Exposure to the fern Onychium contiguum causes increase in lipid peroxidation and alters antioxidant status in urinary bladder

The status of lipid peroxidation, glutathione, glutathione peroxidase, glutathione reductase, glutathione-S-transferase, superoxide dismutase, catalase, ascorbic acid, and alpha-tocopherol was studied in the urinary bladder of guinea pigs exposed to the carcinogenic fern Onychium contiguum. There was significant increase in the preformed lipid peroxides in the urinary bladders from fern exposed animals. The amount of lipid peroxides produced on incubation of urinary bladder homogenates with or without catalyst was significantly higher in the fern exposed animals. The concentrations of glutathione and alpha-tocopherol and the activities of glutathione reductase and catalase were elevated in the urinary bladders of the animals exposed to the fern. No effect was observed on the concentration of ascorbic acid and the activities of glutathione peroxidase, glutathione-S-transferase, and superoxide dismutase. It is summarized that the fern toxins increased oxidative stress in the urinary bladder and antioxidant status was altered. However, the altered antioxidant status did not provide protection from the toxin induced injury. Histopathology of the urinary bladder in the fern exposed animals revealed oedema, haemorrhages, and congestion. This is the first study to show increase in lipid peroxidation along with altered antioxidant status in the urinary bladder of fern exposed animals.     

Lipid peroxidation and benzo[a]pyrene activation to mutagenic metabolites: in vivo influence of vitamins A, E and C and glutathione in both dietary vitamin A sufficiency and deficiency

Rats fed with either a sufficient-vitamin A or a vitamin A-free diet were pretreated with 750 mg/kg body weight of retinyl palmitate, alpha-tocopherol acetate, ascorbic acid or glutathione. Benzo[a]pyrene (BaP) metabolism and BaP-induced mutagenesis in Salmonella typhimurium TA98 were investigated and related to lipid peroxidation activities in postmitochondrial (S9) liver fraction. The microsomal mixed-function oxidase activities were decreased by vitamin A deficiency and weakly affected by scavenger treatment. The rate of lipid peroxidation of microsomal membranes was unaffected by vitamin A deficiency because of decreased polyunsaturated fatty acids and increased vitamin E contents. However, lipid peroxidation was decreased by pretreatment with fat-soluble vitamins (chiefly vitamin E) and increased by ascorbic acid. Within each experimental group both BaP metabolism and BaP mutagenic activity were closely correlated with the rate of lipid peroxidation. In vitamin A deficiency, the increased BaP metabolism and mutagenicity could be related to a decrease in cytosolic contents of scavengers (vitamin A and glutathione). In Ames test conditions, the free radical pathway became a route for BaP metabolism and thus the BaP activation to mutagenic metabolites is related to the cellular status in free radical scavengers.     

Ascorbic acid and alpha-tocopherol as potent modulators on arsenic induced toxicity in mitochondria

Arsenic exists ubiquitously in our environment and various forms of arsenic circulate in air, water, soil and living organisms. Since arsenic compounds have shown to exert their toxicity chiefly by generating reactive oxygen species, we have evaluated the effect of antioxidants ascorbic acid and alpha-tocopherol on lipid peroxidation, antioxidants and mitochondrial enzymes in liver and kidney of arsenic exposed rats. A significant increase in the level of lipid peroxidation and decrease in the levels of antioxidants and in the activities of mitochondrial enzymes were observed in arsenic intoxicated rats. Co-administration of arsenic treated rats with ascorbic acid and alpha-tocopherol showed significant reduction in the level of lipid peroxidation and elevation in the levels of ascorbic acid, alpha-tocopherol, glutathione and total sulfhydryls and in the activities of isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, NADH-dehydrogenase and cytochrome c oxidase. From our results, we conclude that ascorbic acid and alpha-tocopherol alleviate arsenic- induced alterations in mitochondria.     

