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E Niki

Publications and source records attributed to E Niki.

At least 55 records · Page 3Linked to original sources
PubMed1998

Stoichiometric and kinetic studies on Ginkgo biloba extract and related antioxidants.

Owing to increasing evidence showing the importance of lipid peroxidation in oxidative stress in vivo, the role and evaluation of antioxidants have received much attention. Ginkgo biloba extract (GBE), well-known as an efficient drug against diseases induced by free radicals, has been suggested to exert its effect by antioxidant action. A method was established to determine the activity of GBE as a hydrogen donor by stoichiometric and kinetic studies, and GBE was compared with several other antioxidants such as alpha-tocopherol, propyl gallate, and two kinds of flavonoids which are found in GBE, quercetin, and kaempferol. It was found that there were 6.62 x 10(19) active hydrogens in 1 g of GBE. Stoichiometric studies showed that one molecule of alpha-tocopherol reacted with one molecule of galvinoxyl radical. For quercetin, kaempferol and propyl gallate, the experimental stoichiometric numbers were 4.0, 1.9, and 3.1, respectively. The rates of reaction of antioxidants with galvinoxyl in ethanol were determined spectrophotometrically, using a stopped-flow technique. The second-order rate constant, k2, obtained at 25 degrees C was 0.13 (g/L)(-1)s(-1) for GBE and 5.9 x 10(3), 2.1 x 10(3), 1.2 x 10(4), and 2.4 x 10(3) M(-1)s(-1) for quercetin, kaempferol, propyl gallate, and alpha-tocopherol, respectively. The second-order rate constant, k2', on the molar basis of active hydroxyl groups in the tested substances obtained at 25 degrees C decreased in the order of propyl gallate > alpha-tocopherol > quercetin > GBE approximately kaempferol. This is the first study on GBE as an antioxidant which reports both stoichiometric and kinetic results.

Antioxidants↗
PubMed1998

Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous micelles. II. Effect of antioxidants.

We have reported that the peroxyl radicals derived from methyl eicosapentaenoate (20:5n-3) are more polar than those from methyl linoleate (18:2n-6) since the former peroxyl radicals have at least two molecules of oxygen in a molecule while the latter peroxyl radical has one. This lowers the oxidizability for 20:5n-3 in aqueous Triton X-100 micelles by enhancing the termination reaction rate for peroxyl radicals and by reducing the rate of propagation since there may be more polar peroxyl radicals derived from 20:5n-3 at the surface than within the micelle core. In this study, we measured the effect of three antioxidants, di-tert-butyl-4-methylphenol (BHT), 2,2,5,7,8-pentamethyl-6-chromanol (PMC) and 2-carboxy-2,5,7,8-tetramethyl-6-chromanol (Trolox), on the oxidation of lipids in aqueous micelle. Antioxidants give a clear induction period during oxidation of 18:2n-6 initiated with a water-soluble radical initiator, and its induction length decreases in the order of BHT > PMC > Trolox. This is consistent with the proposed location of three antioxidants: being in the core of micelle, at the surface, or in aqueous phase, respectively. However, BHT does not inhibit the oxidation of 20:5n-3 efficiently, and its rate of oxidation is slower than that observed in the oxidation of 18:2n-6, supporting the idea that polar peroxyl radicals derived from 20:5n-3 are preferentially located at the surface of the micelle. Similar results were obtained when oxidation was initiated with a lipid-soluble radical initiator except antioxidants had lesser effect on the oxidation rate of 20:5n-3.

Aerobiosis↗
PubMed1998

Oxidation of lipids in low density lipoprotein particles.

