Higher Lipid Peroxidation Research Articles

Oxidative stress and monooxygenase liver function in patients with coronary heart disease and multiple organ dysfunction syndrome

The purpose of the study was to evaluate oxidative stress and liver monooxygenase function in patients with coronary heart disease and multiple organ dysfunction syndrome. Twenty-seven patients with multiple organ dysfunction and 38 patients with an uneventful postoperative period were studied. Oxidative stress was quantified with malon dialdehyde, coupled trienes, hepatocuprein and catalase activity. Liver monooxygenase function was evaluated with antipyrine pharmacokinetics data. On the first postoperative day patients with multiple organ dysfunction were characterized by high lipid peroxidation (conjugated trienes: +84.7%) and significant decrease in liver monooxygenase function (clearance of antipyrine: -38%), whereas control patients had a mild oxidative stress and a slight depression in liver monooxygenase function. On the third to fourth postoperative day in both groups a considerable intensity of lipid peroxidation and increase in liver metabolism was seen. The major difference was observed on postoperative days 10-12. In both groups oxidative stress intensity decreased (conjugated trienes: +34.7%; +12.9%). In the main group liver monooxygenase function was markedly depressed (clearance of antipyrine: -35.6%), whereas in the control group liver metabolism did not deviate from the baseline. The correlation analysis showed a negative relationship between liver monooxygenase function and oxidative stress parameters. Patients with multiple organ dysfunction have considerably more oxidative stress and greater decrease in liver monooxygenase function (one and a half times) than those with an uneventful postoperative period. Lipid peroxidation is one of the main causes of depression of liver monooxygenase function. Slowdown of liver metabolism might change the pharmacokinetic response in patients with coronary heart disease.

Crayfish Procambarus clarkii Retina and Nervous System Exhibit Antioxidant Circadian Rhythms Coupled with Metabolic and Luminous Daily Cycles

Based on previous work in which we proposed midgut as a putative peripheral oscillator responsible for circadian reduced glutathione (GSH) crayfish status, herein we investigated the retina and optic lobe-brain (OL-B) circadian GSH system and its ability to deal with reactive oxygen species (ROS) produced as a consequence of metabolic rhythms and light variations. We characterized daily and antioxidant circadian variations of the different parameters of the glutathione system, including GSH, oxidized glutathione (GSSG), glutathione reductase (GR) and glutathione peroxidase (GPx), as well as metabolic and lipoperoxidative circadian oscillations in retina and OL-B, determining internal and external GSH-system synchrony. The results demonstrate statistically significant bi- and unimodal daily and circadian rhythms in all GSH-cycle parameters, substrates and enzymes in OL-B and retina, as well as an apparent direct effect of light on these rhythms, especially in the retina. The luminous condition appears to stimulate the GSH system to antagonize ROS and lipid peroxidation (LPO) daily and circadian rhythms occurring in both structures, oscillating with higher LPO under dark conditions. We suggest that the difference in the effect of light on GSH rhythmic mechanisms of both structures for antagonizing ROS could be due to differences in glutathione-system coupling strength with the circadian clock.

Nonalcoholic steatohepatitis induced by a high‐fat diet promotes diethylnitrosamine‐initiated early hepatocarcinogenesis in rats

It has been suggested that patients with nonalcoholic steatohepatitis (NASH) may have high risk for liver cancer. However, it is unknown whether high-fat diet (HFD) induced NASH promotes hepatocarcinogenesis. In this study, Sprague-Dawley rats were injected with a low dose of hepatic carcinogen diethylnitrosamine (DEN) and then fed either Lieber-DeCarli control diet (CD) or HFD for 6 weeks. Liver histology and the hepatic placental form of glutathione S-transferase (P-GST) positive foci were examined. Expression levels of proliferating cell nuclear antigen (PCNA), cyclinD1, phosphorylated mitogen-activated protein kinase (MAPK) including extracellular signal-regulated kinase (ERK) and p38, as well as tumor necrosis factor-alpha (TNF-alpha), and nuclear factor-kappaB (NF-kappaB) were measured in the liver. Induction of lipid peroxidation end products (malondialdehyde plus 4-hydroxynonenal) in liver and apoptotic hepatocytes were also assessed. Results showed that HFD-fed rats developed significantly higher incidence and multiplicity of P-GST positive foci along with more fat accumulation, infiltration of inflammatory cells and higher lipid peroxidation in the liver, when compared with rats fed the CD. This high prevalence of hepatic lesions in the liver was accompanied by greater PCNA expression and cyclinD1 protein concentration but little change in hepatocyte apoptosis. HFD feeding elevated hepatic phosphorylated ERK but reduced phosphorylated p38 when compared with the CD feeding. In addition, a significantly higher expression of TNF-alpha mRNA and nuclear NF-kappaB p65 protein were observed in HFD group than in CD group. These data clearly demonstrate that NASH induced by HFD promoted DEN-initiated early hepatocarcinogenesis, which was associated with elevated TNF-alpha/NF-kappaB signaling and MAPK related hepatocyte proliferation.

