Mitogenic and Mutagenic Effects of Ionized Air on <Emphasis Type="Italic">Allium fistulosum</Emphasis> L.

In the apical meristem of Allium fistulosum, the relationship between peroxide lipid oxidation, antioxidant activity, proliferative processes, the yield of chromosomal aberrations and duration the exposure to ionized air was studied. Under the influence of air oxygen ions, superoxide dismutase and catalase activities increased, proliferative processes were stimulated, and shifts occurred in the process of lipid peroxidation in cells of A. fistulosum. When these cells were treated with air oxygen for 40 min, hydrogen peroxide and iron sulfate (II) enhanced oxygen biostimulating effect via stimulation of antioxidant enzyme activity and inhibition of lipid peroxidation. Under these conditions, cell proliferation was intensified and the yield of chromosomal aberrations was reduced in A. fistulosum rootlets. When the time of seed treatment with ionized air was increased to 80 min, lipid peroxidation was activated, antioxidant enzyme activity was inhibited, and the yield of chromosomal aberration increased in seedlings. It was concluded that the biostimulating activity of ionized air was mediated by active oxygen species generated in the cell. The accumulation of TBA(thiobarbituric acid)-reactive products was shown to be related to a decrease in antioxidant enzyme activity and an increase in the yield of chromosomal aberrations. It is emphasized that the mutagenic effect of ionized air is associated with generating conditions that support Fenton reaction and OH-radical formation in the cell.     

Effects by doxorubicin on the myocardium are mediated by oxygen free radicals

We hypothesized that doxorubicin (DOX) induces cardiotoxicity of myocardium via oxygen radicals. The present study is aimed at examining the membrane alterations by oxygen radicals generated by DOX in adult rats and cultured neonatal myocytes. Our results showed that DOX 1) decreased beta-adrenoceptor (BAR) density in the cell membrane, 2) increased the membrane permeability of cultured neonatal rat myocytes and 3) altered the ultrastructure of myofibrils and subplasmalemmal actin networks. These effects were reproducible by exogenous hydrogen peroxide. The antioxidant melatonin (MLT) inhibited enzyme leakage and peroxidation in a concentration-dependent manner. It is concluded that DOX induces cardiotoxicity through lipid peroxidation and melatonin is an effective antioxidant against the reactive oxygen intermediates generated by DOX.     

Effect of oral methionine on blood lipid peroxidation and antioxidants in alloxan-induced diabetic rats

Supplementation of thiol compounds has been suggested to protect against the toxic effects of reduced oxygen species by contributing to the thiol pool of the cell. The present study was designed to determine whether supplementation of methionine in the diet of diabetic animals protected against the oxidative stress in diabetic pathology. Oral methionine was administered at a dosage of 330 mg/100 g feed to diabetic rats. The effect was compared with the effect of insulin administration. Levels of lipid peroxides were measured in plasma, erythrocytes, and erythrocyte membrane. Anti-oxidants were measured in plasma. Diabetic condition was associated with increased lipid peroxidation and depletion in antioxidant levels. Although methionine did not affect the level of blood glucose and some of the antioxidants, it lowered the lipid peroxide content in blood. Erythrocyte lipid peroxidation activity was unaffected by methionine treatment. Administration of insulin lowered both plasma and erythrocyte lipid peroxide levels.     

Human selenium-containing single-chain variable fragment with glutathione peroxidase activity protects NIH3T3 fibroblast against oxidative damage

Ultraviolet B (UVB medium wave, 280–315 nm) induces cellular oxidative damage and apoptosis by producing reactive oxygen species (ROS). Glutathione peroxidase functions as an antioxidant by catalyzing the reduction of hydrogen peroxide, the more important member of reactive oxygen species. A human selenium-containing single-chain variable fragment (se-scFv-B3) with glutathione peroxidase activity of 1288 U/μmol was generated and investigated for its antioxidant effects in UVB-induced oxidative damage model. In particular, cell viability, lipid peroxidation extent, cell apoptosis, the change of mitochondrial membrane potential, caspase-3 activity and the levels of intracellular reactive oxygen species were assayed. Human se-scFv-B3 protects NIH3T3 cells against ultraviolet B-induced oxidative damage and subsequent apoptosis by prevention of lipid peroxidation, inhibition of the collapse of mitochondrial membrane potential as well as the suppression of the caspase-3 activity and the level of intracellular ROS. It seems that antioxidant effects of human se-scFv-B3 are mainly associated with its capability to scavenge reactive oxygen species, which is similar to that of the natural glutathione peroxidase.     