Protective effect of green tea against lipid peroxidation in the rat liver, blood serum and the brain

This paper reports data on the effect of green tea on the lipid peroxidation products formation and parameters of antioxidative system of the liver, blood serum and central nervous tissue of healthy young rats drinking green tea for five weeks. The rats were permitted free access to solubilized extract of green tea. Bioactive ingredients of green tea extract caused in the liver an increase in the activity of glutathione peroxidase and glutathione reductase and in the content of reduced glutathione as well as marked decrease in lipid hydroperoxides (LOOH), 4-hydroksynonenal (4-HNE) and malondialdehyde (MDA). The concentration of vitamin A increased by about 40%. Minor changes in the measured parameters were observed in the blood serum. GSH content increased slightly, whereas the index of the total antioxidant status increased significantly. In contrast, the lipid peroxidation products, particularly MDA was significantly diminished. In the central nervous tissue the activity of superoxide dismutase and glutathione peroxidase decreased while the activity od glutathione reductase and catalase increased after drinking green tea. Moreover the level of LOOH, 4-HNE and MDA significantly decreased. The use of green tea extract appeared to be beneficial to rats in reducing lipid peroxidation products. These results support and substantiate traditional consumption of green tea as protection against lipid peroxidation in the liver, blood serum, and central nervous tissue.     

Short-term ascorbic acid deficiency induced oxidative stress in the retinas of young guinea pigs

We examined whether short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs. Four-week-old guinea pigs were given a scorbutic diet (20 g/animal/day) with and without adequate ascorbic acid (400 mg/animal/day) in drinking water for 3 weeks. The serum concentrations of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 14.1 and 4.1%, respectively, of those in the adequate group. The retinal contents of the reduced form of ascorbic acid and the oxidized form of ascorbic acid in the deficient group were 6.4 and 27.3%, respectively, of those in the adequate group. The retinal content of thiobarbituric acid-reactive substances, an index of lipid peroxidation, was 1.9-fold higher in the deficient group than in the adequate group. Retinal reduced glutathione and vitamin E contents in the deficient group were 70.1 and 69.4%, respectively, of those in the adequate group. This ascorbic acid deficiency did not affect serum thiobarbituric acid-reactive substances and reduced glutathione concentrations but increased serum vitamin E concentration. These results indicate that short-term ascorbic acid deficiency induces oxidative stress in the retinas of young guinea pigs without disrupting systemic antioxidant status.     

Hypolipidemic and antioxidant effects of curcumin and capsaicin in high-fat-fed rats

The beneficial hypolipidemic and antioxidant influences of the dietary spice compounds curcumin and capsaicin were evaluated. Curcumin, capsaicin, or their combination were included in the diet of high-(30%)-fat-fed rats for 8 weeks. Dietary high-fat-induced hypertriglyceridemia was countered by dietary curcumin, capsaicin, or their combination by 12%-20%. Curcumin, capsaicin, and their combination also produced a slight decrease in serum total cholesterol in these animals. Serum alpha-tocopherol content was increased by dietary curcumin, capsaicin, and their combination in high-fat-fed rats. Serum total thiol content in high-fat-fed animals and serum ascorbic acid in normal animals was elevated by the combination of curcumin and capsaicin. Hepatic glutathione was increased by curcumin, capsaicin, or their combination in normal animals. Hepatic glutathione and alpha-tocopherol were increased, whereas lipid peroxide level was reduced by dietary curcumin and combination of curcumin and capsaicin in high-fat-fed animals. Serum glutathione peroxidase and glutathione transferase in high-fat-fed rats were generally higher as a result of dietary curcumin, capsaicin, and the combination of curcumin and capsaicin. Hepatic glutathione reductase and glutathione peroxidase were significantly elevated by dietary spice principles in high-fat-fed animals. The additive effect of the 2 bioactive compounds was generally not evident with respect to hypolipidemic or antioxidant potential. However, the effectiveness of the combination was higher in a few instances.     

