Inhibitory Effects of Ebselen on Lipid Peroxidation in Rat Liver Microsomes

The effects of ebselen(2-pheny1-1,2-benzoisoselenazol-3(2H)-one), a synthetic seleno-organic compound with glutathione peroxidase-like activity were investigated on lipid peroxidation in rat liver microsomes. Ebselen inhibited malondialdehyde production coupled to the lipid peroxidation stimulated by either ADP-iron-ascorbate or CC1₄. The inhibitory activity of ebselen on each system was strongly increased by a 5-min preincubation with liver microsomes; the IC₅₀ values against ADP-Fe-ascorbate-stimulated and CC1₄-stimulated lipid peroxidation were 1.6/jM and 70 μM respectively. Ebselen also inhibited the endogenous lipid peroxidation with a NADPH-generating system, but it slightly stimulated the endogenous activity of ADP-Fe-ascorbate-stimulated lipid peroxidation (without a NADPH-generating system). Furthermore, ebselen inhibited oxygen uptake coupled to the lipid peroxidation by ADP-Fe-ascorbate and NADPH-ADP-iron; the IC₅₀ values were 2.5μM AND 20.3 μM respectively. Ebselen also prolonged the lag-time of onset of ADP-Fe-ascorbate-stimulated lipid peroxidation significantly, but not that observed with NADPH-ADP-Fe-stimulated lipid peroxidation.     

年龄相关性白内障晶状体脂质过氧化及抗氧化能力的变化

摘要目的：观察年龄相关性白内障晶状体中脂质过氧化及抗氧化能力的变化,探讨脂质过氧化与年龄相关性白内障的关系。方法：选择2010年8月至2011年10月我院收治的年龄相关性白内障患者35例（35眼）和透明晶状体15例（15眼）作为白内障纽和对照组,测定其维生素C（VitC）、脂质过氧化物丙二醛（MDA）含量及超氧化物歧化酶（SOD）活性的改变。结果：与对照组相比,白内障组晶状体内VitC含量和SOD酶活性均显著下降,分别降低了39．30％（P〈0．01）和63．50％（P〈0．01）,MDA含量较明显升高（P〈O．01）。Pearson相关分析显示,对照组透明晶状体中MDA含量与SOD活性、VitC含量均呈显著负相关（r=-0．858,P〈0．01;r-=．0．883,P〈0．01）,而白内障组晶状体中三者未发现明显的直线相关关系（P〉0．05）。结论：脂质过氧化参与了年龄相关性白内障的形成,SOD和VitC对晶状体氧化损伤具有一定的保护作用。     

Lipid Peroxidation in Choline-Methionine Deficiency

A deficiency of choline and methionine is hepatocarcinogenic and is associated with an apparent increase in lipid peroxidation. In this study the susceptibility of microsomes and nuclei to ferritin-dependent lipid peroxidation is examined together with the status of the peroxidation- protective systems. Choline-methionine deficiency caused an increase in Se-independent GSH peroxidases (GSH transferase subunit 2) and membrane vitamin E but a decrease in Se-dependent GSH peroxidase and microsomal GSH peroxidase activity. Choline-methionine deficient microsomes and nuclei were 4-fold more susceptible to lipid peroxidation induced in vitro by physiological concentrations of ferritin/ascorbate/ADP; and the peroxidation was less effectively inhibited by GSH and soluble GSH peroxidases than controls. The results indicate that a decreased level of Se-dependent and membrane GSH peroxidases is involved in the increase in lipid peroxidation observed in choline-methionine deficiency.     

Lipid Peroxidation and Antioxidant Systems in Rat Brain: Effect of Chronic Alcohol Consumption

The effect of chronic ethanol exposure, in a liquid diet, on lipid peroxidation and some antioxidant systems of rat brain was investigated. Chronic ethanol administration induced a greater susceptibility to iron/ascorbate-induced lipid peroxidation, estimated as thiobarbituric reactive substances (TBARS) production, in the microsomal fraction, but a lower lipid peroxidation in the total homogenate. Glutathione (GSH) levels as well as GSH peroxidase and GSH reductase were unaffected, while the activity of Cu-Zn superoxide dismutase was decreased and that of catalase increased. Lipid peroxidation experiments performed in the presence of some hydroxyl radical scavengers suggested that a greater OH^· generation may be responsible of the greater TBARS production in the microsomal fraction of ethanol treated rats; differently, in total homogenate of control and ethanol rats a relationship was found between the redox state of iron and TBARS production, suggesting that the lower lipid peroxidation in treated rats may depend on a different modulation of the iron redox state.     

