Effects of statins on oxidative stress

Free oxygen radicals and insufficient antioxidant enzymes have been implicated in the pathogenesis of hypercholesterolemia (HC). Trace elements function as cofactors in antioxidant enzymes. Antioxidant system and trace elements were investigated in many different studies including HC, but these subjects have not been investigated as a whole in these patients. The aim of the present study was to investigate the antioxidative system and trace elements in hypercholesterolemic patients given fluvastatin therapy. We examined malondialdehyde (MDA), copper zinc-superoxide dismutase (CuZn-SOD), and glutathione peroxidase (GSH-Px) activities together with copper (Cu), iron (Fe), and zinc (Zn) levels in erythrocytes of 35 patients with HC and 27 healthy control subjects. It was found that in patients with HC, erythrocyte MDA was significantly higher than those of controls and erythrocyte CuZn-SOD and GSH-Px activities were significantly lower in patients with HC. Erythrocyte iron levels were significantly higher than those of controls, and erythrocyte copper and zinc levels were significantly lower in patients with HC. Plasma lipid levels and the oxidative state were analyzed in statin-treatment groups given fluvastatin therapy before and after a 3-mo treatment period. In conclusion, we found that fluvastatin has significant antioxidant properties and these effects might be very important in managing dyslipidemia by improving endothelial function.     

Antioxidative metabolism in down syndrome

Down syndrome is the most common cause of mental retardation, affecting 1 in 700–800 liveborn infants. Although numerous biochemical abnormalities accompanying the syndrome have not yet been completely clarified, the antioxidant defense system enzymes have shown to be altered due to increased gene dosage on chromosome 21 and overproduction of superoxide dismutase (SOD-1 or Cu/Zn SOD). The purpose of this study was to investigate the activities of SOD-1 and glutathione peroxidase (GSH-Px) enzymes and the levels of their cofactors zinc (Zn), copper (Cu) and selenium (Se) in plasma of 20 Down syndrome patients. In comparison with age and sex-matched controls (n=15), plasma GSH-Px, SOD, and Cu levels were significantly decreased in the patient group, but Zn and Se concentrations remained unchanged. This study was presented as a poster in 29th Annual Meeting of European Society of Human Genetics held in Genoa in May, 1997.     

Lipid peroxidation and activity of antioxidant enzymes in diabetic rats

We hypothesized that oxygen free radicals (OFRs) may be involved in pathogenesis of diabetic complications. We therefore investigated the levels of lipid peroxidation by measuring thiobarbituric acid reactive substances (TBARS) and activity of antioxidant enzymes [superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT)] in tissues and blood of streptozotocin (STZ)-induced diabetic rats. The animals were divided into two groups: control and diabetic. After 10 weeks (wks) of diabetes the animals were sacrificed and liver, heart, pancreas, kidney and blood were collected for measurement of various biochemical parameters. Diabetes was associated with a significant increase in TBARS in pancreas, heart and blood. The activity of CAT increased in liver, heart and blood but decreased in kidney. GSH-Px activity increased in pancreas and kidney while SOD activity increased in liver, heart and pancreas. Our findings suggest that oxidative stress occurs in diabetic state and that oxidative damage to tissues may be a contributory factor in complications associated with diabetes.     

Docosahexaenoic acid supplementation induces dose and time dependent oxidative changes in C6 glioma cells

In view of the promising use of n-3 polyunsaturated fatty acids (PUFAs) in the prevention and treatment of neurological diseases, it is necessary to ascertain the lack of detrimental oxidative effects. We evaluated short- and long-term effects of 25, 50 and 75 μM docosahexaenoic acid (DHA) supplementation on the oxidative status of C6 glial cells. DHA was incorporated into cells dose and time dependently without any cytotoxic effect. Reactive oxygen species (ROS) level was related to DHA dose and supplementation time. At the lowest dose no significant increase in ROS values was observed at hour 24. Low doses of DHA strengthened the cellular antioxidant defence system as highlighted by a raise in both GPX and catalase activity, and the decreased levels of lipid peroxidation. This effect was pronounced at 24 h of supplementation, almost disappeared at hour 48, while after 72 h an opposite effect was observed: lipid peroxidation increased concomitantly with DHA doses. Therefore, the final effect of DHA on cellular redox status is dependent on dose and time supplementation.     