Antioxidant protection of phospholipid bilayers by alpha-tocopherol. Control of alpha-tocopherol status and lipid peroxidation by ascorbic acid and glutathione

Factors affecting the balance between pro- and antioxidant effects of ascorbic acid and glutathione were studied in soybean phosphatidylcholine liposomes challenged with Fe2+/H2O2. Effective antioxidant protection by alpha-tocopherol appeared to be due to efficient reaction with lipid oxy-radicals in the bilayer rather than to interception of initiating oxygen radicals. At concentrations above a threshold level of approximately 0.2 mol % (based on phospholipid content), alpha-tocopherol completely suppressed lipid oxy-radical propagation, which was measured as malondialdehyde production. Both ascorbic acid and glutathione, alone or in combination, enhanced lipid oxy-radical propagation. Alpha-Tocopherol, incorporated into liposomes at concentrations above its threshold protective level, reversed the pro-oxidant effects of 0.1-1.0 mM ascorbic acid but not those of glutathione. Ascorbic acid also prevented alpha-tocopherol depletion. The combination of ascorbic acid and subthreshold levels of alpha-tocopherol only temporarily suppressed lipid oxy-radical propagation and did not maintain the alpha-tocopherol level. Glutathione antagonized the antioxidant action of the alpha-tocopherol/ascorbic acid combination regardless of alpha-tocopherol concentration. These observations indicate that membrane alpha-tocopherol status can control the balance between pro- and antioxidant effects of ascorbic acid. The data also provide the most direct evidence to date that ascorbic acid interacts directly with components of the phospholipid bilayer.     

Lipid-mobilizing effect of reduced glutathione and its intensifying action on lecithin-cholesterol acyltransferase activity in blood serum of rats

Effect of reduced glutathione (50 mg/100 g) on lipid distribution between organs (liver and kidney) and lecithin-cholesterol acyltransferase (LCAT) activity in blood serum of rats was investigated. The accumulation of common lipids as a result of speeding up the absorbtion of blood serum unsaturated fatty acids and relative decrease of lipids unsaturation in the liver and lipid content dynamics in kidneys owing to the intensification of two processes in this organ: the transport of polyene fatty acids in composition of blood serum lipoprotein lipids to kidney cells and peroxidation of membrane phospholipids were found out. The activating effect of GSH (in vivo and in vitro) on LCAT activity of rat blood serum was shown. It was summarised that GSH-intensification of blood serum etherification ability may be a basic component of reduced glutathione lipid mobilization effect.     

Selenium deficiency-induced alterations in the vascular system of the rat

To enunciate the mechanisms whereby Se protects against cardiovascular diseases, weanling male Wistar rats were fed deficient (0.022 mg/kg diet) and adequate (0.159 mg/kg diet) Se diets for 14 and/or 39 wk. As the Se content and glutathione peroxidase activity were decreased and the lipid peroxide level was increased, the plasma 6-keto-PGF_1α concentration of the Se-deficient group was markedly decreased in blood and tissues of the Se-deficient rats, as compared with the Se-adequate animals. Furthermore, the Se-deficient group had significantly lower plasma nitric oxide content and vascular nitric oxide synthase activity, higher erythrocyte sedimentation equation K value and aggregation index, and lower erythrocyte deformability than the Se-adequate group. Experimental Se deficiency also resulted in significant increases in serum total cholesterol and low-density lipoprotein cholesterol levels and a significant decrease in serum high-density lipoprotein cholesterol level. These results give some experimental supports to the hypothesis that low Se status and lipid peroxidation are involved in the etiology of cardiovascular diseases.     

Modulation of cyclophosphamide-induced early lung injury by curcumin,an anti-inflammatory antioxidant