Lipid peroxidation induced by DHA enrichment modifies paracellular permeability in Caco-2 cells: protective role of taurine

Dietary enrichment with docosahexaenoic acid (DHA) has numerous beneficial effects on health. However, the intake of high doses of polyunsaturated fatty acids can promote lipid peroxidation and the subsequent propagation of oxygen radicals. The purpose of this study was to evaluate the effect of DHA on lipid peroxidation and tight junction structure and permeability in Caco-2 cell cultures. Moreover, the effects of taurine, a functional ingredient with antioxidant properties, were also tested. Differentiated Caco-2 cell monolayers were maintained in DHA-supplemented conditions with or without added taurine. Incubation with 100 microM DHA increased lipid peroxidation and paracellular permeability, in parallel with a redistribution of the tight junction proteins occludin and ZO-1. Taurine partially prevented all of these effects. The participation of reactive oxygen and nitrogen species in increased paracellular permeability was also examined using various agents that modify the formation of superoxide radical, hydrogen peroxide, nitric oxide, and peroxynitrite. We conclude that hydrogen peroxide and peroxynitrite may be involved in the DHA-induced increase in paracellular permeability and that the protective role of taurine may be in part related to its capacity to counteract the effects of hydrogen peroxide.     

Participation of active oxygen species in the induction of chromosomal aberrations by cadmium chloride in cultured Chinese hamster cells

The effect of various scavengers of active oxygen species on the induction of chromosomal aberrations by cadmium chloride (CdCl2) was investigated in cultured Chinese hamster V79 cells. Incidences of chromosomal aberrations by CdCl2 were partially or fully reduced by the presence of catalase, mannitol (a scavenger of hydroxyl radicals) and butylated hydroxytoluene (BHT, an antioxidant). These findings may indicate participation of the active oxygen species such as hydrogen peroxide (H2O2) or hydroxyl radicals in the clastogenicity of cadmium. In contrast, superoxide dismutase (SOD) and dimethylfuran (a scavenger of singlet oxygen) did not influence incidences of chromosomal aberrations by CdCl2. These results suggest that superoxide anion and singlet oxygen are not directly involved in the clastogenicity of the metal. The presence of aminotriazole (an inhibitor of catalase) increased incidences of chromosomal aberrations by CdCl2. This emphasizes participation of H2O2 in the clastogenicity of cadmium.     

Antioxidative defense system in pigeonpea roots under waterlogging stress

Pigeonpea [Cajanus cajan (L.) Millsp.] is a waterlogging-sensitive legume crop. We studied the effect of waterlogging stress on hydrogen peroxide (H₂O₂) content, lipid peroxidation and antioxidant enzyme activities in two pigeonpea genotypes viz., ICPL-84023 (waterlogging resistant) and MAL-18 (waterlogging susceptible). In a pot experiment, waterlogging stress was imposed for 6 days at early vegetative stage (20 days after sowing). Waterlogging treatment significantly increased hydrogen peroxide accumulation and lipid peroxidation, which indicated the extent of oxidative injury posed by stress conditions. Enzyme activities of peroxidase (POX), catalase (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD) and polyphenol oxidase (PPO) increased in pigeonpea roots as a consequence of waterlogged conditions, and all the enzyme activities were significantly higher in waterlogged ICPL-84023 than in MAL-18. POX activity was the maximum immediately after imposing stress, therefore, it was suggested to be involved in early scavenging of H₂O₂, while rest of the enzymes (CAT, APX, SOD and PPO) were more important in late responses to waterlogging. Present study revealed that H₂O₂ content is directly related to lipid peroxidation leading to oxidative damage during waterlogging in pigeonpea. Higher antioxidant potential in ICPL-84023 as evidenced by enhanced POX, CAT, APX, SOD and PPO activities increased capacity for reactive oxygen species (ROS) scavenging and indicated relationship between waterlogging resistance and antioxidant defense system in pigeonpea.     