Antioxidant enzymes as biochemical defenses against phototoxin-induced oxidative stress in three species of herbivorous lepidoptera

Many secondary plant compounds are capable of photoactivation resulting in the production of toxic species of oxygen. One mechanism of defense for insects feeding on phototoxic plants may be the presence of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPOX), and glutathione reductase (GR). The activities of these enzymes were examined in larvae of three lepidoptera: Ostrinia nubilalis, Manduca sexta, and Anaitis plagiata. Highest levels of antioxidant enzyme activity were found in A. plagiata, a specialist feeder on Hypericum perforatum, which contains high levels of the phototoxin hypericin. Larvae of A. plagiata fed leaf discs treated with hypericin exhibited a short-term, concentration-dependent decline in enzyme activity. Longer term studies with A. palgiata fed either the photoxic H. perforatum, or the closely related but non-phototoxic H. calycinum, resulted in increased CAT and GR activity in larvae fed the phototoxic plant whereas SOD activity was not significantly different. These results suggest that CAT and GR may be inducible defenses against phototoxins.     

Docosahexaenoic acid supplementation induces dose and time dependent oxidative changes in C6 glioma cells

In view of the promising use of n-3 polyunsaturated fatty acids (PUFAs) in the prevention and treatment of neurological diseases, it is necessary to ascertain the lack of detrimental oxidative effects. We evaluated short- and long-term effects of 25, 50 and 75 μM docosahexaenoic acid (DHA) supplementation on the oxidative status of C6 glial cells. DHA was incorporated into cells dose and time dependently without any cytotoxic effect. Reactive oxygen species (ROS) level was related to DHA dose and supplementation time. At the lowest dose no significant increase in ROS values was observed at hour 24. Low doses of DHA strengthened the cellular antioxidant defence system as highlighted by a raise in both GPX and catalase activity, and the decreased levels of lipid peroxidation. This effect was pronounced at 24 h of supplementation, almost disappeared at hour 48, while after 72 h an opposite effect was observed: lipid peroxidation increased concomitantly with DHA doses. Therefore, the final effect of DHA on cellular redox status is dependent on dose and time supplementation.     

Tethering the N-terminus of the prion protein compromises the cellular response to oxidative stress

The role of the N-terminal half of the prion protein (PrPC) in normal cellular function and pathology remains enigmatic. To investigate the biological role of the N-terminus of PrP, we examined the cellular properties of a construct of murine PrP, PrP-DA, in which the N-terminus is tethered to the membrane by an uncleaved signal peptide and which retains the glycosyl-phosphatidylinositol anchor. Human neuroblastoma SH-SY5Y cells expressing PrP-DA were more susceptible to hydrogen peroxide and copper induced toxicity than wtPrP expressing cells. The PrP-DA expressing cells had an increased level of intracellular free radicals and reduced levels of superoxide dismutase and glutathione peroxidase as compared to the wtPrP expressing cells. The membrane topology, cell surface location, lipid raft localisation, intracellular trafficking and copper-mediated endocytosis of PrP-DA were not significantly different from wtPrP. However, cells expressing PrP-DA accumulated an N-terminal fragment that was resistant to proteinase K. The data presented here are consistent with the N-terminal region of PrPC having a role in the cellular response to oxidative stress, and that tethering this region of the protein to the membrane compromises this function through the accumulation of a protease-resistant N-terminal fragment, similar to that seen in some forms of human prion disease.     

螺旋藻对小鼠SOD和GSH—Px活力的影响

采用微量测定法,观察螺旋藻对３２只昆明种小白鼠全血中超氧化物歧化酶（ＳＯＤ）和谷光甘肽过氧化物酶（ＧＳＨ－Ｐｘ）活性的影响。结果表明,灌胃螺旋藻试验组（ＳＯＤ）活性（１５７７．１６±１６９．８８ＩＵ／ｇＨｂ）,与相应对照组（１３３６．２７±１５８．２３ＩＵ／ｇＨｂ）比较,ＧＳＨ－Ｐｘ活性（２８．３３±２．３７ＩＵ／ｍｌ）与相应对照组（２４．８７±３．２６ＩＵ／ｍｌ）比较,差别均有非常显著意义（Ｐ＜０．０１）;提示螺旋藻有提高动物ＳＯＤ和ＧＳＨ－Ｐｘ活性的功效     