Cyclophosphamide causes lung injury in rats through its ability to generate free radicals with subsequent endothelial and epithelial cell damage. In order to observe the protective effects of a potent anti-inflammatory antioxidant, curcumin (diferuloyl methane) on cyclophosphamide-induced early lung injury, healthy pathogen free male Wistar rats were exposed to 20 mg/100 g body weight of cyclophosphamide, intraperitoneally as a single injection. Prior to cyclophosphamide intoxication oral administration of curcumin was performed daily for 7 days. At various time intervals (2, 3, 5 and 7 days post insult) serum and lung samples were analyzed for angiotensin converting enzyme, lipid peroxidation, reduced glutathione and ascorbic acid. Bronchoalveolar lavage fluid was analyzed for biochemical constituents. The lavage cells were examined for lipid peroxidation and glutathione content. Excised lungs were analyzed for antioxidant enzyme levels. Biochemical analyses revealed time course increases in lavage fluid total protein, albumin, angiotensin converting enzyme (ACE), lactate dehydrogenase, N-acetyl--D-glucosaminidase, alkaline phosphatase, acid phosphatase, lipid peroxide levels and decreased levels of glutathione (GSH) and ascorbic acid 2, 3, 5 and 7 days after cyclophosphamide intoxication. Increased levels of lipid peroxidation and decreased levels of glutathione and ascorbic acid were seen in serum, lung tissue and lavage cells of cyclophosphamide groups. Serum angiotensin converting enzyme activity increased which coincided with the decrease in lung tissue levels. Activities of antioxidant enzymes were reduced with time in the lungs of cyclophosphamide groups. However, a significant reduction in lavage fluid biochemical constituents, lipid peroxidation products in serum, lung and lavage cells with concomitant increase in antioxidant defense mechanisms occurred in curcumin fed cyclophosphamide rats. Therefore, our results suggest that curcumin is effective in moderating the cyclophosphamide induced early lung injury and the oxidant-antioxidant imbalance was partly abolished by restoring the glutathione (GSH) with decreased levels of lipid peroxidation.     

Influence of 6-week exercise training on erythrocyte and liver antioxidant defense in hyperinsulinemic rats

High dosage of fructose in rats causes insulin resistance and hyperinsulinemia. This study investigates the effect of physical exercise on oxidant-antioxidant balance in rats fed a high fructose diet, which show characteristic features of insulin resistance. Products of lipid peroxidation and the activity of enzymic antioxidants namely superoxide dismutase, catalase, glutathione peroxidase, glutathione-S-transferase and glutathione reductase, in red blood cells (RBCs) and liver were assayed. Levels of non-enzymic antioxidants alpha-tocopherol and ascorbic acid and of protein and non-protein thiols were also determined. The levels of lipid peroxides, diene conjugates, lipofuscin and hydroperoxides were significantly higher in the liver of fructose-fed rats. The RBCs showed significantly higher susceptibility to H(2)O(2)-induced stress compared to control rats. Inadequate antioxidant system was noted in high fructose-fed rats. Physical training to these rats reversed the adverse effects, which could be important in alleviating the pathological consequences of insulin resistance.     

Protective effect of modified glucomannans and organic selenium against antioxidant depletion in the chicken liver due to T-2 toxin-contaminated feed consumption

The aim of this work was to assess the effect of T-2 toxin on the antioxidant status of the chicken and to study possible protective effects of modified glucomannan (Mycosorb) and organic selenium (Sel-Plex). Inclusion of T-2 toxin in the chickens' diet (8.1 mg/kg for 21 days) was associated with significant decreases in the concentrations of selenium (Se)(by 32.2%), alpha-tocopherol (by 41.4%), total carotenoids (by 56.5%), ascorbic acid (by 43.5%) and reduced glutathione (by 56.3%) in the liver, as well as a decrease in the hepatic activity of Se-dependent glutathione peroxidase (Se-GSH-Px) (by 36.8%). However, inclusion of modified glucomannans into the T-2 toxin-contaminated diet provided a partial protection against the detrimental effects of the mycotoxin on the antioxidant defences in the chicken liver. For example, the Se concentration in the liver was restored completely, although the Se-GSH-Px activity in the liver increased to only 81% of its control value. These protective effects of modified glucomannas were associated with a 45% reduction of lipid peroxidation in the liver in comparison to the effects of T-2 toxin alone. A combination of modified glucomannas with organic Se was shown to provide further protection against toxin-induced antioxidant depletion and lipid peroxidation in the chicken liver. Thus, the data clearly indicate a major protective effect of the mycotoxin-binder in combination with organic Se against the detrimental consequences of T-2 toxin-contaminated feed consumption by growing chickens.     