This study was undertaken to understand further the mechanisms and dynamics of the oxidation of lipids in low density lipoprotein (LDL) particles, aiming specifically at elucidating the material balance between oxygen uptake and products found and also the relative susceptibilities to oxidation of cholesteryl ester in the core and phosphatidylcholine in the outer monolayer in the LDL particles. It was found that considerable amount of oxygen uptake could not be accounted for by conjugated diene or total peroxides. Total peroxide was measured from the phosphine oxide formed from triphenylphosphine or diphenyl-pyrenylphosphine by reduction of peroxides. Cholesteryl ester hydroperoxides and phosphatidylcholine hydroperoxides were the major peroxides formed in LDL oxidation, but they accounted for about 60% of total peroxide. Cholesterol was also oxidized, but its oxidation was significant only at the later stages of the reaction. It was also found that the oxidizability of cholesteryl ester relative to phosphatidylcholine was larger within the LDL particle than in homogeneous solution and this was interpreted in the context of the physical properties of LDL particle.

Cholesterol↗
PubMed1998

Dynamics of vitamin E action against LDL oxidation.

Vitamin E acts as an important antioxidant against oxidative modification of low density lipoprotein (LDL) which is accepted as an initial event in the pathogenesis of atherosclerosis. In spite of the numerous studies and reports, the action and role of vitamin E have not been fully elucidated yet. In this brief overview, the dynamics of action of vitamin E as an antioxidant have been discussed and it is emphasized that the total antioxidant potency is determined by the relative importance of many competing reactions which is determined by the reactivities and concentrations of substrates, radicals and antioxidant and by physical factors of the environment.

Animals↗
PubMed1997

Inhibition of oxidation of low-density lipoprotein by a novel antioxidant, BO-653, prepared by theoretical design.

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butyl-benzofuran (BO-653) is a novel antioxidant synthesized by theoretical designing based on the previous experimental findings and consideration. The antioxidant activities of BO-653 against the oxidative modification of low-density lipoprotein (LDL) induced by free radicals were studied. BO-653 was consumed faster than endogenous alpha-tocopherol and inhibited the formation of lipid hydroperoxides, which was observed during the consumption of alpha-tocopherol. Doxyl stearic acids incorporated into LDL as spin probes competed with the antioxidants in scavenging radicals. It was found that the efficacy of radical scavenging by alpha-tocopherol became smaller as the radical went deeper into the interior of LDL particle, whereas that by BO-653 did not change. Ascorbic acid in the aqueous phase spared alpha-tocopherol efficiently during oxidation. On the other hand, the sparing effect of ascorbic acid for BO-653 was not remarkable, unlike that for alpha-tocopherol, which implied different locations of radicals derived from BO-653 and alpha-tocopherol within the LDL particle. It was concluded that BO-653 protected LDL from oxidative modification efficiently by scavenging peroxyl radicals and by reducing alpha-tocopheroxyl radicals and that this novel antioxidant might act as a potent inhibitor of development of atherosclerosis.

Amidines↗
PubMed1997

Peroxynitrite-induced hemolysis of human erythrocytes and its inhibition by antioxidants.

It was found that human erythrocytes underwent hemolysis when incubated with peroxynitrite at 37 degrees C under air. The extent of hemolysis increased with increasing peroxynitrite concentration and decreasing hematocrit. The peroxynitrite-induced hemolysis was suppressed only partially by a radical scavenging antioxidant such as uric acid and Trolox, a water-soluble vitamin E analogue, but reduced glutathione, N-acetylcysteine and albumin efficiently inhibited the hemolysis. A selenium-containing organic compound, ebselen, also suppressed the hemolysis. On the other hand, nitric oxide and superoxide generated concomitantly from 3-morpholinosydnonimine (SIN-1) did not induce appreciable hemolysis, while it converted hemoglobin to methemoglobin extensively.

Acetylcysteine↗
PubMed1997

2,3-Dihydro-5-hydroxy-2,2-dipentyl-4,6-di-tert-butylbenzofuran: design and evaluation as a novel radical-scavenging antioxidant against lipid peroxidation.

