Glutathione Depletion in Isolated Hepatocytes: Its Relation to Lipid Peroxidation and Cell Damage

Abstract The effects of glutathione depletion in isolated hepatocytes have been studied. A list of compounds which depleted glutathione and induced lipid peroxidation and cell lysis is given. The effects of halogenated acetamides were studied in more detail and results of studies on the interaction of iodoacetamide with cellular constituents are presented. A single metabolite of iodoacetamide, tentatively identified as the glutathione conjugate, was excreted from the cells while less than one percent of the “parent compound” was retained, tightly bound to macromolecules. This bound component could not be associated with the cellular damage. Methionine, cysteine and α-tocopherol, as well as paracetamol and ethylmorphine, were found to prevent lipid peroxidation and lysis. It is concluded that GSH deficiency per se can lead to lipid peroxidation and that this reaction caused the observed hepatocellular lysis.     

Inhibitory Action of some Flavonoids on Enhanced Spontaneous Lipid Peroxidation Following Glutathione Depletion.

Depletion of hepatic glutathione in phenobarbital-induced rats by phorone (diisopropylidene acetone) led to an enhancement of spontaneous lipid peroxidation IN VITRO. Addition of exogenous glutathione, dithiocarb or one of the flavonoids (+)-catechin, (-)-epicatechin, 3-O-methylcatechin, quercetin, taxifolin, rutin, naringin or naringenin led in every case to a dose-dependent inhibition of this peroxidative activity. The concentration values yielding 50% inhibition (I (50)) varied from 1.0 x 10 (-6) M for glutathione to 1.9 x 10 (-5) M for naringenin. Naringin and naringenin, which lack the 3'-OH-group, were the least active inhibitors. The only structural feature of the flavonoids which affects their antioxidative action appears thus to be the 3',4'-dihydroxy-grouping.     

Effects of Antioxidants on Oxygen Toxicity in Vivo and Lipid Peroxidation in Vitro

Abstract: Convulsions and pulmonary damage result when animals are exposed to hyperbaric oxygen at pressures above about 300 kPa. Several hydroxyl radical scavengers (namely dimethylsulphoxide, dimethylthiourea and mannitol), the iron chelator desferoxamine and the lipid antioxidant butylated hydroxytoluene were tested for possible protection against such hyperbaric oxygen toxicity. Dimethylthiourea and dimethylsulphoxide prolonged the latency to the first convulsion, but, surprisingly, dimethylthiourea very significantly increased pulmonary damage at both pressures used (515 and 585 kPa). Desferoxamine also slightly increased lung damage at 585 kPa. Other antioxidants did not alter neurotoxicity or pulmonary toxicity induced by hyperbaric oxygen at 515 or 585 kPa. The antioxidants were also tested for their ability to inhibit lipid peroxidation (TBARS formation) in vitro. Desferoxamine (5 and 50 μM), and butylated hydroxytoluene (0.1 mM and 1 mM) greatly inhibited TBARS formation in brain and lung homogenates incubated at 37°. None of the hydroxyl radical scavengers affected TBARS levels in homogenates. There was no correlation between in vitro inhibition of lipid peroxidation and in vivo protection against oxygen toxicity.     

Protective Effects of Phytochemical Antioxidants Against Neurotoxin-Induced Degeneration of Dopaminergic Neurons

The specific toxicity to dopaminergic neurons of psychostimulants and neurotoxins has been extensively studied in vivo and in vitro, and findings have been used to establish animal models of amphetamine psychosis or Parkinson’s disease. The multiple mechanisms of neurotoxicity operating in these disorders are known to involve oxidative stress or neuroinflammation, producing the characteristic behavioral and neuropathlogical changes arising from injured dopaminergic neurons and glial cells. A number of studies have shown that glia-targeting antioxidants play important roles in protecting against the neurotoxicity caused by psychostimulants or neurotoxins. Phytochemicals, which are non-nutritive plant chemicals, protect dopaminergic neurons and glial cells from damage caused by psychostimulants or neurotoxins. The objective of this review was to evaluate the involvement of glial cells in dopaminergic neuron–specific toxicity and to explore the neuroprotective activity of phytochemicals in terms of anti-inflammatory and antioxidant action.     

