered to be a protein required for mannose 6-phosphate receptor transport from endosome to trans-Golgi as well as a neutral lipid droplet-associated protein. The similarity between the amino acid sequences of PP17 variants, adipophilin and perilipins, and between their gene structures indicate that PP17b as well as other alternatively spliced PP17 variants belong to the lipid storage droplet protein family, containing also some differentiation factors. Using a specific antibody, PP17b was detected in lipid droplet fractions and co-localized with neutral lipid droplets stained by Nile red, and fluorescently labelled PP17 antibody in HeLa cells with confocal microscopy. PP17b was also detected in milk, associated to milk lipid globule membranes. Cytostatic agents induced apoptosis and PP17b synthesis in HeLa cells, which was significantly inhibited by protein kinase C (PKC) inhibitor, indicating the involvement of NF-kappa B and AP-1 transcription factors in this process, while protein kinase A (PKA) inhibitor had only a modest inhibitory effect. Cell differentiation induced by dibutyryl cyclic AMP or phorbol myristate acetate also increased PP17b synthesis, demonstrating its strong involvement in cell differentiation. PP17b synthesis was higher in M than in G0/G1 phases in control, apoptotic and differentiated cells. This data shows that PP17b is a neutral lipid droplet-associated protein, and its expression is regulated by PKC- and PKA-dependent pathways.

Amino Acid Sequence↗
PubMed2002

Structure of apolipophorin-III in discoidal lipoproteins. Interhelical distances in the lipid-bound state and conformational change upon binding to lipid.

The structure of apolipophorin III in the lipid-bound state and the extent of the conformational change that takes place when the five-helix bundle apolipoprotein binds to a lipoprotein lipid surface were investigated by fluorescence resonance energy transfer in discoidal lipoproteins. Four intramolecular interhelical distances between helix pairs 1-4, 2-4, 3-4, and 5-4 were estimated by fluorescence resonance energy transfer in both the lipid-free and the lipid-bound states. Depending on the helices pairs, the intramolecular interhelical distances increased between 15 and > or = 20 A upon binding of the apolipoprotein to lipid, demonstrating for the first time that binding to lipid is accompanied by a major change in interhelical distances. Using discoidal lipoproteins made with a combination of apolipophorin III molecules containing donor and acceptor groups and apolipophorin III molecules containing neither donor nor acceptor groups, it was possible to obtain information about intermolecular interhelical distances between the helix 4 of one apolipoprotein and the helices 1, 2, 3, and 5 of a second apolipoprotein residing in the same discoidal lipoprotein. Altogether, the estimated intermolecular and intramolecular interhelical distances suggest a model in which the apolipoprotein arranges in pairs of antiparallel and fully extended polypeptide chains surrounding the periphery of the bilayer disc.

Apolipoproteins↗
PubMed1987

Radiation-induced lipid peroxidation: influence of oxygen concentration and membrane lipid composition.

Radiation-induced lipid peroxidation in phospholipid liposomes was investigated in terms of its dependence on lipid composition and oxygen concentration. Non-peroxidizable lipid incorporated in the liposomes reduced the rate of peroxidation of the peroxidizable phospholipid acyl chains, possibly by restricting the length of chain reactions. The latter effect is believed to be caused by interference of the non-peroxidizable lipids in the bilayer. At low oxygen concentration lipid peroxidation was reduced. The cause of this limited peroxidation may be a reduced number of radical initiation reactions possibly involving oxygen-derived superoxide radicals. Killing of proliferating mammalian cells, irradiated at oxygen concentrations ranging from 0 to 100 per cent, appeared to be independent of the concentration of peroxidizable phospholipids in the cell membranes. This indicates that lipid peroxidation is not the determining process in radiation-induced reproductive cell death.

Animals↗
PubMed1978

Effects of force-feeding and dietary cellulose on liver lipid accumulation and lipid composition of liver and plasma in growing chicks.