alpha-Pinene inhibits growth and induces oxidative stress in roots

BACKGROUND AND AIMS: Determining the mode of action of allelochemicals is one of the challenging aspects in allelopathic studies. Recently, allelochemicals have been proposed to cause oxidative stress in target tissue and induce an antioxidant mechanism. alpha-Pinene, one of the common monoterpenoids emitted from several aromatic plants including forest trees, is known for its growth-inhibitory activity. However, its mechanism of action remains unexplored. The aim of the present study was to determine the inhibitory effect of alpha-pinene on root growth and generation of reactive oxygen species, as indicators of oxidative stress and changes in activities of antioxidant enzymes. METHODS: Effects of alpha-pinene on early root growth were studied in five test species, Cassia occidentalis, Amaranthus viridis, Triticum aestivum, Pisum sativum and Cicer arietinum. Electrolyte leakage, lipid peroxidation, hydrogen peroxide generation, proline accumulation, and activities of the enzymes superoxide dismutase (SOD), ascorbate peroxidase (APX), guaiacol peroxidase (GPX), catalase (CAT) and glutathione reductase (GR) were studied in roots of C. occidentalis. KEY RESULTS: alpha-Pinene inhibited the radicle growth of all the test species. Exposure of C. occidentalis roots to alpha-pinene enhanced solute leakage, and increased levels of malondialdehyde, proline and hydrogen peroxide, indicating lipid peroxidation and induction of oxidative stress. Activities of the antioxidant enzymes SOD, CAT, GPX, APX and GR were significantly elevated, thereby indicating the enhanced generation of reactive oxygen species (ROS) upon alpha-pinene exposure. Increased levels of scavenging enzymes indicates their induction as a secondary defence mechanism in response to alpha-pinene. CONCLUSIONS: It is concluded that alpha-pinene inhibits early root growth and causes oxidative damage in root tissue through enhanced generation of ROS, as indicated by increased lipid peroxidation, disruption of membrane integrity and elevated antioxidant enzyme levels.     

Stimulation of thiamine diphosphatase activity by ascorbic acid in rat brain microsomes.

The effect of ascorbic acid on microsomal thiamine diphosphatase activity in rat brain was examined. Ascorbic acid at 0.02--0.1 mM increased the thiamine diphosphatase activity by 20--600% and produced a significant amount of lipid peroxide, which was measured with thiobarbiturate under the same conditions as the enzyme. A lag period of about 10 min was observed in the process of stimulation of enzyme activity by ascorbic acid. The stimulation of enzyme activity and the lipid peroxidation induced by ascorbic acid were blocked by metal-binding compounds (EDTA, alpha,alpha'-dipyridyl, o-phenanthroline) and an antioxidant (N,N'-diphenyl p-phenylenediamine). GSH significantly enhanced the stimulation of enzyme activity and formation of lipid peroxide by 0.02--0.05 mM ascorbic acid. The effect of GSH was due in part to maintenance of the concentration of ascorbic acid in the medium, since GSH could convert dehydroascorbic acid, an oxidized form of ascorbic acid, to ascorbic acid.     

Effects of various oxygen concentrations on antioxidant enzymes and the quantity of tissue phospholipid fatty acids in the carp

Analyses were made of the phsopholipid fatty acids and the antioxidant enzymes in the carp (Cyprinus carpio morpha) at three different oxygen concentrations, corresponding to hyperoxia, hypoxia and anoxia. Variations of the oxygen concentration were found to influence the quantities of phsopholipid fatty acids, as well as the antioxidant enzyme activities. In hyperoxia and hypoxia the amount of polyunsaturated fatty acids in carp liver was higher than in anoxia, but in other tissues there was no significant differences. As to the antioxidant enzyme system, the glutathione peroxidase activity and the lipid peroxidation value increased significantly with decrease of the oxygen concentration, while the total superoxide dismutase activity decreased on lowering of the oxygen level.     