Protective Effects of Salicylic Acid and Vitamin C on Sulfur Dioxide-Induced Lipid Peroxidation in Mice

The antioxidant effects of exogenous salicylic acid (SA) and vitamin C (Vit C) on the oxidative stress induced by 56 mg/m³ of sulfur dioxide (SO₂) in mouse livers and brains were investigated. The exposure of SO₂ caused significant elevation of thiobarbituric acid-reactive substance (TBARS) levels and reduction of enzyme activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in brain and liver, accompanied by a decrease in relative growth rate, when compared with controls. Application of moderate concentrations of SA and Vit C markedly reduced the SO₂-induced elevation of TBARS levels, with 5.5 mg/kg SA or 200 mg/kg Vit C being most effective. In contrast to the decrease of TBARS levels, the levels of SOD, POD, and CAT in liver and brain were significantly increased in comparison with controls. The polyacrylamide gel electrophoresis (PAGE) of total liver proteins showed that the SO₂ inhalation caused a 30-kD protein band disappearance compared with the control. However, the band remained unchanged in the samples treated with 5.5 and 8.25 mg/kg SA or 100, 200, and 400 mg/kg Vit C. Therefore, this protein band may serve as a marker for the damage induced by SO₂ and an additional basis for drug screening and selection.     

家兔肾上腺素性心律失常时脂质过氧化的损伤及西米替丁的保护作用

采用硫代巴比妥酸（ＴＢＡ）显色法测定肾上腺素（ａｄｒｅｎａｌＡｄｒ）致室性心律失常（ＶＡ）后血浆及组织匀浆中脂质过氧化物（ＬＰＯ）的代谢产物丙二醛（ＭＤＡ）的含量,观察西米替丁（ｃｉｍｅｔｉｄｉｎｅＣｉｍ）对其含量的影响。结果发现Ａｄｒ诱发家兔ＶＡ后血浆及组织匀浆中ＭＤＡ含量明显增加,Ｃｉｍ３７．５ｍｇ／ｋｇｉｖ,能明显降低ＶＡ的发生率,推迟ＶＡ发作的时间,缩短其持续时间,并能显著抑制ＭＤＡ生成。提示Ａｄｒ致ＶＡ后体内脂质过氧化过程加强,Ｃｉｍ抗脂质过氧化可能与抗心律失常作用有关。     

Influence of Garlic Extract on Temporal Characteristics of Lipid Peroxidation Products and Antioxidants in Tumor-Bearing Rats

ABSTRACT

Effects of garlic (Allium sativum. L.) extract on the temporal patterns of circulatory lipid peroxidation products and antioxidants during N.-nitrosodiethylamine (NDEA)-induced hepatic tumorigenesis were investigated in Wistar rats. Experimental animals were divided into control, NDEA-treated, NDEA + garlic-treated, and garlic-treated. The characteristics of circadian rhythms (acrophase, amplitude, and mesor) of lipid peroxidation products (thiobarbituric acid reactive substances) and antioxidants (reduced glutathione, glutathione peroxidase, superoxide dismutase, and catalase) were analyzed. Alterations in the temporal characteristics of all variables were observed in NDEA-treated rats when compared to other groups. The alterations in the characteristics of these variables in NDEA-treated and in other groups deserve further investigation for the prognosis and therapeutic efficacy of chronotherapy of cancer.     

Experimental Exposure to Wood-Smoke Particles in Healthy Humans: Effects on Markers of Inflammation,Coagulation, and Lipid Peroxidation

Particulate air pollution is known to increase cardiovascular morbidity and mortality. Proposed mechanisms underlying this increase include effects on inflammation, coagulation factors, and oxidative stress, which could increase the risk of coronary events and atherosclerosis. The aim of this study was to examine whether short-term exposure to wood smoke affects markers of inflammation, blood hemostasis, and lipid peroxidation in healthy humans. Thirteen subjects were exposed to wood smoke and clean air in a chamber during two 4-h sessions, 1 wk apart. The mass concentrations of fine particles at wood smoke exposure were 240–280 μg/m³, and number concentrations were 95,000–180,000/cm³. About half of the particles were ultrafine (< 100 nm). Blood and urine samples were taken before and after the experiment. Exposure to wood smoke increased the levels of serum amyloid A, a cardiovascular risk factor, as well as factor VIII in plasma and the factor VIII/von Willebrand factor ratio, indicating a slight effect on the balance of coagulation factors. Moreover, there was an increased urinary excretion of free 8-iso-prostaglandin_2α, a major F₂-isoprostane, though this was based on nine subjects only, indicating a temporary increase in free radical-mediated lipid peroxidation. Thus, wood-smoke particles at levels that can be found in smoky indoor environments seem to affect inflammation, coagulation, and possibly lipid peroxidation. These factors may be involved in the mechanisms whereby particulate air pollution affects cardiovascular morbidity and mortality. The exposure setup could be used to establish which particle characteristics are critical for the effects.     