Salt tolerance of two aquatic macrophytes, <Emphasis Type="Italic">Pistia stratiotes</Emphasis> and <Emphasis Type="Italic">Salvinia molesta</Emphasis>

The physiological responses to NaCl salinity were investigated in two floating aquatic macrophytes, Pistia stratiotes L. and Salvinia molesta L. With the increasing NaCl concentration a decrease in chlorophyll and carotenoid contents was recorded in Salvinia as compared to Pistia. Also a greater increase in H₂O₂ accumulation and lipid peroxidation was observed in the shoot and root tissues of Salvinia as compared to Pistia. The superoxide dismutase, glutathione reductase, catalase and guaiacol peroxidase activities, and ascorbate and glutathione contents increased in Salvinia and Pistia shoot and root tissues in response to NaCl.     

Mechanisms of nitric oxide crosstalk with reactive oxygen species scavenging enzymes during abiotic stress tolerance in plants

Nitric oxide (NO) acts in a concentration and redox-dependent manner to counteract oxidative stress either by directly acting as an antioxidant through scavenging reactive oxygen species (ROS), such as superoxide anions (O₂^?*), to form peroxynitrite (ONOO^?) or by acting as a signaling molecule, thereby altering gene expression. NO can interact with different metal centres in proteins, such as heme-iron, zinc–sulfur clusters, iron–sulfur clusters, and copper, resulting in the formation of a stable metal–nitrosyl complex or production of varied biochemical signals, which ultimately leads to modification of protein structure/function. The thiols (ferrous iron–thiol complex and nitrosothiols) are also involved in the metabolism and mobilization of NO. Thiols bind to NO and transport it to the site of action whereas nitrosothiols release NO after intercellular diffusion and uptake into the target cells. S-nitrosoglutathione (GSNO) also has the ability to transnitrosylate proteins. It is an NO˙ reservoir and a long-distance signaling molecule. Tyrosine nitration of proteins has been suggested as a biomarker of nitrosative stress as it can lead to either activation or inhibition of target proteins. The exact molecular mechanism(s) by which exogenous and endogenously generated NO (or reactive nitrogen species) modulate the induction of various genes affecting redox homeostasis, are being extensively investigated currently by various research groups. Present review provides an in-depth analysis of the mechanisms by which NO interacts with and modulates the activity of various ROS scavenging enzymes, particularly accompanying ROS generation in plants in response to varied abiotic stress.     

Responses of antioxidative system to chilling stress in two rice cultivars differing in sensitivity

The responses of antioxidative system of rice to chilling were investigated in a tolerant cultivar, Xiangnuo-1, and a susceptible cultivar, IR-50. The electrolyte leakage and malondialdehyde content of Xiangnuo-1 were little affected by chilling treatment but those of IR-50 increased. Activities of suoperoxide dismutase, catalase, ascorbate peroxidase and glutathione reductase, and ascorbic acid content of Xiangnuo-1 were remained high, while those of IR-50 decreased under chilling. The results indicated that higher activities of defense enzymes and higher content of antioxidant under stress were associated with tolerance to chilling.     

Oxidative status and serum leptin levels in obese prepubertal children

The prevalence of obesity in children has increased dramatically over the last 20-30 years in developed countries. The aim of this study was to evaluate the oxidative and antioxidant status and any correlation with leptin in obese prepubertal children. A cross-sectional study was made of healthy children from ten elementary schools in the province of Elazig, Eastern Turkey. Blood samples were drawn from children comprising obese and control groups, on a visit to their school in the morning after an overnight fast. The mean body mass index (BMI) was 24.03 +/- 4.09 kg/m(2) in the obese group and was 17.51 +/- 2.33 kg/m(2) in the control group. Mean plasma leptin concentration was significantly higher in the obese children. Homocysteine and malondialdehyde (MDA) levels were also significantly higher in the obese group. In contrast superoxide dismutase (SOD) and glutathione peroxidase activities were significantly decreased in the obese group (p < 0.001). In conclusion, in prepubertal obese children oxidative stress was increased and MDA and homocysteine levels were well correlated with serum leptin level and BMI. In contrast with the increase in oxidative stress, antioxidant activities of SOD and glutathione peroxidase were decreased in obese prepubertal children.     

