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E Niki

Publications and source records attributed to E Niki.

At least 73 records · Page 4Linked to original sources

Action of beta-carotene as an antioxidant against lipid peroxidation.

The action and activity of beta-carotene as a radical-scavenging antioxidant against lipid peroxidation have been studied. beta-Carotene suppressed the free-radical-mediated oxidations of methyl linoleate in benzene solution and soybean phosphatidylcholine liposomal membranes in aqueous dispersions in a dose-dependent manner, but the antioxidant activity of beta-carotene was much smaller than that of alpha-tocopherol. beta-Carotene was 32 times less reactive toward peroxyl radical than alpha-tocopherol and approximately as reactive as 2,6-di-tert-butyl-4-methylphenol in benzene solution. Toward carbon-centered radical, beta-carotene was 11 times less reactive than alpha-tocopherol. When beta-carotene and alpha-tocopherol were present together in homogeneous solution, alpha-tocopherol was consumed predominantly and beta-carotene was spared. When they were incorporated simultaneously into the same dimyristoyl phosphatidylcholine liposomal membranes and the radicals were formed in the aqueous phase, alpha-tocopherol was consumed faster than beta-carotene, but the sparing efficacy was much smaller than in homogeneous solution. On the contrary, beta-carotene was consumed faster than alpha-tocopherol when the radicals were generated within the lipophilic compartment of the membranes, implying that beta-carotene is relatively more favorable than alpha-tocopherol for scavenging lipophilic radicals within the membranes. In contrast to an efficient synergistic inhibition by a combination of alpha-tocopherol and ascorbic acid, cooperative interaction between beta-carotene and ascorbic acid was not observed. beta-Carotene underwent autooxidation to give polymeric products and the rate of consumption of beta-carotene increased with increasing concentrations of itself and oxygen and decreased with increasing concentration of lipids. The formation of polymeric products was confirmed by gel permeation chromatography. It was concluded that beta-carotene is less potent as an antioxidant than alpha-tocopherol because beta-carotene is less reactive toward peroxyl radical than alpha-tocopherol and the stable beta-carotene radical reacts with oxygen to give beta-carotene peroxyl radical which is not stable but able to attack lipid to continue chain oxidation. The higher antioxidant activity of beta-carotene at lower oxygen pressure is attributed primarily to an unfavorable formation of beta-carotene peroxyl radical at higher oxygen pressure rather than a higher reactivity of beta-carotene toward carbon-centered radical than peroxyl radical.

Antioxidants↗

Action of nitric oxide as an antioxidant against oxidation of soybean phosphatidylcholine liposomal membranes.

To elucidate the protective role of nitric oxide (NO) against lipid peroxidation, the effect of NO donor on the formation of lipid hydroperoxide and consumption of alpha-tocopherol in the oxidation of soybean phosphatidylcholine liposomal membranes was studied. The oxidation was induced by either aqueous or lipophilic peroxyl radicals generated by the hydrophilic or lipophilic azo compound, respectively. It was found that NO acted as a potent antioxidant by scavenging peroxyl radicals rapidly. It was also found that NO was capable of penetrating multilamellar membranes to scavenge lipid peroxyl radicals and spare alpha-tocopherol.

Antioxidants↗

Hepatic damage induced by perfusion of radical generating azo compound and its inhibition by vitamin E.

The damaging effect of perfusion of hydrophilic radical generating azo compound on the liver of normal and vitamin E-deficient rats and its inhibition by antioxidants were studied in order to increase understanding of the action of free radicals on biological tissues. The hepatic damage was evaluated from the release of cytosolic enzymes such as glutamic oxaloacetic transaminase and glutamic pyruvic transaminase, mitochondrial oxidation metabolism and morphological change. Two kinds of hydrophilic azo compounds were used, one which decomposes spontaneously at a uniform rate to generate free radicals and the other which does not. The former induced hepatic damage in a dose-dependent manner, while the latter did not exert any damage. Both endogenous vitamin E in the membranes and a water soluble vitamin E analogue added simultaneously with a radical initiator suppressed the hepatic damage. These results show that the hepatic damage induced by perfusion of radical generating azo compound is caused not by the azo compound itself but by free radicals.

Alanine Transaminase↗

Alpha-tocopherol mediated peroxidation in the copper (II) and met myoglobin induced oxidation of human low density lipoprotein: the influence of lipid hydroperoxides.

The principal antioxidant in human LDL, alpha-tocopherol, is converted to the alpha-tocopheroxyl radical after reaction with peroxyl radicals or Cu2+, and, if it does not terminate with peroxyl radicals, could initiate lipid peroxidation; a phenomenon called 'tocopherol mediated peroxidation'. Only in the presence of Cu2+ and low levels of lipid hydroperoxides was an alpha-tocopherol dependent decrease in the resistance of LDL to oxidation detected. This suggests that tocopherol mediated peroxidation will probably not contribute significantly as a pro-oxidant process in those individuals most at risk of developing atherosclerosis through an oxidative mechanism.