Abstract B86: Antioxidant enzymes status in carcinoma cervix patients before and after radiotherapy.

Abstract B86 Background and Objectives Cancer is defined as a cellular growth due to uncontrolled cell division. This involves protein synthesis triggered by unusual acceleration of the process of translation, transcription and replication. The extent of free radical induced oxidative stress can be exacerbated by the decreased efficiency of antioxidant defense mechanisms. Low levels of essential antioxidants in the circulation have been found to be associated with an increased risk of cancer. Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) are the major antioxidant enzymes present in the human body that protect against the oxygen toxicity. Oxidative stress may be a consequence of reduced efficiency of these endogenous antioxidants that may render carcinoma cervix patients more vulnerable to oxidative stress. There are reports suggesting a decrease in SOD and other antioxidant enzymes activities and increase in various markers of lipid peroxidation in carcinoma cervix patients. Methods We have undertaken this study to ascertain the possibility of oxidative damage in carcinoma cervix patients by measuring the cytosolic antioxidant enzymes viz., superoxide dismutase (SOD), catalase (CAT), Glutathione (GSH) and lipid peroxidation as well as lactate dehydrogenase levels in circulation of women with cervical carcinoma prior to radiotherapy and at the end of therapy (60~70 Gy tumor dose) in II, IIIA and IIIB and to compare our findings with age matched controls. Results In the present study significant decrease (P<0.05) was observed in SOD, CAT, GSH and significantly high plasma lipid peroxide levels and lactate dehydrogenase levels were observed in carcinoma cervix patients when compared to the normal subjects. Interpretation and Conclusion Antioxidants play a significant role in the aetiology of human cancer.Result of the present study showed involvement of oxidative stress as one of the risk factors, which can be co-related with the severity of the disease,furthermore these biochemical tests has got excellent prognostic significance Citation Information: Cancer Prev Res 2008;1(7 Suppl):B86.

Protective Role of Ca Against NaCl Toxicity in Jerusalem Artichoke by Up-Regulation of Antioxidant Enzymes

The ameliorative effect of external Ca 2+ on Jerusalem artichoke (Helianthus tuberosus L.) under salt stress was studied through biochemical and physiological analyses of Jerusalem artichoke seedlings treated with or without 10 mol L −1 CaCl 2, 150 mmol L −1 NaCl, and/or 5 mmol L −1 ethylene-bis(oxyethylenenitrilo)-tetraacetic acid (EGTA) for five days. Exposure to NaCl (150 mmol L −1) decreased growth, leaf chlorophyll content, and photosynthetic rate of Jerusalem artichoke seedlings. NaCl treatment showed 59% and 37% higher lipid peroxidation and electrolyte leakage, respectively, than the control. The activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) were decreased by NaCl, indicating an impeded antioxidant defense mechanism of Jerusalem artichoke grown under salt stress. Addition of 10 mmol L −1 CaCl 2 to the salt solutions significantly decreased the damaging effect of NaCl on growth and chlorophyll content and simultaneously restored the rate of photosynthesis almost to the level of the control. Ca 2+ addition decreased the leaf malondialdehyde (MDA) content and electrolyte leakage from NaCl-treated seedlings by 47% and 24%, respectively, and significantly improved the activities of SOD, POD, and CAT in NaCl-treated plants. Addition of EGTA, a specific chelator of Ca 2+, decreased the growth, chlorophyll content, and photosynthesis, and increased level of MDA and electrolyte leakage from NaCl-treated plants and from the control plants. EGTA addition to the growth medium also repressed the activities of SOD, POD, and CAT in NaCl-treated and control seedlings. External Ca 2+ might protect Jerusalem artichoke against NaCl stress by up-regulating the activities of antioxidant enzymes and thereby decreasing the oxidative stress.