Oxidative Stress in Vivax Malaria

Malaria is still a leading cause of morbidity and mortality. The increase in lipid peroxidation reported in malaria infection and antioxidant status may be a useful marker of oxidative stress during malaria infection. The aim of this study was to investigate the role of antioxidant enzymes against toxic reactive oxygen species in patients infected with Plasmodium vivax and healthy controls. Malondialdehyde levels, superoxide dismutase, and glutathione peroxidase activities were determined in 91 P. vivax patients and compared with 52 controls. Malondialdehyde levels, superoxide dismutase, and glutathione peroxidase activities were 8.07±2.29 nM/ml, 2.69±0.33 U/ml, and 49.6±3.2 U/g Hb in the patient group and 2.72±0.50 nM/ml, 3.71±0.47 U/ml, and 62.3±4.3 U/g Hb in the control group, respectively. Malondialdehyde levels were found statistically significant in patients with vivax malaria higher than in healthy controls (P<0.001). On the other hand, superoxide dismutase and glutathione peroxidase activities were found to be significantly lower in vivax malaria patients than in controls (P<0.05). There was an increase in oxidative stress in vivax malaria. The results suggested that antioxidant defense mechanisms may play an important role in the pathogenesis of P. vivax.     

Salt Stress Injury Induces Oxidative Alterations and Antioxidative Defence in the Roots of Lemna minor

Lemna minor L. roots were treated with different concentrations of NaCl. Lipid peroxidation was investigated histochemically and biochemically. At higher NaCl concentrations an increase in staining was observed in the root apices as compared to control for lipid peroxidation and loss of membrane integrity as well as an increase in contents of thiobarbituric acid reactive substance and peroxide. Both the non-enzymic antioxidants, ascorbate and glutathione increased with the NaCl concentration in the roots. Whereas an increase in superoxide dismutase, guaiacol peroxidase, and glutathione reductase activities were marked, catalase activity decreased in the roots under NaCl stress. This revised version was published online in July 2006 with corrections to the Cover Date.     

Alterations of serum selenium, zinc, copper, and iron concentrations and some related antioxidant enzyme activities in patients with cutaneous leishmaniasis

The aim of this study was to measure the alterations in serum selenium (Se), copper (Cu), zinc (Zn), and iron (Fe) concentrations and their carrier proteins, ceruloplasmin (Cp), transferrin (Tf) albumin, and related antioxidant enzyme activities, erythrocyte Cu-Zn Superoxide dismutase (Cu-Zn SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in patients with cutaneous leishmaniasis (CL). Erythrocyte Cu-Zn SOD activities, serum Cu concentrations, and Cp levels were found to be significantly higher in the patients group than those of controls. However, GSH-Px and CAT activities and Se, Zn, Fe, and Tf levels were lower in patients than in the control subjects. There were positive important correlation’s between Cu-Zn SOD and Cp, Cu-Zn SOD and Cu, Cp and Cu, GSH-Px and Se, and Fe and CAT in the patients group. Our results showed that serum essential trace elements Se, Zn, Cu, and Fe concentrations and their related enzymes Cu-Zn SOD, GSH-Px, and CAT activities change in CL patients. The changes may be a part of defense strategies of organism and are induced by the hormonelike substances.     

Oxidative stress responses during cassava post-harvest physiological deterioration

A major constraint to the development of cassava (Manihot esculenta Crantz) as a crop to both farmers and processors is its starchy storage roots’ rapid post-harvest deterioration, which can render it unpalatable and unmarketable within 24–72 h. An oxidative burst occurs within 15 min of the root being injured, that is followed by the altered regulation of genes, notably for catalase and peroxidase, related to the modulation of reactive oxygen species, and the accumulation of secondary metabolites, some of which show antioxidant properties. The interactions between these enzymes and compounds, in particular peroxidase and the coumarin, scopoletin, are largely confined to the vascular tissues where the visible symptoms of deterioration are observed. These, together with other data, are used to develop a tentative model of some of the principal events involved in the deterioration process.     