Changes of content and composition of lipid in liver and plasma affected by force-feeding and dietary cellulose were investigated in 14-day old Single-Comb White Leghorn male chicks. They were given a purified high energy diet (starch-casein diet without fiber) supplemented with or without dietary cellulose. Chicks were fed ad libitum or force-fed the experimental diet. Force-feeding of excess food improved the growth rate of chicks and feed efficiency, but feeding of cellulose did not affect body weight gain and feed efficiency, though a slight improvement in nitrogen retention was observed. Liver weight and lipid content in liver and plasma were markedly elevated by force-feeding, and were markedly depressed by dietary cellulose in the force-fed chicks. It is suggested that changes of liver lipid by force-feeding and dietary cellulose are mainly originated from the changes of triglyceride in the liver lipid. No marked changes were observed in fatty acid composition of abdominal fat and liver lipid in the cellulose-fed chicks. These results suggest that dietary cellulose may affect lipid metabolism in growing chicks.

Animals↗
PubMed1996

Plasma lipids, erythrocyte membrane lipids and blood pressure of hypertensive women after ingestion of dietary oleic acid from two different sources.

OBJECTIVE: To study the effect of a diet rich in mono-unsaturated fatty acids (MUFA), from high-oleic sunflower oil (HOSO) and olive oil, on plasma lipids, erythrocyte membrane lipids (including fatty acid composition) and blood pressure of hypertensive (normocholesterolaemic or hypercholesterolaemic) women. METHODS: There were 16 participants who were hypertensive women aged 56.2 +/- 5.4 years. The participants ate a diet enriched with HOSO or olive oil for two 4-week periods with a 4-week washout period before starting the second type of MUFA diet. At entry and during study of each diet, plasma lipids and apolipoproteins were measured by conventional enzymatic methods. Erythrocyte membrane lipid and fatty acid compositions were analysed by means of the latroscan thin-layer chromatography/flame ionization detection technique and by gas chromatography, respectively. Blood pressure was also measured. The statistical analysis was conducted by using Student's two-tailed paired t-test. RESULTS: In both groups of hypertensive patients, there was a significant increase in plasma high-density lipoprotein (HDL) cholesterol concentration after the HOSO or olive oil diets, with regard to baseline. Additionally, a significant decrease in plasma HDL2 cholesterol concentration and an increase in plasma HDL3 cholesterol concentration were evident. The membrane free-cholesterol concentration increased significantly and the phospholipid concentration decreased significantly in erythrocytes after the olive oil diet, though both MUFA diets produced a significant decrease in the concentration of membrane esterified cholesterol. Therefore, the molar ratio of cholesterol to phospholipids was raised significantly in the erythrocyte membrane of hypertensive women after the dietary olive oil, but not after the HOSO diet. In the hypertensive and normo-cholesterolaemic group the HOSO diet significantly increased the content in the erythrocyte membrane of oleic, eicosenoic, arachidonic and docosapentaenoic acids, whereas the olive oil diet increased the content of palmitoleic acid and long-chain polyunsaturated fatty acids of the n-3 family besides, compared with baseline. A significant decrease in linoleic acid was also evident. In the hypertensive and hypercholesterolaemic group, the HOSO diet resulted in significant increases in palmitoleic, oleic, eicosenoic and behenic acids, whereas the olive oil diet enhanced the content of arachidonic, docosapentaenoic and docosahexaenoic acids besides, with respect to baseline. In addition, there was a significant decrease in stearic acid, but only after dietary olive oil was there a decrease in linoleic acid. The most important differences between the two MUFA diets were the increase in n-3 fatty acids and the decrease in the n-6; n-3 fatty acids ratio after dietary olive oil in the erythrocyte membranes of hypertensive patients. Interestingly, a significant reduction in systolic and diastolic blood pressures was only evident after the ingestion of olive oil. CONCLUSION: These data suggest that the beneficial effects of dietary olive oil on the plasma lipids and lipoprotein profile, lipid and fatty acid composition of erythrocyte membrane, and blood pressure in women with untreated essential hypertension are not found equally for the HOSO-rich diet, despite both vegetable oils providing a similar concentration of MUFA.

Aged↗
PubMed1993

The interaction of daunomycin with model membranes. Effect of the lipid physical state and the lipid composition.