Persistent oxidative stress after ionizing radiation is involved in inherited radiosensitivity

The SW620IR1 cell line was derived from SW620 human colon cells surviving to ionizing radiations. It shows an increased radiosensitivity and a higher yield of spontaneous chromosomal aberrations. In order to check whether altered reactive oxygen intermediates (ROI) metabolism is involved in this inherited phenotype, we compared the two cell lines for their radiation-induced modifications at the level of ROI production, antioxidant activities, and chromosomal aberrations. Compared to SW620, SW620IR1 cells exhibit a higher and more persistent ROI induction after various doses of ionizing radiations and a higher yield of dicentric chromosomes. They are also characterized by lower basal activities of glutathione peroxidase and manganese-containing superoxide dismutase, and lower ability to induce these antioxidant defenses after irradiation. Resumption of cell growth after irradiation coincides with maximal induction of antioxidant activities and normalization of ROI concentration. However, at that time radiation-induced chromosomal aberrations are not completely eliminated, leading to the proliferation of genetically unstable cells. These results indicate that the inherited sensitivity of SW620IR1 cells is associated with altered antioxidant activities resulting in higher and more prolonged oxidative stress after radiation exposure. They also suggest that the normalization of ROI levels allows these p53 mutant cells to resume proliferation although high levels of DNA damages are still persisting, thereby explaining the chromosomal instability observed as a delayed effect of radiation exposure.     

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.     

Elevated semicarbazide-sensitive amine oxidase (SSAO) activity in lung with ischemia-reperfusion injury: protective effect of ischemic preconditioning plus SSAO inhibition

Ischemic preconditioning (IP) has been shown to protect the lung against ischemia-reperfusion (I/R) injury. Although the production of reactive oxygen species (ROS) has been postulated to play a crucial role in I/R injury, the sources of these radicals in I/R and the mechanisms of protection in IP remain unknown. Since it was postulated that deamination of endogenous and exogenous amines by semicarbazide-sensitive amine oxidase (SSAO) in tissue damage leads to the overproduction of hydrogen peroxide (H2O2), we investigated the possible contribution of tissue SSAO to excess ROS generation and lipid peroxidation during I/R and IP of the lung. Male Wistar rats were randomized into 6 groups: control lungs were subjected to 30 min of perfusion in absence and presence of SSAO inhibitor, whereas the lungs of the I/R group were subjected to 2 h of cold ischemia following the 30 min of perfusion in absence and presence of SSAO inhibitor. IP was performed by two cycles of 5 min ischemia followed by 5 min of reperfusion prior to 2 h of hypothermic ischemia in absence and presence of SSAO inhibitor. Lipid peroxidation, reduced (GSH) and oxidized (GSSG) glutathione levels, antioxidant enzyme activities, SSAO activity, and H2O2 release were determined in tissue samples of the study groups. Lipid peroxidation, glutathione disulfide (GSSG) content, SSAO activity and H2O2 release were increased in the I/R group, whereas GSH content, GSH/GSSG ratio and antioxidant enzyme activities were decreased. SSAO activity, H2O2 release, GSSG content and lipid peroxidation were markedly decreased in the IP group, whereas GSH content, GSH/GSSG ratio and antioxidant enzyme activities were significantly increased. SSAO activity was found to be positively correlated with H2O2 production in all study groups. Increased lipid peroxidation, SSAO activity, GSSG and H2O2 contents as well as decreased GSH and antioxidant enzyme levels in I/R returned to their basal levels when IP and SSAO inhibition were applied together. The present study suggests that application of IP and SSAO inhibition together may be more effective than IP alone against I/R injury in the lung.     

Age-dependent variations in mitochondrial and cytosolic antioxidant enzymes and lipid peroxidation in different regions of central nervous system of guinea pigs

The age-related changes in the activities of antioxidant enzymes of mitochondrial and cytosolic fractions were measured in different regions of the central nervous system (CNS) in 10 and 32 months old guinea pigs. In old animals, the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) were reduced (p < 0.05) in all the regions of CNS studied but catalase (CAT) declined significantly only in the cerebral cortex, hypothalamus and cerebellum. Glutathione reductase (GRd) activity declined in cerebral cortex and hypothalamus in the cytosolic fractions and only in cerebellum in the mitochondrial fraction. It is concluded that age-related decline in the activities of antioxidant enzymes is both region and enzyme specific. The endogenous lipid peroxide was found to be significantly higher (p < 0.05) in the 32 month old animals whereas, lipid peroxidation after incubating the tissue homogenate in air was found to be lower (p < 0.05). The in vitro mitochondrial lipid peroxidation decreased with age. The results indicate that accumulation of lipid peroxides takes place with ageing but the susceptibility of lipid peroxidation decreases in the older animals.     