茶多酚对脑缺血再灌注损伤的保护作用及在体外抗脂质过氧化和清除自由基作用

目的 :研究茶多酚对脑缺血再灌注损伤的保护作用及抗脂质过氧化和清除自由基的作用。方法 :结扎大鼠双侧颈总动脉及迷走神经后 ,再灌注 4 5min ,建立脑缺血再灌注模型。由自由基诱导的脑线粒体脂质过氧化 ,用硫代巴比妥酸法测定。由Xan XO诱导的O 2 and由Fe2 + H2 O2 诱导的·OH ,用紫外分光光度仪测定。结果 :在脑缺血再灌注损伤时 ,茶多酚能改善SOD、GSH Px、CAT活性 (P <0 0 1) ,同时降低脑水肿和MDA含量 (P <0 0 1和P <0 0 5 )。茶多酚具有明显的清除·OH和O 2 的作用 (IC50 分别为 2 2mmol·L-1和 1 9mmol·L-1) ,茶多酚明显抑制由·OH诱导脑线粒体脂质过氧化 ,并呈浓度依赖性。结论 :结果提示茶多酚能保护脑缺血再灌注损伤 ,与其清除自由基和抗脂质过氧化作用有关     

Tissue Changes in Glutathione Metabolism and Lipid Peroxidation Induced by Swimming are Partially Prevented by Melatonin

Abstract: The present study used male Sprague-Dawley rats to investigate changes in glutathione [reduced (GSH) and oxidized GSH (GSSG)], lipid peroxidation (as indicated by tissue levels of malonaldehyde and 4-hydroxyalkenals), and the activity of the antioxidant enzyme glutathione peroxidase after a bout of swimming (30 min.) with or without melatonin (N-acetyl-5-methoxytryptamine) treatment. In muscle, the concentration of GSH and the GSH/GSSG ratio were decreased following 30 min. of swimming; these changes are indicative of enhanced oxidative stress. Pretreatment with melatonin prevented these effects. In liver, swimming increased significantly both GSH and GSSG, and decreased the GSH/GSSG ratio. When animals were treated with melatonin, concentrations of GSH and GSSG were also increased after swimming; however, the reduction in the GSH/GSSG ratio was prevented by melatonin. Brain GSH/GSSG ratio was not affected by exercise or by melatonin. Swimming enhanced the levels of lipid peroxidation products is muscle; this was prevented in animals treated with melatonin. Glutathione peroxidase activity was significantly elevated after swimming in both liver and brain with the change not being influenced by concurrent melatonin treatment. It is concluded that swimming imposes an oxidative stress on liver and skeletal muscle and the results show that melatonin confers partial protection against oxidative toxicity, especially in muscle.     

心肌肽素对大鼠心肌匀浆脂质过氧化的影响

目的 观察小分子多肽类物质心肌肽素对心肌匀浆孵育脂质过氧化的影响。方法 制备５％（质量体积浓度）大鼠新鲜心肌匀浆液。取１．９ｍｌ均浆液,分别加入０．１ｍｌ生理盐水及不同浓度心肌肽素,使心肌肽素终浓度分别为５,１０,２０μｇ／ｍｌ,置３７℃水浴振荡６０ｍｉｎ。分别以硫代巴比妥酸法和光化学扩增法检测心肌脂质过氧化反应终产物ＭＤＡ的含量及细胞内ＳＯＤ活性。结果 心肌肽素可剂量依赖性地显著降低心肌匀浆中Ｍ     

Protective Effects of d‐Limonene on Lipid Peroxidation and Antioxidant Enzymes in Streptozotocin‐Induced Diabetic Rats