Azoles↗

Interaction among vitamin C, vitamin E, and beta-carotene.

The effects of vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), and beta-carotene as antioxidants and their cooperative action against the oxidation of lipid in solution, membranes, and lipoproteins have been studied and reviewed. Ascorbic acid and alpha-tocopherol act as potent, and probably the most important, hydrophilic and lipophilic antioxidants, respectively. They function at their own site individually and furthermore act synergistically. beta-Carotene has lower reactivity toward radicals than does alpha-tocopherol and acts as a weak antioxidant in solution. It is more lipophilic than alpha-tocopherol and is assumed to be present at the interior of membranes or lipoproteins, which enables it to scavenge radicals within the lipophilic compartment more efficiently than does alpha-tocopherol. The cooperative interaction between vitamin C and vitamin E may be quite probable, that of vitamin C and beta-carotene is improbable, whereas that between vitamin E and beta-carotene may be possible.

Antioxidants↗

Dynamics of free radical formation from the reaction of peroxides with haemproteins as studied by stopped-flow chemiluminescence.

Metal ions such as iron and copper are implicated in the generation of free radicals in vivo, but the dynamics of free radical production in the decomposition of hydrogen peroxide and hydroperoxides by iron complexes have not been shown unequivocally due to their rapid rates. In the present study, we have devised a stopped-flow chemiluminescence system and succeeded in elucidating the time course of the free radical formation in the decomposition of hydrogen peroxide and organic hydroperoxides by haemproteins. The rate of free radical formation was very much dependent on the metal complexes and peroxides. Methemoglobin and cytochrome c decomposed hydrogen peroxide slower than microperoxidase but generated free radicals continuously. Methyl linoleate hydroperoxide was decomposed more rapidly than hydrogen peroxide. The chemiluminescence intensity was directly proportional to the amount of hydroperoxide, and the chemiluminescence progress curve reflected the time course of free radical flux. These results show that this stopped-flow chemiluminescence system is suitable to follow the radical flux from the decomposition of peroxides by metal ions.

Chromatography, High Pressure Liquid↗

Free radical-mediated oxidation of lipids induced by hemoglobin in aqueous dispersions.

In order to elucidate the effects of hemoglobin on the oxidative damage, the oxidations of soybean phosphatidylcholine (PC) liposomes and low density lipoprotein (LDL) in aqueous dispersions induced by ruptured erythrocytes (hemolysate) and methemoglobin were studied. The rate of oxidation of soybean PC liposomes induced by hemolysate was much faster than that induced by the same concentration of ferric sulfate or cupric chloride and increased with the increase in the amount of hemolysate. When soybean PC was treated beforehand with ebselen, which decomposes hydroperoxides but can not scavenge free radicals, the oxidation did not proceed. Furthermore, the oxidation was suppressed by the addition of pentamethylchromanol in liposomal membrane. The reaction of hemoglobin with methyl linoleate hydroperoxide in aqueous dispersions was also studied. It was found that hemolysate and methemoglobin decomposed the hydroperoxides much faster than cupric chloride and ferric sulfate. The electron spin resonance study strongly suggested that both hemolysate and methemoglobin decomposed hydroperoxides rapidly to form alkoxyl and peroxyl radicals. It was also found out by spectrophotometrical study and by using carbon monoxide and potassium cyanide that hemolysate was oxidized by organic hydroperoxide to form methemoglobin and ferrylhemoglobin. The rate of oxidation of LDL induced by hemolysate was much slower than that of soybean PC liposomes, while LDL was oxidized faster than soybean PC liposomes by cupric chloride under the same conditions. However, in the presence of tert-butyl hydroperoxide, the oxidation of LDL induced by hemolysate proceeded rapidly. These results were interpreted by both the chemical reactivity and the accessibility of metal catalyst to the lipid hydroperoxides in LDL and liposomes. It was suggested that hemoglobin released by hemorrhage might play a crucial role in the initiation of oxidative damage in vivo.

Erythrocytes↗

Effects of ebselen and probucol on oxidative modifications of lipid and protein of low density lipoprotein induced by free radicals.