Cytoprotective activity of annphenone against oxidative stress-induced apoptosis in V79-4 lung fibroblast cells

We have elucidated the cytoprotective effect of annphenone (2,4-dihyroxy-6-methoxy-acetophenone 4-O-beta-d-glucopyranoside) against oxidative stress-induced apoptosis. Annphenone scavenged intracellular reactive oxygen species (ROS) and increased antioxidant enzyme activities. It thereby prevented lipid peroxidation and DNA damage, which was demonstrated by the inhibition of the formation of thiobarbituric acid reactive substance (TBARS), inhibition of the comet tail and decreased phospho-H2A.X expression. Annphenone protected Chinese hamster lung fibroblast (V79-4) cells from cell death via the inhibition of apoptosis induced by hydrogen peroxide (H(2)O(2)), as shown by decreased apoptotic nuclear fragmentation, decreased sub-G(1) cell population and inhibited mitochondrial membrane potential (Deltapsi) loss. Taken together, these findings suggest that annphenone exhibits antioxidant properties by inhibiting ROS generation and thus protecting cells from H(2)O(2)-induced cell damage.     

Loss of latent activity of liver microsomal membrane enzymes evoked by lipid peroxidation. Studies of nucleoside diphosphatase, glucose-6-phosphatase, and UDP glucuronyltransferase

The effects of lipid peroxidation on latent microsomal enzyme activities were examined in NADPH-reduced microsomes from phenobarbital-pretreated male rats. Lipid peroxidation, stimulated by iron or carbon tetrachloride, was assayed as malondialdehyde formation. Independent of the stimulating agent of lipid peroxidation, latency of microsomal nucleoside diphosphatase activity remained unaffected up to microsomal peroxidation equivalent to the formation of about 12 nmol malondialdehyde/mg microsomal protein. However, above this threshold a close correlation was found between lipid peroxidation and loss of latent enzyme activity. The loss of latency evoked by lipid peroxidation was comparable to the loss of latency attainable by disrupting the microsomal membrane by detergent. Loss of latent enzyme activity produced by lipid peroxidation was also observed for microsomal glucose-6-phosphatase and UDPglucuronyltransferase. In contrast to nucleoside diphosphatase, however, both enzymes were inactivated by lipid peroxidation, as indicated by pronounced decreases of their activities in detergent-treated microsomes. According to the respective optimal oxygen partial pressure (po2) for lipid peroxidation, the iron-mediated effects on enzyme activities were maximal at a po2 of 80 mmHg and the one mediated by carbon tetrachloride at a po2 of 5 mmHg. Under anaerobic conditions no alterations of enzyme activities were detected. These results demonstrate that loss of microsomal latency only occurs when peroxidation of the microsomal membrane has reached a certain extent, and that beyond this threshold lipid peroxidation leads to severe disintegration of the microsomal membrane resulting in a loss of its selective permeability, a damage which should be of pathological consequences for the liver cell. Because of its resistance against lipid peroxidation nucleoside diphosphatase is a well-suited intrinsic microsomal parameter to estimate this effect of lipid peroxidation on the microsomal membrane.     

Short-term gemfibrozil treatment reverses lipid profile and peroxidation but does not alter blood glucose and tissue antioxidant enzymes in chronically diabetic rats