To develop a novel potent radical-scavenging antioxidant, the ideal structure of a phenolic compound was designed considering the factors that determine antioxidant potency. 2,3-Dihydro-5-hydroxy-2,2-dipentyl-4, 6-di-tert-butylbenzofuran (BO-653) was thus synthesized and its antioxidant activity was evaluated against lipid peroxidations in vitro. The electron spin resonance study showed that the phenoxyl radical derived from BO-653 was more stable than alpha-tocopheroxyl radical. BO-653 reduced alpha-tocopheroxyl radical rapidly, but alpha-tocopherol did not reduce the phenoxyl radical derived from BO-653. However, the chemical reactivity of BO-653 toward peroxyl radical was smaller than that of alpha-tocopherol. This was interpreted as the steric effect of bulky tert-butyl groups at both ortho positions which hindered the access of peroxyl radical to the phenolic hydrogen. However, the tertbutyl substituents increased the stability of BO-653 radical and also lipophilicity, and its antioxidant potency against lipid peroxidation in phosphatidylcholine liposomal membranes was superior to that of alpha-tocopherol. Ascorbic acid reduced the phenoxyl radical derived from BO-653 and spared BO-653 during the oxidation of lipid in the homogeneous solution. On the other hand, ascorbic acid did not spare BO-653 in the oxidation of liposomal membranes. It was concluded that BO-653 is a potent novel radical-scavenging antioxidant.

Antioxidants↗
PubMed1997

Mechanisms and dynamics of antioxidant action of ubiquinol.

The mechanisms and dynamics of antioxidant action of ubiquinol have been studied. Ubiquinol scavenges peroxyl radical faster than alpha-tocopherol. However, it is autooxidized rapidly to give hydroperoxyl radical and/or superoxide and hence its antioxidant potency is smaller than that of alpha-tocopherol. The side chain of ubiquinol reduces the mobility between the membranes. It was concluded that ubiquinol acts as a potent antioxidant in combination with alpha-tocopherol.

Animals↗
PubMed1997

Oxidation of rat liver phospholipids: comparison of pathways in homogeneous solution, in liposomal suspension and in whole tissue homogenates.

The oxidation of equivalent concentrations of phospholipids in homogeneous solution, in multilamellar liposomal suspension, and in rat liver homogenate was carried out under aerobic conditions at 37 degrees C in order to examine the biochemical fate of oxidized phospholipids. Rat liver phospholipids were extracted with chloroform and methanol, and oxidation in this homogeneous solution was initiated with a lipid-soluble radical initiator. The oxidation products were phosphatidylcholine hydroperoxide (PC-OOH) and phosphatidylethanolamine hydroperoxide (PE-OOH), which were quantified by HPLC separation using a hydroperoxide-specific chemiluminescence detector. Co-extracted alpha-tocopherol and ubiquinol-9 suppressed the formation of PC-OOH and PE-OOH until oxidatively exhausted. The oxidation of extracted rat liver phospholipids in multilamellar liposomal suspension initiated with the lipid-soluble initiator gave similar results, but with slower rates of antioxidant depletion and phospholipid hydroperoxide formation due to a lower efficiency of free radical production in liposomal membranes. In contrast, the oxidation of rat liver homogenate containing active tissue enzymes initiated by the addition of either free radical initiators or tert-butyl hydroperoxide gave phosphatidylcholine hydroxide, phosphatidylethanolamine hydroxide, and free fatty acid hydroxides as oxidation products. Exogenous PC-OOH added to the rat liver homogenate was reduced to phosphatidylcholine hydroxide with subsequent hydrolysis to its free fatty acid hydroxide. These results suggest that peroxidase and phospholipase enzymes play important roles in the repair of oxidatively damaged phospholipids in biomembranes.

Animals↗
PubMed1997

Synthesis of monoesters of pyrroloquinoline quinone and imidazopyrroloquinoline, and radical scavenging activities using electron spin resonance in vitro and pharmacological activity in vivo.