Oxidative stress responses during cassava post-harvest physiological deterioration

A major constraint to the development of cassava (Manihot esculenta Crantz) as a crop to both farmers and processors is its starchy storage roots' rapid post-harvest deterioration, which can render it unpalatable and unmarketable within 24–72 h. An oxidative burst occurs within 15 min of the root being injured, that is followed by the altered regulation of genes, notably for catalase and peroxidase, related to the modulation of reactive oxygen species, and the accumulation of secondary metabolites, some of which show antioxidant properties. The interactions between these enzymes and compounds, in particular peroxidase and the coumarin, scopoletin, are largely confined to the vascular tissues where the visible symptoms of deterioration are observed. These, together with other data, are used to develop a tentative model of some of the principal events involved in the deterioration process. Abbreviations: ACMV, African cassava mosaic virus; AFLP, amplified fragment length polymorphism; CAT, catalase; cDNA, complementary deoxyribonucleic acid; CIAT, International Centre for Tropical Agriculture; Cu/ZnSOD, copper/zinc superoxide dismutase; DAB, 3,3-diaminobenzidine tetrahydrochloride; DPPH, 1,1-diphenyl-2-picrylhydrazyl; FeSOD, iron superoxide dismutase; FW, fresh weight; GUS, -glucuronidase; HPTLC, high-performance thin-layer chromatography; HR, hypersensitive response; IEF-PAGE, isoelectric focusing polyacrylamide gel electrophoresis; MAS, marker-assisted selection; MeJa, methyl jasmonate; MnSOD, manganese superoxide dismutase; NADPH, nicotinamide adenine dinucleotide phosphate (reduced form); NBT, nitroblue tetrazolium; PAL, phenylalanine ammonia-lyase; PCD, programmed cell death; PCR, polymerase chain reaction; POX, peroxidase; PPD, post-harvest physiological deterioration; QTL, quantitative trait loci; ROS, reactive oxygen species; RT, room temperature; SAR, systemic acquired resistance; SDS, sodium dodecyl sulfate; SOD, superoxide dismutase     

Antioxidant enzymes of the black swallowtail butterfly,Papilio polyxenes,and their response to the prooxidant allelochemical,quercetin

The black swallowtail butterfly larvae, Papilio polyxenes, are specialist feeders that have adapted to feeding on plants containing high levels of prooxidant allelochemicals. Third, fourth, and fifth instar larvae were tested for their antioxidant enzyme activities, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPOX), using 850-g supernatants from whole-body homogenates. The overall antioxidant enzyme profile for P. polyxenes was high compared to other insects, with activities ranging as follows: SOD, 1.1–7.5; CAT, 124–343; GR, 1.0–7.5; and GPOX, 0 units. To determine whether these antioxidant enzymes were inducible, P. poly xenes larvae were given a prooxidant challenge by dipping parsley leaves (their diet in the initial studies) in solutions of quercetin, such that the leaves became coated with this prooxidant flavonoid. Mid-fifth instar larvae fed on quercetin-coated leaves were assayed for antioxidant enzyme activities as was previously done with the larvae fed the standard diet. Food consumption and quercetin intake were monitored. SOD activity was increased almost twofold at the highest quercetin concentration tested. CAT and GR activity, on the other hand, were inhibited by increased quercetin consumption, with GR activity completely inhibited at the highest quercetin concentration after 12 h of feeding. GPOX activity, not present in control insects, was also not inducible by a quercetin challenge. These studies point out the key role that the antioxidant enzymes play in insect defenses against plant prooxidants.     

Increased antioxidant activity in Cassia seedlings under UV-B radiation

Cassia auriculata L. seedlings were irradiated with ultraviolet B (UV-B) in an environment-control chamber. The two doses assayed (7.5 and 15.0 kJ m⁻²) induced oxidative damage with an increase in lipid peroxidation and hydrogen peroxide and a decrease in chlorophyll and total phenol contents. The ascorbate and dehydroascorbate content as well as the reduced glutathione/oxidized glutathione content and ratio were significantly increased. The UV-B stress led to significant increases of the activity of superoxide dismutase, catalase, peroxidase and polyphenol oxidase. It is suggested that Cassia seedlings try to counteract high concentrations of oxygen species produced under UV-B stress through a co-ordinated increase in the contents and activities of antioxidants involved in their detoxification.