In this study, we investigated the efficiency of short-term treatment with gemfibrozil in the reversal of diabetes-induced changes on carbohydrate and lipid metabolism, and antioxidant status of aorta. Diabetes was induced by a single injection of streptozotocin (45 mg/kg, i.p.). After 12 weeks of induction of diabetes, the control and diabetic rats were orally gavaged daily with a dosing vehicle alone or with 100 mg/kg of gemfibrozil for 2 weeks. At 14 weeks, there was a significant increase in blood glucose, plasma cholesterol and triglyceride levels of untreated-diabetic animals. Diabetes was associated with a significant increase in thiobarbituric acid reactive substances (TBARS) in both plasma and aortic homogenates, indicating increased lipid peroxidation. Diabetes caused an increase in vascular antioxidant enzyme activity, catalase, indicating existence of excess hydrogen peroxide (H₂O₂). However, superoxide dismutase (SOD) and glutathione peroxidase (GSHPx) activities in aortas did not significantly change in untreated-diabetic rats. In diabetic plus gemfibrozil group both plasma lipids and lipid peroxides showed a significant recovery. Gemfibrozil treatment had no effect on blood glucose, plasma insulin and vessel antioxidant enzyme activity of diabetic animals. Our findings suggest that the beneficial effect of short-term gemfibrozil treatment in reducing lipid peroxidation in diabetic animals does not depend on a change of glucose metabolism and antioxidant status of aorta, but this may be attributed to its decreasing effect on circulating lipids. The ability of short-term gemfibrozil treatment to recovery of metabolism and peroxidation of lipids may be an effective strategy to minimize increased oxidative stress in diabetic plasma and vasculature.     

Stimulation of thiamine diphosphate activity by ascorbic acid in rat brain microsomes

The effect of ascorbic acid on microsomal thiamine diphosphate activity in rat brain was examined. Ascorbic acid at 0.02–0.1 mM increased the thiamine diphosphate activity by 20–600% and produced a significant amount of lipid peroxide, which was measured with thiobarbiturate under the same conditions as the enzyme. A lag period of about 10 min was observed in the process of stimulation of enzyme activity by ascorbic acid. The stimulation of enzyme activity and the lipid peroxidation induced by ascorbic acid were blocked by metal-binding compounds (EDTA, α,α′-dipyridyl, o-phenanthroline) and an antioxidant (N,N′-diphenyl p-phenylenediamine). GSH significantly enhanced the stimulation of enzyme activity and formation of lipid peroxide by 0.02–0.05 mM ascorbic acid. The effect of GSH was due in part to maintenance of the concentration of ascorbic acid in the medium, since GSH could convert dehydroascorbic acid, an oxidized form of ascorbic acid, to ascorbic acid.     

Over-expression of antioxidant enzymes protects cultured hippocampal and cortical neurons from necrotic insults

There is now considerable knowledge concerning neuron death following necrotic insults, and it is believed that the generation of reactive oxygen species (ROS) and oxidative damage play a pivotal role in the neuron death. Prompted by this, we have generated herpes simplex virus-1 amplicon vectors over-expressing the genes for the antioxidant enzymes catalase (CAT) or glutathione peroxidase (GPX), both of which catalyze the degradation of hydrogen peroxide. Over-expression of each of these genes in primary hippocampal or cortical cultures resulted in increased enzymatic activity of the cognate protein. Moreover, each enzyme potently decreased the neurotoxicity induced by kainic acid, glutamate, sodium cyanide and oxygen/glucose deprivation. Finally, these protective effects were accompanied by parallel decreases in hydrogen peroxide accumulation and the extent of lipid peroxidation. These studies not only underline the key role played by ROS in the neurotoxicity of necrotic insults, but also suggest potential gene therapy approaches.     

Effect of selenium on N-nitrosodiethylamine-induced multistage hepatocarcinogenesis with reference to lipid peroxidation and enzymic antioxidants

We have studied the relationship between antioxidant and anticancer properties of selenium (Se) in multistage hepatocarcinogenesis induced by N-nitrosodiethylamine (DEN). In this study we have observed an increased level of lipid peroxide (LPO) products and decreased antioxidant enzyme activities (superoxide dismutase and catalase) in hepatoma and surrounding liver tissues of cancer-bearing animals. Selenium (Se) was supplemented either before initiation or during initiation and selection/promotion phases of hepatocarcinogenesis and was found to be effective in altering hepatic lipid peroxidation and antioxidant enzyme activities to a statistically significant level measured either in the hepatoma or in the surrounding liver tissues. These alterations inclined towards normal in a time-dependent manner on selenium supplementation. Furthermore, increased levels of lipid peroxidation and decreased levels of antioxidants (superoxide dismutase and catalase) were also observed in distant organs of cancer-bearing rats other than the tumour-bearing site. These alterations are brought back to normal levels upon Se treatment. Our results confirm the fact that Se is particularly protective in limiting the action of DEN by its antioxidant property.