The aim of this study was to evaluate the protective effects of d ‐limonene on the levels of lipid peroxidation by‐products and antioxidant defence systems in the plasma and tissues of normal and streptozotocin (STZ)‐induced diabetes rats. The experimental diabetes was induced in rats by a single dose of STZ (40 mg/kg i.p.) injection, and treatment with d ‐limonene was continued for 45 days. After the treatment period, oxidative stress parameters such as lipid peroxidation by‐products; enzymatic antioxidants such as superoxide dismutase, catalase, glutathione peroxidase and glutathione‐S‐transferase; non‐enzymic antioxidants including reduced glutathione, Vitamins C and E were measured in the plasma and tissues of experimental rats. An increase in the levels of lipid peroxidation by‐products and significant decrease in antioxidant enzymes were observed in untreated diabetic rats. Administration of d ‐limonene to diabetic rats for 45 days caused a significant reduction in the levels of lipid peroxidation by‐products and an increase in the activities of antioxidant enzymes, when compared with the untreated diabetic group. There was no significant difference in normal treated groups, when compared with normal rats. Biochemical observations were substantiated with the help of histopathological examinations through its antioxidant properties and thereby conferred protection against STZ‐induced diabetic rats. The result of this study indicates that d ‐limonene has antioxidant potential in addition to its antidiabetic effect in experimental diabetes.     

Vitamin E Protects Against Lipid Peroxidation Due to Cold-SO2 Coexposure in Mouse Lung

Exposure to sulfur dioxide (SO₂) and cold increases especially in the winter. SO₂ or cold exposure destroys the oxidant/antioxidant balance and increases lipid peroxidation. However, the effect of coexistence of both factors has not been studied yet. Therefore, we investigated the effect of SO₂ and/or repeated short-term cold exposure on the oxidant–antioxidant status and the possible protective role of vitamin E in the cardiopulmonary tissues of mice. Swiss albino mice of both sexes were assigned to eight groups. Four groups were kept at room temperature, injected either with saline or vitamin E (100 mg/kg) in the presence or absence of SO₂ exposure (10 ppm, 1 h/day, 30 days). The remaining four groups received the same protocol but were exposed to cold (4 ± 1°C, 1 h/days, 30 days) instead of room temperature. On day 30, the lung and heart tissues were removed for biochemical analysis. SO₂ and cold coexposure increased lactate level in the lung, and elevated thiobarbituric acid-reactive substance (TBARS) and reduced glutathione levels in both tissues, while vitamin E treatment reversed TBARS increment predominantly in the lung. In conclusion, cold and SO₂ coexposure exerts more deleterious effects in the cardiopulmonary tissues, while vitamin E treatment seems to be protective, particularly in the lung.     

虫草菌丝对肝纤维化小鼠肝脏脂质过氧化的影响

目的:明确虫草菌丝对四氯化碳小鼠肝纤维化的作用及肝脏脂质过氧化的影响.方法:四氯化(碳)皮下注射复制BALB/c小鼠肝纤维化模型,虫草组在造模同时予以虫草菌丝煎剂,直至造模结束.HE染色观察肝组织炎症天狼猩红染色观察肝脏胶原沉积,生化法测定肝组织羟脯氨酸(HyP)、超氧化物歧化酶(SOD)含量,Nothern Blot测定Ⅰ型前(人)原mRNA.结果:与正常小鼠比较,肝纤维化小鼠肝脏肝静脉与汇管区周围肝细胞明显脂肪变性,肝脏胶原沉积,可见纤维(I)隔形成,肝脏Hyp含量及Ⅰ型前胶原基因表达均显著增加,肝脏SOD减少;与模型组比较,虫草组肝脏炎症与胶原沉积减(少)(P＜0.01),Hyp含量及Ⅰ型前胶原mRNA表达明显降低(P＜0.01),SOD活性明显增加(P＜0.01).结论:虫草菌丝制(剂)良好的抗肝纤维化作用,其作用机制可能提高肝脏SOD水平、降低Ⅰ型前胶原mRNA的表达有关.     

一氧化碳对血脂,脂质过氧化物含量及动脉粥样硬化影响的研究

健康雄性SD大鼠吸入62.6、375、750mg/m~3 CO,中、高浓度CO使大鼠血COHb、血清TG、LDL-CH及LPO含量增高,750mg/m~3 CO使主动脉内膜出现内皮下水肿、内皮细胞间裂隙及细胞核扭曲、变形等超微结构改变。提示:脂质过氧化、脂质代谢及主动脉内膜超微结构的改变,是CO所致动脉粥样硬化的重要病因学因素。     

半枝莲总黄酮对红细胞膜脂质过氧化损伤的保护作用

目的:研究半枝莲总黄酮对细胞膜脂质过氧化损伤的影响.方法:以3种自由基生成体系诱导的红细胞膜脂质过氧化为模型,测定半枝莲总黄酮对脂质过氧化的抑制作用.结果:总黄酮对黄嘌呤-黄嘌呤氧化酶系统、H2O2及UV照射3种方法引起的细胞膜脂质过氧化均有抑制作用,其作用呈剂量依赖性,IC50分别为20.59、9.41和19.61lμg·m-1.结论:提示半枝莲总黄酮对自由基引起的细胞膜脂质过氧化损伤有保护作用.     