Interleukin-12p40 contributes to protection against lung injury after oral Yersinia enterocolitica infection

The impact of Yersinia enterocolitica on lung is incompletely understood, so we studied the inflammatory effects of Yersinia oral infection and the influence of IL-12p40 deficiency. Wild-type (WT) and IL-12p40-/- (KO) mice were orally infected with Y. enterocolitica 0:3. After 3 and 21 days, cell viability in bronchoalveolar lavage (BAL) fluid, inflammatory reactions, lipid hydroperoxides, antioxidant enzyme expression and histological changes were studied. An effect on the lung was demonstrated by changes in lactate dehydrogenase, total protein (p <0.001), nitrosative stress and increase numbers of lymphocyte in the BAL fluid. All of these appeared to be IL-12 - independent since statistically significant changes in response to infection (at 21 days) did not differ between WT and KO groups. However, a protective role of IL-12 after infection was suggested by a decrease in cell viability, histopathological changes, different cell populations, higher lipid peroxidation and a decrease in antioxidant enzymes - glutathione peroxidase, superoxide dismutase-2 (p <0.05). The main changes were detected at day 21 suggesting a chronic effect of Yersinia infection and that IL-12 could play a role in the protection against chronic sequelae in the lung. These results demonstrate that Y. enterocolitica infection may induce inflammatory response in lung and that IL-12p40 could contribute to protection against lung injury.

177 POSTER Antiproliferative effects of fluoro-chalcone derivatives in human melanoma A375 cells and peripheral blood mononuclear cells

A series of 2′-hydroxy-chalcones and their oxidative cyclization products, aurones, have been synthesized and tested for their antioxidant and lipoxygenase inhibitory activity. The natural product aureusidin (31) was synthesized in high yield by a new approach. An extensive structure-relationship study was performed and revealed that several chalcones and aurones possess an appealing pharmacological profile combining high antioxidant and lipid peroxidation activity with potent soybean LOX inhibition.

Lipid peroxidation in the cerebrospinal fluid of patients with neurocysticercosis

The variety of symptoms observed in patients with neurocysticercosis (NCC) is associated with the generation of reactive species by inflammatory cells. Reactive species can damage the cell membrane, inducing lipid peroxidation (LP) and giving rise to genotoxic free radicals. In this study we investigated the presence of LP products in cerebrospinal fluid (CSF) and the frequency of DNA damage in peripheral lymphocytes from 25 patients with NCC. Patients with NCC showed higher LP levels compared to controls (n=7), especially patients presenting with severe symptoms. There was a significant correlation between LP and the inflammatory response (Spearman's correlation coefficient 0.75, P<0.01). The presence of free radicals in the central nervous system (CNS) may favour the development of severe clinical symptoms, even in patients under anti-inflammatory treatment but with a poor response. DNA damage correlated with the presence of LP and with symptom severity (correlation coefficient 0.30, P<0.05, and 0.54, P<0.01, respectively). These results demonstrate the generation of oxidative damage in the CNS of patients with NCC, which may be responsible for the severity of the symptoms. LP determination in the CSF of patients with NCC could be used to determine the inflammatory reaction developed.

Overexpression of Arabidopsis thaliana tryptophan synthase beta 1 (AtTSB1) in Arabidopsis and tomato confers tolerance to cadmium stress

Tryptophan (Trp) is an essential amino acid in humans, and in plants, it plays a major role in the regulation of plant development and defence responses. However, little is known about Trp-mediated cadmium (Cd) tolerance. Gene expression analysis showed that Arabidopsis thaliana tryptophan synthase beta 1 (AtTSB1) is up-regulated in plants treated with Cd; hence, we investigated whether this gene is involved in Cd tolerance. Exogenous application of Trp to wild-type Arabidopsis enhances Cd tolerance. Cd tolerance in the Trp-overproducing mutant trp5-1 was associated with high chlorophyll levels and low lipid peroxidation, as indicated by malondialdehyde 4-hydroxyalkenal level, whereas the wild-type developed symptoms of severe chlorosis. Moreover, the Trp-auxotroph mutant trp2-1 was sensitive to Cd. CaMV 35S promoter-driven AtTSB1 enhanced Trp accumulation and improved Cd tolerance in transgenic Arabidopsis and tomato plants without increasing the level of Cd. Moreover, reverse transcription-polymerase chain reaction confirmed that enhanced level of Trp in AtTSB1 transgenic Arabidopsis plants affected the expression of AtZIP4 and AtZIP9 metal transporters, which interfered with Cd ion trafficking, a mechanism of transcriptional regulation that does not exist in wild-type plants. Overexpression of AtTSB1 in transgenic tomato also produced higher Trp synthase-beta enzyme activity than that in wild-type plants. These results implicate that Trp could be involved in Cd defence.

Effects of long-term dietary intake of magnesium on oxidative stress, apoptosis and ageing in rat liver.