The sensitivity of the keto and carbonyl infrared bands of daunomycin (DNM) to hydrogen bonding with the solvent, has been used to study the effect of the physical state and lipid composition of the bilayer on drug location. Our results show that penetration of daunomycin into dihexadecylphosphatidylcholine (Hxd2GroPCho) or dipalmitoylphosphatidylcholine bilayers, is dependent on the molecular packing of the lipid. DNM incorporates into the bilayer once the interdigitation of the gel phase of Hxd2GroPCho has been removed, above the pretransition temperature. Melting of the hydrocarbon chains of both lipids, at the main transition temperature, allows a similar and deeper drug penetration into the bilayers. Experiments using liposomes with different lipid compositions suggest that the relative concentration of certain lipids may modulate the location of DNM within the bilayer. Cholesterol, in a concentration-dependent manner, inhibits incorporation of anthracycline into apolar regions of the bilayer, while the presence of the negatively charged lipid dihexadecylphosphatidic acid is able to prevent the inhibitory effect of the steroid, allowing deeper penetration of the drug. Due to the importance of drug-membrane interactions in anthracycline cytotoxicity, the relevance of the observed differences in daunomycin location, caused by physical and/or chemical changes in the biological membranes, is discussed.

Cholesterol↗
PubMed1987

Malathion induced alterations in the lipid profile and the rate of lipid peroxidation in rat brain and spinal cord.

Malathion, known as a low toxic pesticide, is frequently used in the third world. Neurotoxic manifestations of malathion were evaluated on various lipids and lipid peroxidation in different brain areas following intraperitoneal injections (150 mg/kg body weight for 7 consecutive days) to albino rats. Clinical investigations show that malathion produced hypomotor activity and hyperthermia. Lipid components were differently affected by this pesticide, where total lipids and phospholipids were diminished in the spinal cord and brain stem, respectively. Increased contents of cholesterol were found in the cerebellum and spinal cord. Also, total lipids were increased in the cerebellum. The cholesterol/phospholipids ratio was increased in the cerebellum, brain stem and spinal cord. Rate of lipid peroxidation was found to be increased in all parts of the brain following malathion intoxication.

Animals↗
PubMed1989

Macrophage activation by an ornithine-containing lipid or a serine-containing lipid.

alpha-N-(3-Acyloxyacyl)-ornithine (or -serine) is the structure of lipoamino acids obtained by us previously from some gram-negative bacteria (Y. Kawai and I. Yano, Eur. J. Biochem. 136:531-538, 1983; Y. Kawai, I. Yano, and K. Kaneda, Eur. J. Biochem. 171:73-80, 1988; Y. Kawai, I. Yano, K. Kaneda, and E. Yabuuchi, Eur. J. Biochem. 175:633-641, 1988). The 3-acyloxyacylamide structure is present in both the lipoamino acids and lipid A of lipopolysaccharide (endotoxin). The efficacy of lipoamino acids (an ornithine-containing lipid and a serine-containing lipid) in activating C3H/HeSlc mouse peritoneal exudate macrophages was compared with that of bacterial lipopolysaccharide, because the two types of substances were expected to exhibit similar biological activities and physiological functions on the basis of their structural similarities. Actually, the lipoamino acids, as well as lipopolysaccharide, strongly activated the macrophages to generate the immunoregulatory substances prostaglandin E2 and interleukin-1, but their effect on the induction of L929 cell cytolytic factor (a possible tumor necrosis factor), another immunoregulatory substance, was weaker than that of lipopolysaccharide. The effect of lipoamino acids on the cytotoxicity of macrophages for EL-4 leukemia cells was very weak. However, all of these activities, as far as tested, were strongly enhanced by synergistic action with gamma interferon. Only the serine-containing lipid killed both C3H/HeSlc and C3H/HeJ macrophages to almost the same degree as endotoxin killed C3H/HeSlc macrophages. On the other hand, lethal toxicity for mice was not found with either the ornithine-containing lipid or the serine-containing lipid, even when 7 mg of compound was injected into a mouse. These studies suggest that the lipoamino acids are nontoxic characteristic immunoactivators.

Animals↗