Lipid Peroxidation and Copper Toxicity in Rats

ABSTRACT

Pentane production was used as an index of lipid peroxidation in male rats fed either 0 or 1000 ppm copper in diets with and without vitamin E. Pentane production by vitamin E-deficient rats not fed copper was greater than that by vitamin E-supplemented rats not fed copper. Pentane production was low by all groups of rats. Copper-fed, vitamin E-deficient and vitamin E-supplemented rats produced more pentane than did respective controls not fed copper. After 9 weeks of feeding the diets, more pentane was produced by vitamin E-deficient than by vitamin E-supplemented rats following intraperitoneal injection of 5 mg of copper/kg of body weight, and vitamin E-deficient rats fed copper produced 5-fold more pentane than did those not fed copper. Thiobarbituric acid-reactants were highest in blood, kidney and liver from copper-fed rats. Lipid-soluble fluorophores in spleen were lowest In vitamin E-supplemented rats not fed copper and highest in copper-fed, vitamin E-deficient rats.     

Inhibitory Effects of Isoflavones in Sophora mooracrotiana on Lipid Peroxidation by Superoxide

The possible inhibitory effects were investigated for three isoflavones: sophoraisoflavone A, and licoisoflavones A and B, isolated from Sophora mooracrotiana Benth ex Baker, on lipid peroxidation by superoxide anion. They inhibited the production of lipid peroxidation each by superoxide anion and the generation of superoxide anion by the xanthinexanthine oxidase system. Their effects were similar to superoxide dismutase as a superoxide anion scavenger. These results demonstrate that these isoflavones have inhibitory effects on oxidative stress.     

Effects of the Long-Term Depletion of Reduced Glutathione in Mice Administered L-Buthionine-S,R-sulfoximine

Effects of the Long-Term Depletion of Reduced Glutathione inMice Administered L-Buthionine-S,R-sulfoximine. SUN, J. D.,RAGSDALE, S. S., BENSON, J. M., AND HENDERSON, R. F. (1985).Fundam. Appl. Toxicol.. 5,913-919. Previous methods to depletein vivo concentrations of reduced glutathione (GSH) have notbeen able to lower tissue GSH levels for extended periods, havebeen toxic, and can alter the metabolism of xenobiotics. A possiblealternative to lower in vivo concentrations of GSH may be theuse of buthionine-S,R-sulfoximine (BSO) in the drinking waterof laboratory animals to inhibit the biosynthesis of GSH. Ithas been previously reported that 20 mM BSO in the drinkingwater given to mice was able to lower GSH levels in a varietyof tissues after 15 days. In order to more fully characterizethe in vivo depletion of GSH in tissues by ingestion of BSOand determine if this method would be suitable in studies requiringdepressed levels of GSH for extended periods, we added differentamounts of this agent to the drinking water given to mice forvarious times up to 28 days. We found that ingested BSO at thehighest concentrtion used in drinking water (30 mM) was ableto maximally lower GSH concentrations in mouse lungs, lung lavagefluid, liver, kidneys, and blood to 59.0 ? 3.6%, 35.0 ? 5.1%,44.3 ? 1.5%, 69.5 ? 3.9%, and 70.0 ? 6.0% of control mice, respectively,for up to 28 days. These lowered concentrations of tissue GSHreturned to control levels after mice were returned to untreateddrinking water for 7 days. The potential toxicity of such treatmentswas also evaluated. Levels of alkaline phosphatase, lactatedehydrogenase, glucose-6-phosphate dehydrogenase, glutathioneperoxidase, and glutathione reductase in lungs and lung lavagefluid, and total and differential cell counts from lung lavagefluid were not different between control and BSO-treated mice.This showed that BSO treatment did not produce indications oflung injury as measured by these biochemical parameters. Serumaspartyl transferase and -glutamyl transpeptidase activitieswere unaffected by the BSO treatments, indicating normal liverfunctions. Lung and liver cytochrome P-450 concentrations werealso not different between controls and BSO-treated animals.Thus, BSO in the drinking water of mice was able to effectivelylower in vivo levels of GSH without eliciting aCUte toxic responses.