Taurine restores ethanol-induced depletion of antioxidants and attenuates oxidative stress in rat tissues

Summary. Ethanol by its property of generating free radicals during the course of its metabolism causes damage to cell structure and function. The study investigates the protective effects of the antioxidant aminoacid taurine on ethanol-induced lipid peroxidation and antioxidant status. Male Wistar rats of body weight 170–190g were divided into 4 groups and maintained for 28 days as follows: a control group and taurine-supplemented control group, taurine supplemented and unsupplemented ethanol-fed group. Ethanol was administered to rats at a dosage of 3g/kg body weight twice daily and taurine was provided in the diet (10g/kg diet). Lipid peroxidation products and antioxidant potential were quantitated in plasma and in following tissues liver, brain, kidney and heart.Increased levels of thiobarbituric acid substances (TBARS) and lipid hydroperoxides (LHP) in plasma and tissues, decreased activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were observed in hemolysate and tissues of ethanol-fed rats. The contents of reduced glutathione (GSH), -tocopherol and ascorbic acid in plasma and tissues were significantly reduced in these animals as compared to control animals. Simultaneous administration of taurine along with ethanol attenuated the lipid peroxidation process and restored the levels of enzymatic and non-enzymatic antioxidants. We propose that taurine may have a bioprotective effect on ethanol-induced oxidative stress.     

Age-related changes of lipid spectrum, level of lipid peroxidation, and antioxidant defence in the liver and blood of rats

It has been shown that the lowest level of total lipids, cholesterol, triacylglycerols and products of lipid peroxidation of blood and liver, as a rule, is specific to adult rats. These characteristics are significantly higher for old and young animals. At the same time, the level of glutathione and alphatocopherols in adults' liver is much higher than in young and old rats. It suggests the lower level of processes of lipid peroxidation in adult mature rats. The relative high level of products of lipid peroxidation and low content of alpha-tocopherols in old rats' liver (against the background of higher activity and glutamineperoxidase, and glutathionereductase than in adults) suggests tocopherol deficiency in old animals. High content of total lipids, cholesterol and cholesterol entering into the composition of lipoprotein of different density, triacylglycerols, diene conjugates and malonic dialdehide, activity of glutathione-dependent enzymes of antioxidant defence in young animals as compared with these levels in adult rats seems to be associated with agerelated hypercholesterolemia and intensive plastic changes of a growing organism.     

Antioxidant system activation in rats with experimental cirrhosis after injection of cryopreserved fetal liver cells

The possibility to recover the antioxidant system in rats with experimental liver cirrhosis (LC) after allo- and xenotransplantation of cryopreserved fetal liver cells (FLC) was investigated. It was shown that the content of lipid peroxidation products in the blood serum of animals with LC four weeks after FLC transplantation decreased significantly as compared to control group. Such changes were accompanied by a significant increase of catalase (CAT), glutathione reductase (GR), Se-dependent glutathione peroxidase (GP) activity in the liver and total anti-oxidative activity (AOA) of blood. Obtained results demonstrate that the main direction of FLC effects in animals with LC agree with that we observed previously in other experimental models (partial hepatectomy, chronic alcohol poisoning and hypercholesterolemia). In conclusion, cell therapy may be considered as the universal method for correction of disorders in regulation of free-radical processes in various experimental pathologies.     

Interaction of nitrogen dioxide with human plasma. Antioxidant depletion and oxidative damage.

Nitrogen dioxide (NO2.) is often present in inhaled air and may be generated in vivo from nitric oxide. Exposure of human blood plasma to NO2. caused rapid losses of ascorbic acid, uric acid and protein thiol groups, as well as lipid peroxidation and depletions of alpha-tocopherol, bilirubin and ubiquinol-10. No increase in protein carbonyls was detected. Supplementation of plasma with ascorbate decreased the rates of lipid peroxidation, alpha-tocopherol depletion and loss of uric acid. Uric acid supplementation decreased rates of lipid peroxidation but not the loss of alpha-tocopherol. We conclude that ascorbic acid, protein -SH groups, uric acid and alpha-tocopherol may be important agents protecting against NO2. in vivo. If these antioxidants are depleted, peroxidation of lipids occurs and might contribute to the toxicity of NO2..     