Antioxidant Properties of New Chalcogenides Against Lipid Peroxidation in Rat Brain

Ebselen (2-phenyl- 1,2-benzisoselenazole-3 (2H)-one) is a seleno-organic compound with antioxidant properties, and anti-inflammatory actions. Recently, ebselen improved the outcome of acute ischemic stroke in humans. In the present study, the potential antioxidant capacity of organochalcogenide compounds diphenyl diselenide (PhSe)₂, diphenyl ditelluride (PhTe)₂, diphenyl disulfide (PhS)₂, p-Cl-diphenyl diselenide (pCl-PhSe)₂, bis-[S-4-isopropyl 2-phenyl oxazoline] diselenide (AA-Se)₂, bis-[S-4-isopropyl 2-phenyl oxazoline] ditelluride (AA-Te)₂ and bis-[S-4-isopropyl 2-phenyl oxazoline] disulfide (AA-S)₂ was compared with that of ebselen (a classical antioxidant). Spontaneous and quinolinic acid (QA)- (2 mM) and sodium nitroprusside (SNP)- (5 M)-induced thiobarbituric reactive species (TBARS) production by rat brain homogenates was determined colorimetrically. TBARS formation was reduced by ebselen, (PhSe)₂, (PhTe)₂, (AA-Se)₂, (AA-S)₂ and (pCl- PhSe)₂ to basal rates. The concentrations of these compounds needed to inhibit TBARS formation by 50% (lC₅₀) are 1.71 M, 3.73 M, 1.63 M, 9.85 M, > 33.3 M, 23.2 M and 4.83 M, respectively for QA. For TBARS production induced by SNP the lC₅₀ was 2.02 M, 12.5 M, 2.80 M, > 33.3 M, 24.5 M and 7.55 M, respectively. The compounds (AA-Te)₂ and (PhS)₂ have no antioxidant activity and pro-oxidant activity, respectively. These results suggest that (AA-Se)₂ and (AA-S)₂ can be considered as potential pharmaceutical antioxidant agents.     

Lipid Peroxidation In Vivo Induced by Reversible Global Ischemia in Rat Brain

It has been hypothesized that ischemia, followed by reperfusion, facilitates peroxidative free-radical chain processes in brain. To resolve this question, rats were subjected to reversible global ischemia. From coronal sections of brains frozen in situ, small (ca. 2 mg) amounts of tissue were sampled from neocortex, hippocampus, and thalamus of both cerebral hemispheres of four groups of rats exposed to 30 min cerebral ischemia followed by 0, 30, 60, and 240 min of reperfusion, and from a control group subjected to the same operative procedures, except for the induction of ischemia. Heptane-solubilized total lipid extracts from these samples were analyzed spectroscopically in the 190-330 nm range for content of isolated (nonconjugated) double bonds and of conjugated diene structures; the latter are formed from isolated double bonds during peroxidation of unsaturated fatty acids. Spectra derived from tissue regions of rats subjected to ischemia, or ischemia followed by reperfusion, were compared to averaged, region-specific control spectra and were normalized to the original content of isolated double bonds in the peroxidized samples. The resultant difference spectra were analyzed in terms of ratios of conjugated diene concentration to the concentration of isolated double bonds originally at risk in the specific tissue zones considered. The peak representing conjugated diene formation was centered at 238 +/- 1 nm and was usually well resolved when the molar ratio [conjugated diene]/[isolated double bonds], expressed as a percentage [( CD]/[IDB]), was greater than 0.25%.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of Vitamin A and Its Analogs on Nonenzymatic Lipid Peroxidation in Rat Brain Mitochondria

Vitamin A (retinol) and some of its analogs exhibited varying degrees of inhibition on induced iron and ascorbic acid lipid peroxidation of rat brain mitochondria. Malonyldialdehyde production was used as an index of the extent of in vitro lipid peroxidation. The fat-soluble vitamins retinol, retinol acetate, retinoic acid, retinol palmitate, and retinal at concentrations between 0.1 and 10.0 mmol/L inhibited brain lipid peroxidation. Retinol and retinol acetate were the most effective inhibitors. It is concluded from this study that retinol and its analogs can be considered as potential antioxidant factors, more potent than some of the well-known antioxidants such as alpha-tocopherol and butylated hydroxytoluene.     