The oxidative modification of low density lipoprotein (LDL) is accepted to be an important early event of atherosclerosis, but it has not yet been well understood. The preventive effects of two antioxidants with different functions, ebselen and probucol, against the oxidative modification of LDL induced by copper or a water-soluble radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) were studied in order to elucidate the mechanism of modification of apolipoprotein B-100 (apoB). Ebselen inhibited the copper-induced oxidation completely by reducing the hydroperoxides in LDL, since the initiation of copper-dependent oxidation requires the presence of a trace amount of hydroperoxides in LDL. On the other hand, ebselen did not suppress the oxidations of LDL induced by AAPH which generated free radicals by its thermal decomposition. The AAPH-induced oxidation of LDL in the absence of ebselen gave phosphatidylcholine hydroperoxide and cholesteryl ester hydroperoxide as major products, while in its presence, the hydroperoxides were reduced to corresponding alcohols. Interestingly, ebselen had little effect on the increase of relative electrophoretic mobility and fragmentation of intact apoB in the AAPH-induced oxidation. Probucol inhibited the oxidation of lipids in LDL effectively induced by either copper or AAPH, but the protein modifications were observed even in the presence of probucol. It was suggested that (1) lipid hydroperoxides do not play an important role in the modification of apoB such as increase in negative charge and fragmentation, (2) the direct attack of free radicals upon apoB and its modification by lipid oxidation products derived from hydroperoxides increase the negative charge of apoB, and (3) its fragmentation is caused primarily by an attack of free radicals.

Amidines↗

Interaction of alpha-tocopherol with copper and its effect on lipid peroxidation.

The interaction between alpha-tocopherol and copper ion and its effect on the oxidations of methyl linoleate micelles and soybean phosphatidylcholine liposomes in aqueous dispersions have been studied. alpha-Tocopherol reacted with copper in methanol with a rate constant estimated as 0.56 M-1s-1 at 37 degrees C. Similarly, alpha-tocopherol incorporated into methyl linoleate and ethyl palmitate micelles and also phosphatidylcholine liposomal membranes interacted with copper at roughly the similar rate. In every case, the formation of alpha-tocopheroxyl radical and reduction of cupric ion to cuprous ion were observed. Under these circumstances, alpha-tocopherol acted as a prooxidant rather than antioxidant. This interaction was also observed between endogenous alpha-tocopherol in human low density lipoprotein and copper, and the rate was estimated to be higher than that in methanol, implying the facile interaction of the two at LDL surface. However, copper incorporated in ceruloplasmin or chelated with albumin did not interact with endogenous alpha-tocopherol in LDL. It was concluded that alpha-tocopherol reacts with free copper(II) ion to give more reactive copper(I) ion and may act as a prooxidant for lipid peroxidation in the presence of free copper ion. However, such a prooxidant effect of alpha-tocopherol may not be important in vivo, where substantially all the copper ion must be sequestered.

Cations, Divalent↗

Effects of solvents and media on the antioxidant activity of alpha-tocopherol.

The effects of solvents and media on the antioxidant activity of alpha-tocopherol were studied. The antioxidant activities of alpha-tocopherol in different solvents decreased in the order of acetonitrile = hexane > ethanol = methanol, which indicates that the antioxidant activity of alpha-tocopherol is smaller in protic solvent than in aprotic solvent. The antioxidant activity of 2-(4,8,12-trimethyltridecyl)-5-hydroxy-2,4,6,7-tetramethylindan , which has similar structure to alpha-tocopherol but does not have ether oxygen, was also measured in protic and aprotic solvents. Its antioxidant activity was smaller than that of alpha-tocopherol in every solvent, but interestingly, substantially the same solvent effects were observed. These results show that the hydrogen bonding between the protic solvent and either oxygen is not important but that the hydrogen binding between protic solvent and phenolic group reduces the activity of alpha-tocopherol. Antioxidant activities of alpha-tocopherol in micelle system and liposomal membrane were markedly reduced compared with that in homogeneous solution. Solvent effect on the alpha-tocopheroxyl radical was also studied by using electron spin resonance. The hyperfine splitting constants of a5CH3H and a7CH3H were smaller in protic solvent than in aprotic solvent, which shows that lone-pair orbital energy on 5-CH3 and 7-CH3 is smaller in protic solvent. The ESR spectra of alpha-tocopheroxyl radical in liposomal membrane and micelle were similar to those observed in aprotic solvent and in protic solvent, respectively, suggesting that alpha-tocopheroxyl radical is located predominantly in the lipophilic domain of the liposomal membrane but in or closer to water phase of micelle aqueous suspensions.

Antioxidants↗

Antioxidative effects of dihydro-gamma-pyronyl-triterpenoid saponin (chromosaponin I).

Chromosaponin I (CSI), the naturally occurring form of soyasaponin I, inhibited the oxidation of soybean phosphatidylcholine liposomal membranes induced by a water-soluble radical initiator, 2,2'-azobis(2-amidinopropane) dihydrochloride. The antioxidative activity of CSI was similar to that of urate. Soyasaponin I, a degraded product of CSI, which has previously been thought to be an antioxidant, exerted no antioxidative activity.

Antioxidants↗

Effects of metal chelating agents on the oxidation of lipids induced by copper and iron.