Alpha-tocopherol protection of erythrocytes from hemolysis induced by thermal injury

It is shown that skin burn is accompanied by activation of lipid peroxidation (accumulation of TBA-reactive substances and of fluorescent end-products) in the blood of experimental animals. The decrease in red blood cell membrane stability was demonstrated exerting as increase in the rate of spontaneous hemolysis, content of extraerythrocyte++ haemoglobin and increased sensitivity to exogenous oleic acid. It is estimated that alpha-tocopherol possesses protective stabilizing effect on red blood cell membrane. This stabilizing action is observed when alpha-tocopherol was injected both before the skin burn and immediately after it. It is concluded that two different mechanisms are responsible for stabilizing effect of tocopherol, namely: 1) antiradical, realized via inhibition of lipid peroxidation, and 2) non-antioxidant, caused by interaction of tocopherol with phospholipid hydrolysis products by phospholipases A2 (free fatty acids and lysophospholipids).     

Effect of oral methionine and vitamin E on blood lipid peroxidation in vitamin B6 deficient rats

Lipid peroxidation in blood of vitamin B6 deficient rats was significantly increased when compared to pair-fed controls. The observed increased lipid peroxidation in vitamin B6 deficiency was correlated with high levels of lipids, metal ions and low levels of antioxidants, alpha-tocopherol, ascorbic acid and reduced GSH. Supplementation of methionine or vitamin E along with the vitamin B6 deficient diet restored the levels of antioxidants to near normal and also protected against oxidative stress. However plasma TBARS level as well as total lipids were still elevated in M-B6 diet fed rats and normalized in E-B6-d rats.     

Effect of beta-carotene and carotene producing yeast Phaffia rhodozyma on oxidative stress in rats treated with tetrachloromethane

Supplementation of rats' diet with beta-carotene or biomass of carotene producing yeast Phaffia rhodozyma caused a decrease of aminotransferases in the blood serum as well as a decrease of lipid peroxidation products and protein carbonil groups in the liver, brain and myocardium tissues of animals treated with tetrachloromethane. When compared to the control group the activity of superoxide dismutase, catalase and glutathione peroxidase in the liver of carotene fed rats were respectively 1.6, 2.2, and 1.5-fold higher. Thus, these supplements to standard diet slow down development of tetrachlorometane mediated oxidative stress in rats.     

Protective effect of ursolic acid on ethanol-mediated experimental liver damage in rats

Ursolic acid is a triterpenoid that exists in nature and is the major component of some traditional medicinal herbs. In this study, ursolic acid has been evaluated for its hepatoprotective effect against chronic ethanol-mediated toxicity in rats. Ethanol administration (7.9 g/kg/day) for 60 days resulted in increased oxidative stress, decreased antioxidant defense and liver injury. It also negatively affected the serum total protein, albumin and A/G ratio. Subsequent to the experimental induction of toxicity (i.e. after the initial period of 30 days) ursolic acid treatment performed by co-administering ursolic acid (10, 20 and 40 mg/kg body weight) for 30 days along with the daily dose of ethanol. While this treatment causing a significant improvement in body weight, food intake and serum protein levels, it decreases serum aminotransferase activities (aspartate aminotransferase and alanine aminotransferase) and total bilirubin levels. Ursolic acid improved the antioxidant status of alcoholic rats, which is evaluated by the decreased levels of lipid peroxidation markers in plasma (thiobarbituric acid reactive substances and lipid hydroperoxides) and increased levels of circulatory antioxidants such as reduced glutathione, ascorbic acid and alpha-tocopherol. Histopathological observations were also in correlation with the biochemical parameters. The activity of ursolic acid (20 mg/kg) compares well with silymarin, a known hepatoprotective drug, and seems to be better in certain parameters. The protective effect of ursolic acid is probably related to its antioxidant activities.