Monoesters with the ester groups at C-2 of pyrroloquinoline quinone (PQQ) and C-9 of imidazopyrroloquinoline (IPQ) were synthesized, and radical scavenging activities of coenzyme PQQ, IPQ compounds synthesized from PQQ and various amino acids, and monoesters of PQQ and IPQ were studied in vitro and in vivo. PQQ and PQQ monoesters had strong radical scavenging activity using ESR in in vitro experiments. The IC50 value for superoxide (O2-) was from 1 to 6 x 10(-8) M and that for the hydroxy radical (.OH) was from 4 to 6 x 10(-5) M. IPQ compounds and IPQ monoesters also showed radical scavenging activity. These compounds prevented injury during in vivo experiments, such as hydrocortisone-induced cataracts, endotoxin shock and CCl4-induced liver injury (isolated hepatocytes and rats). Especially, the monoesters of PQQ and IPQ prevented liver injury in rats equally by oral or intraperitoneal administration. These results suggest that PQQ functions as a radical scavenging factor in addition to being a cofactor of quinoprotein enzymes, and monoesters with the ester groups at C-2 of PQQ and C-9 of IPQ are developed as treatment or preventive medicine for disease caused by radical compounds on the basis of strong radical scavenging activities, absorbability into cells, toxicity, safety and chemical stability.

Administration, Oral↗
PubMed1997

Effects of low dose X-ray irradiation on purine metabolism in mouse splenocytes.

This study examines the influence of low dose X-ray irradiation on purine nucleotide metabolites such as adenosine, inosine, hypoxanthine, xanthine and uric acid, and hence generation of ATP-mediated energy in mouse splenocytes. It was found that, unlike high dose irradiation which promotes membrane damage, low dose irradiation enhances the ability to regulate the energy metabolisms as reflected by the increase in Na+, K(+)-ATPase activity and the adequate activation of the above salvage pathway. Namely, the levels of adenosine, inosine and uric acid significantly increased, while the levels of xanthine and hypoxanthine decreased significantly. Moreover, the cysteine level and superoxide dismutase activity significantly increased at a dosage of 20 cGy.

Animals↗
PubMed1996

Reaction of phosphatidylcholine hydroperoxide in human plasma: the role of peroxidase and lecithin:cholesterol acyltransferase.

In order to elucidate the reason why phosphatidylcholine hydroperoxide is unstable in human plasma, 1-palmitoyl-2-linoleoylphosphatidylcholine hydroperoxide (PLPC-OOH) was incubated aerobically in human plasma at 37 degrees C, and its decomposition products were measured. The major product was the corresponding alcohol (PLPC-OH) and this reduction probably occurred by an enzymatic process since no acceleration in ascorbate depletion and no significant decrease in other plasma antioxidants were observed upon addition of PLPC-OOH. Cholesteryl linoleate hydroperoxide and its alcohol (Ch18:2-OH) were also detected as minor products. Similarly, 1-stearoyl-2-arachidonoylphosphatidylcholine hydroperoxide gave its alcohol (SAPC-OH) as a major product and cholesteryl arachidonate hydroperoxide and its hydroxide (Ch20:4=OH) as minor products. These oxidized cholesteryl esters are likely to be produced by the action of lecithin:cholesterol acyltransferase (LCAT) present in high-density lipoprotein (HDL) since (a) incubation of PLPC-OH and SAPC-OH in human plasma gave Ch18:2-OH and Ch20:4-OH, respectively, (b) isolated human HDL converted PLPC-OH to Ch18:2 OH and SAPC-OH to Ch20:4-OH while isolated human low-density lipoprotein was inactive for this conversion, and (c) formation of oxidized cholesteryl esters in plasma and HDL was inhibited by the LCAT inhibitor 5,5'-dithiobis(2-nitrobenzoic acid). A possible beneficial role of LCAT for converting phosphatdylcholine hydroperoxide to cholesteryl ester hydroperoxide is also discussed.

Adult↗
PubMed1996

Mechanism of lower oxidizability of eicosapentaenoate than linoleate in aqueous micelles.