Effect of Fish Oil and Coconut Oil on Antioxidant Defence System and Lipid Peroxidation in Rat Liver

Diets high in fish oil containing polyunsaturated fatty acids of the n-3 family. have been suggested to decrease the risk of cardiovascular disease. However these lipids are highly susceptible to oxidative deterioration. In order to investigate the influence of n-3 fatty acids on oxidative status, the effect of feeding rats with fish oil or cocunut oil diets was studied by measuring different parameters related to an oxidative free radical challenge. Synthetic diets containing 15% (w/v) fish oil or coconut oil were used to feed growing rats for 4 weeks. As compared to control diet, the fish oil containing diet produced a significant decrease of cholesterol and triglyceride concentration in serum. however there was a significant increase in lipid peroxidation products. In addition, in fish oil fed animals, there was also a decrease in vitamin E and A concentration. Furthermore, the rate of lipid peroxidation in isolated microsomes was three fold higher in rats fed fish oil as compared to rats with coconut oil diet. No significant differences between the two experimental groups were observed in superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activities. However, there was a decrease in glutathione peroxidase (GPX) activity. These results suggest that fish oil feeding at an amount compatible with human diet, although decreasing plasma lipids, actually challenge the antioxidant defence system, thus increasing the susceptibility of tissues to free radical oxidative damage.     

Antimalarial Drugs Exacerbate Rat Liver Microsomal Lipid Peroxidation in the Presence of Oxidants

The study was undertaken to evaluate the effect of prior treatment of rats with the antimalarial drugs amodiaquine (AQ) mefloquine (MQ) and halofantrine (HF) on rat liver microsomal lipid peroxidation in the presence of 1 mM FeSO4, 1 mM ascorbate and 0.2 mM H₂O₂ (oxidants). Ingestion of -tocopheral, a radical chain-breaking antioxidant was also included to assess the role of antioxidants in the drug treatment. In the presence of oxidants AQ, MQ and HF elicited 288%, 175% and 225% increases in malondialdehyde (MDA) formation while the drugs induced 125%, 63% and 31% increases in the absence of oxidants respectively. Similarly, AQ, MQ and HF induced lipid hydroperoxide formation by 380%, 256%, 360% respectively in the presence of oxidants and 172%, 136% and 92% in the absence of exogenously added oxidants respectively. -tocopherol reduced AQ, MQ and HF-induced MDA formation by 40%, 55% and 52% respectively and lipid hydroperoxide formation by 53%, 59% and 54% respectively. Similarly, -tocopherol attenuated the AQ, MQ and HF-induced MDA formation by 49%, 51% and 51% in the presence of oxidants and lipid hydroperoxide formation by 61%, 62% and 47% respectively. The results indicate that rat liver microsomal lipid peroxidation could be enhanced by antimalarial drugs in the presence of reactive oxygen species and this effect could be ameliorated by treatment with antioxidants.     

Effect of Fish Oil and Coconut Oil on Antioxidant Defence System and Lipid Peroxidation in Rat Liver

Diets high in fish oil containing polyunsaturated fatty acids of the n-3 family. have been suggested to decrease the risk of cardiovascular disease. However these lipids are highly susceptible to oxidative deterioration. In order to investigate the influence of n-3 fatty acids on oxidative status, the effect of feeding rats with fish oil or cocunut oil diets was studied by measuring different parameters related to an oxidative free radical challenge. Synthetic diets containing 15% (w/v) fish oil or coconut oil were used to feed growing rats for 4 weeks. As compared to control diet, the fish oil containing diet produced a significant decrease of cholesterol and triglyceride concentration in serum. however there was a significant increase in lipid peroxidation products. In addition, in fish oil fed animals, there was also a decrease in vitamin E and A concentration. Furthermore, the rate of lipid peroxidation in isolated microsomes was three fold higher in rats fed fish oil as compared to rats with coconut oil diet. No significant differences between the two experimental groups were observed in superoxide dismutase (SOD) and phospholipid hydroperoxide glutathione peroxidase (PHGPX) activities. However, there was a decrease in glutathione peroxidase (GPX) activity. These results suggest that fish oil feeding at an amount compatible with human diet, although decreasing plasma lipids, actually challenge the antioxidant defence system, thus increasing the susceptibility of tissues to free radical oxidative damage.     