The non-enzymatic oxidations of soybean phosphatidylcholine liposomes, methyl linoleate micelles and low-density lipoprotein in aqueous dispersions induced by copper and iron have been studied aiming specifically at elucidating the action of the metal chelating agents such as ethylenediaminetetraacetic acid disodium salt (EDTA), nitrilotriacetic acid (NTA), adenosine-5'-diphosphate disodium salt (ADP), desferrioxamine (DFO), penicillamine (PCM), and triethylene tetramine (TTM). The effects of chelators on chemiluminescence emitted from its probe luminol in the decomposition of tert-butyl hydroperoxide by metal ion were also studied. The effects of chelators on the oxidations depended both on the metal ion and the substrate. Namely, in the oxidations of both liposomes and micelles, EDTA and NTA suppressed the copper-induced oxidations, whereas they enhanced the oxidations induced by iron. ADP had little effect, while PCM and TTM had accelerating effect for both metal ions. On the other hand, in the oxidation of LDL, none of these chelators enhanced the oxidation. Especially, TTM and PCM suppressed the copper-induced oxidation of LDL, suggesting that the chelating agents blocked the access of the metal ion to the hydroperoxide within LDL. The effects of chelators on chemiluminescence emission were similar to those on the oxidations of liposomes and micelles. The cyclic voltammograms of metal complexes were also measured. The multiple effects of chelators on the rate of non-enzymatic, metal-catalyzed oxidations of lipids were interpreted by their influence on redox-potential and accessibility to hydroperoxide of the metal-chelator complex.

Chelating Agents↗

Dynamics of the oxidation of low density lipoprotein induced by free radicals.

Although the oxidation of low density lipoprotein (LDL) has been studied extensively, its dynamics have received much less attention. The present study was carried out aiming to elucidate the rates and products of the oxidation of LDL induced by free radicals generated in three different ways by hydrophilic and lipophilic azo radical initiators and copper. The oxidations were followed by measuring the formation of lipid oxidation products, the uptake of oxygen, consumption of vitamin E, and the fragmentation and acquisition of negative charge by apolipoprotein B within a single oxidation reaction. LDL was oxidized by a free radical chain mechanism independent of the manner of initiating free radical generation to give phosphatidylcholine hydroperoxide (PCOOH) and cholesteryl ester hydroperoxide (CEOOH) as major primary products. When the radicals were generated within the LDL compartment, CEOOH was formed almost exclusively and quantitatively at the initial stage. The kinetic chain length for the oxidation of cholesteryl ester was larger than that for phosphatidylcholine in the presence and absence of vitamin E even when the radicals were generated initially in the aqueous phase. PCOOH and CEOOH accumulated with increasing extent of oxidation, but then decreased at the later stage of oxidation. The decrease in hydroperoxides was more significant in copper-induced oxidations. The thiobarbituric acid reactive substances also increased with time, but they accounted for less than 10% of total oxygen uptake. Oxidative modification of apo B was also observed. The modification of apo B, that is, fragmentation and increase in negative charge correlated well with the oxidation of lipids independent of the manner of chain initiation. It was also suggested that some radicals formed in the aqueous phase attacked apo B directly. These results suggest the importance of chain propagation in the oxidative modification of LDL and also the lipophilic, chain-breaking antioxidants within LDL in its inhibition.

Apolipoproteins B↗

Plasma glutathione peroxidase reduces phosphatidylcholine hydroperoxide.

The reducing activity of rat plasma glutathione peroxidase on phosphatidylcholine hydroperoxide (PC-OOH) and cholesteryl ester hydroperoxide (CE-OOH) was examined since these hydroperoxides are the major oxidation products of plasma. PC-OOH was reduced by the enzyme while CE-OOH was not. The reduction of PC-OOH by the enzyme ceased when all thiol was consumed, but the activity was recovered by the addition of glutathione, suggesting glutathione is important to keep the enzyme in the reduced form. These results are consistent with the findings that CE-OOH is present in human and rat plasmas while PC-OOH is undetectable and suggest that one of the physiological roles of the enzyme is to reduce PC-OOH.

Animals↗

Inhibition of oxidative modification of low density lipoprotein by antioxidants.

Oxidation of LDL induced by free radicals proceeds by a chain mechanism to give phosphatidylcholine hydroperoxides and cholesteryl ester hydroperoxides as the major primary products. In addition, apolipoprotein B100 is also oxidized. Various antioxidants suppress the oxidative modification of LDL. Water-soluble radical-scavenging antioxidants such as vitamin C and uric acid act as the first defense to suppress the chain initiation. Lipophilic radical-scavenging antioxidants in LDL such as vitamin E and ubiquinol scavenge radicals attacking from outside and also within the LDL. The overall importance and potency of antioxidants depend not only on chemical reactivity but also on the physical factors such as location and mobility at the microenvironment in LDL.

Antioxidants↗