The aerobic oxidation kinetics of methyl eicosapentaenoate (20:5n-3) and methyl linoleate (18:2n-6) were compared in homogeneous chlorobenzene solution and in Triton X-100 aqueous micelles at 37 degrees C. The rate of disappearance of 20:5n-3 was two times faster than that of 18:2n-6 in chlorobenzene, while the former was five times slower than the latter in aqueous micelles. It was also observed that delta O2 = delta 18:2n-6 and delta O2 = 2 delta 20:5n-3 in aqueous micelles. In the oxidation of a 1:1 mixture of 20:5n-3 and 18:2n-6 in micelles, the rate of disappearance of 20:5n-3 was 3.6 times faster than that of 18:2n-6, and the rate of total substrate disappearance was reduced by a factor of 5 as compared with 18:2n-6 oxidation. These data suggest that the peroxyl radical derived from 20:5n-3 is more polar than that from 18:2n-6, and the former is likely to diffuse from the core to the micelle surface. This lowers the oxidizability for 20:5n-3 in aqueous micelles by enhancing the termination reaction rate for peroxyl radicals and by reducing the rate of propagation since there may be more 20:5n-3 peroxyl radicals at the surface than in the micelle core.

Amidines↗
PubMed1996

Inhibition of oxidation of low density lipoprotein by troglitazone.

The effect of a new oral hypoglycemic agent troglitazone, (+/-)-5-[4-(6-hydroxy-2,5,7,8-tetramethylchroman-2-yl-methoxy)benz yl]-2,4-thiazolidinedione as an antioxidant against the free radical-mediated oxidation of low density lipoprotein (LDL) was studied. The oxidation of LDL gives cholesteryl ester hydroperoxide and phosphatidylcholine hydroperoxide as major primary products. Troglitazone incorporated exogenously into LDL inhibited the oxidations of LDL induced by either aqueous or lipophilic peroxyl radicals and suppressed the formation of lipid hydroperoxides efficiently. Ascorbic acid added into the aqueous phase spared both endogenous alpha-tocopherol and troglitazone in LDL. It was also found by absorption spectroscopic and electron spin resonance (ESR) studies that troglitazone reacted rapidly with a galvinoxyl radical to give a chromanoxyl radical which gives the same ESR spectrum as alpha-tocopherol. This ESR spectrum disappeared rapidly when ascorbic acid was added into the system. These results show that troglitazone acts as a potent antioxidant and protects LDL from oxidative modification.

Antioxidants↗
PubMed1996

Synthesis and aldose reductase-inhibitory activity of imidazopyrroloquinoline esters.

Derivatives of imidazopyrroloquinoline (IPQ) and its esters were synthesized. Some of these compounds potently inhibited aldose reductases of rabbit lens and dog kidney, as well as the human recombinant enzyme, though the coenzyme pyrroloquinoline quinone (PQQ) was a relatively poor inhibitor. The IPQ esters with a methyl substituent at the C-3 carboxyl group were less potent inhibitors than the analogs without esterification at this position. An IPQ ester with the free carboxyl group at C-3 inhibited sorbitol accumulation in rat red blood cells.

Aldehyde Reductase↗
PubMed1996

Inhibition of oxidation of low density lipoprotein by vitamin E and related compounds.

The oxidation of low density lipoprotein (LDL) was carried out aiming specifically at elucidating the anti-oxidant action of alpha-tocopherol. Lipophilic and hydrophilic azo compounds and copper induced the oxidation of LDL similarly to give cholesterol ester and phosphatidylcholine hydroperoxides as major products. The antioxidant potency of alpha-tocopherol in LDL was much poorer than in homogeneous solution. Doxyl stearic acids were used as spin probe and incorporated in LDL. The rate of reduction of doxyl nitroxide in LDL by ascorbate decreased with increasing distance from the LDL surface. From the competition between the spin probe and alpha-tocopherol in scavenging radical, it was found that the efficacy of radical scavenging by alpha-tocopherol became smaller as the radical went deeper into the interior of LDL. On the other hand, 2,2,5,7,8-pentamethyl-6-chromal spared the spin label regardless of the position of nitroxide. The antioxidant activity of chromanols against LDL oxidation increased with decreasing length of isoprenoid side chain at the 2-position. All these results were interpreted by location and low mobility of alpha-tocopherol in LDL. The tocopherol mediated propagation was observed notably at low rate of radical flux, but this was suppressed by reductant such as ascorbic acid and ubiquinol.

Amidines↗