果醋对高脂小鼠血脂和肝脏脂质过氧化的影响

本文目的在于研究果醋对高脂小鼠血脂和肝脏脂质过氧化的影响。长期饲喂高脂饲料造成小鼠高血脂和肝脏脂质过氧化模型,预防性给予果醋,测定血清中总胆固醇（TC）,甘油三酯（TG）,低密度脂蛋白胆固醇（LDL-C）和高密度脂蛋白胆固醇（HDL-C）的含量;测定肝脏中脂质过氧化终产物丙二醛（地A）的含量和超氧化物歧化酶（SOD）的活性。结果证明果醋可以明显降低高脂小鼠血清中TC,LDL含量和肝脏组织中MDA含量,提高肝脏组织SOD活性。     

Dietary Modulation of Plasma Bilirubin and of Hepatic Microsomal Lipid Peroxidation in the Gunn Rat

An in vitro assay for the simultaneous measurement of lipid peroxidation (LPO) and bilirubin degradation BRD) activities in rat liver microsomes has been developed; a good correlation between the 2 activities was observed (r = 0.78). In the Gunn rat a lipid free diet caused an increase in plasma bilirubin (62.4 ± 25.8%, n = 6) and a concomitant decrease in both hepatic microsomal LPO and BRD to zero. In contrast, on a 25% lipid diet there was a decrease in plasma bilirubin (46.1 ± 3.6%; n = 8) associated with an increase in LPO (1.26 ± 0.11 nmol/min/mg protein, and BRD (0.21 ± 0.6 nmol/min/mg protein). Therefore, in the absence of bilirubin glucuronidation, dietary modulation of plasma bilirubin and lipid peroxidation appear to be closely associated.     

Hypoxia-Induced Lipid Peroxidation in Rat Brain and Protective Effect of Carnitine and Phosphocreatine

The exposure to hypobaric hypoxia increased lipid peroxidation (as indicated by thiobarbituric acid-reactive substances [TBARS] in rat brain. Plasma lactate/pyruvate ratio was used as a marker of hypoxia. We compared the protective effect of -tocopherol with the effect of l-carnitine or phosphocreatine. Rats pretreated with -tocopherol, l-carnitine, or phosphocreatine had lower TBARS levels after the exposure to hypobaric hypoxia. However, lactate/pyruvate ratio was improved only in rats pretreated with l-carnitine or phosphocreatine. We conclude from our data that, contrary to -tocopherol, protective effects of l-carnitine and phosphocreatine administrations are due to their regulation of metabolic reactions during hypobaric hypoxia rather than to their scavenger activity.     

UVB对水稻幼苗膜脂过氧化作用的影响

ＵＶ－Ｂ处理的水稻幼苗,叶片的膜透性、Ｏ２－净产生速率及ＭＤＡ含量显著增加。在ＵＶ－Ｂ处理初期,活性氧防御系统中的ＳＯＤ和ＣＡＴ活性比对照增强,但随着处理时间的延长,ＳＯＤ和ＣＡＴ活性明显下降;ＰＯＤ活性受ＵＶ－Ｂ处理抑制。这一结果表明,ＵＶ－Ｂ降低了细胞内活性氧自由基的清除能力,膜脂过氧化作用加剧,最终导致伤害效应。     

Erythrocyte Lipid Peroxidation and Antioxidants in Gastric Cancer Patients

The present study has analysed the relationship between lipid peroxidation and antioxidant status in erythrocytes from 24 adult male gastic cancer patients and an equal number of age- and sex-matched normal subjects. Erythrocyte lipid peroxidation was markedly increased. Both enzymic and non-enzymic antioxidants were decreased in erythrocytes of gastric cancer patients. The present study highlights the occurrence of lipid peroxidation and possible breakdown of antioxidant status in patients with gastric carcinoma. © 1997 John Wiley & Sons, Ltd.     

大豆下胚轴线粒体的衰老与膜脂的过氧化作用

离体的大豆下胚轴线粒体,在人工衰老条件下,产生了结构膨胀和细胞色素氧化酶活性的下降。衰老的线粒体也发生膜脂的过氧化作用——丙二醛、脂质的氢过氧化物和荧光脂褐色素明显增加。而且,线粒体衰老时产生的膜脂过氧化产物雨二醛,可能是膜脂的磷脂酰胆碱和磷脂酰乙醇胺中的亚麻酸发生过氧化反应的结果。     

镉诱导的菊芋幼苗膜脂过氧化和抗氧化酶活性及过氧化物酶同工酶的改变

用含有不同浓度(0~400μmol/L)Cd(NO3)2的Hoagland营养液处理砂培的菊芋。处理50d后,测定植物体内镉积累量以及过氧化物酶(POD)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性,并对POD同工酶进行电泳分析。发现在Cd50~100μmol/L浓度内,随着镉浓度的升高,菊芋根和叶中镉的积累量显著增加,而随后积累量的增加有所减少。根和叶中MDA含量显著上升,说明镉引起了膜脂过氧化。0~100μmol/LCd处理,根和叶中POD活性随Cd浓度增加而增强,而在200~400μmol/LCd处理下有所减弱。根和叶SOD活性在50~200μmol/LCd处理下随Cd浓度增加而增强,而在400μmol/LCd处理下SOD活性明显受到抑制。根和叶CAT活性随Cd浓度升高而增强。电泳结果显示,POD同工酶变化明显,镉诱导出一条新酶带LP10。菊芋POD同工酶可以作为镉污染的土壤的生物指示剂。     

生物系统中脂质过氧化检测方法的评述

生物体系中脂质过氧化的检测方法是脂质过氧化反应机理研究能否取得成功的关键因素之一.检测生物体系中脂质过氧化的方法有多种,但各种检测方法在不同的实验中都显示出一定的优缺点,近年来应用较多并且很有前途的实验方法是高压液相色谱法以及化学发光法等.     

Protective Effect of Dehydroepiandrosterone Against Copper-Induced Lipid Peroxidation in the Rat

This study investigates the effectiveness and multitargeted activity of dehydroepiandrosterone (DHEA) as antioxidant in vivo. A single dose of DHEA was given IP to male rats. Liver and brain microsomes, and plasma low density lipoprotein (LDL), were isolated from rats sacrified 17 h later. Liver and brain microsomes were challenged with CuSO₄ and, as index of lipid peroxidation, the production of thiobarbituric acid reactive substances (TBARS) was measaured. Also, plasma low-density lipoprotein (LDL) were challenged with copper and the time course of lipid peroxidation was evaluated following the formation of conjugated dienes. The onset of TBARS generation induced by copper was marked delayed in both liver and brain microsomes from DHEA-treated animals. Also, the resistance of LDL to oxidation, expressed by the duration of the lag-phase of the kinetic curve, was significantly enhanced in DHEA-treated rats. Results indicate that in vivo DHEA supplementation makes subcellular fractions isolated from different tissues and plasma constituents (LDL) more resistant to lipid peroxidation triggered by copper. The antioxidant effect on plasma LDL might be of special relevance to the proposed antiatherogenic activity of DHEA. Moreover, multitargeted antioxidant activity of DHEA might protect tissues from oxygen radicals damage. © 1997 Elsevier Science Inc.     

Vanadyl-and Vanadate-Induced Lipid Peroxidation in Mitochondria and in Phosphatidylcholine Suspensions

Vanadyl (V_(IV)) was found to induce rapidly developing lipid peroxidation in intact and sonicated mitochondria as well as in phosphatidylcholine suspension. The ability of vanadate (V_(V)) to induce lipid peroxidation was much less pronounced compared to that of vanadyl. The peroxidative action of vanadate on phosphatidylcholine much increased in the presence of NADH and ascorbate. Preincubation of vanadate with glucose had the same effect.

Vanadyl-induced lipid peroxidation was not essentially influenced by SOD, catalase and ethanol but was completely inhibited by butylated hydroxytoluene.

All these effects of vanadyl and vanadate are thought to participate in the insulin-like and other biological actions of vanadium.