In the present study, we investigated the effect of long-term dietary Mg intake on the rate of oxidative stress, apoptosis and ageing in rat livers. To address this issue, rats were fed diets containing either a moderately deficient (0.15 g Mg/kg diet), a standard (0.8 g Mg/kg diet) or a high (3.2 g Mg/kg diet) Mg dose for two years. It is noteworthy that a higher percentage of animal mortality was observed in the lowest Mg diet, as compared to the other groups. Oxidative stress and antioxidant status were evaluated by measuring different enzyme activities, among which glutathione peroxidase activity was significantly reduced when Mg content was decreased in the diet. Moreover, we obtained an activation of caspase-3 and a higher lipid peroxidation in the Mg-deficient group, as compared to the Mg standard group, while no changes in Mg-supplemented group were observed, in accordance with our previously published data in primary cultures of rat hepatocytes (Martin et al., J Nutr 2003). Telomere shortening was measured in rat livers, as a marker of ageing. We found that telomere length was decreased in old animals, as compared to young animals confirming that telomere shortening correlated well with ageing events. Moreover, in old animals, we obtained a decrease of telomere length in the Mg-deficient group, as compared to the other groups. Taken together, our results show that a long-term chronic Mg deficiency led to oxidative stress, apoptosis and an acceleration of ageing in rat livers.

Influence of pre-harvest ozone exposure on quality of strawberry fruit under simulated retail conditions

Strawberries ( Fragaria × ananassa Duch.) were grown under an ozone-enriched atmosphere, and fruit yield, quality, and postharvest behavior under simulated retail storage conditions were investigated. The more ozone sensitive cv. Korona and the less sensitive cv. Elsanta, according to previous studies, were exposed for 2 months to 156 μg m −3 ozone on average, or air without ozone, in controlled-environment chambers. The influence of ozone depended significantly on the cultivar and its susceptibility to oxidative stress. Generally, ozone decreased the contents of ascorbic acid, caused higher lipid peroxidation and lowered sweetness of the fruit. In the case of lipid peroxidation, the effect was strengthened under retail conditions. The ozone stress did not influence yield, size, antioxidative capacity, anthocyanins, or phenolic compounds of fruit. In the more sensitive cv. Elsanta, ozone-induced sepal injuries were detected and the appearance of fruit was thus impaired; glutathione content of fruit also decreased. In contrast, fruit quality of the less sensitive cv. Korona remained almost constant. In general, retail conditions impaired quality of strawberry fruit and in the case of an effect on quality by ozone during fruit development, quality was slightly worse after storage due to the high perishability of the strawberry fruit.

Nonalcoholic steatohepatitis is associated with increased hepatocyte apoptosis, JNK activation and Bax protein

High‐fat diet enriched in n‐6 polyunsaturated fatty acids (PUFA) induces non‐alcoholic steatohepatitis (NASH). The potential mechanisms involved in this process have not been defined. Male Sprague‐Dawley rats were fed ad libitum Lieber‐DeCarli diet at either 35% energy from fat (control) or 71% energy from fat (high‐fat) enriched in n‐6 PUFA for 6 weeks. Histopathological examination showed key features of NASH (steatosis, inflammatory cell infiltration, ballooning degeneration) by the high‐fat diet, which were accompanied with induction of tumor necrosis factor‐a mRNA, high lipid peroxidation products (4‐hydroxynonenal and malondialdehyde), and cytochrome p4502E1. The high‐fat diet caused significantly increased apoptotic cells (3.3 ± 0.4 [Mean ± SD] vs.1.8 ± 0.1/field as assessed by the Terminal dUTP Nick‐End Labeling assay) and also activated caspase‐3 and poly ADP‐ribose polymerase in liver. This increased apoptosis was associated with higher levels of phosphorylated c‐Jun‐NH2‐kinase (JNK) and pro‐apoptotic Bax protein but not anti‐apoptotic proteins Bcl‐2 and Bcl‐xl. This study indicates that the increased oxidative stress, high JNK activation and imbalance of pro‐ and anti‐apoptotic proteins in Bcl‐2 family all contribute to the high fat diet‐induced apoptosis that may play a significant role in the pathogenesis of NASH.

Microcystin-induced oxidative stress in Laeonereis acuta (Polychaeta, Nereididae)

Oxidative stress induced by microcystins was evaluated in an estuarine worm, Laeonereis acuta (Nereididae). Ten organisms were exposed to lyophilized cells of a toxic Microcystisaeruginosa strain RST9501 ( approximately 2 microg/mL microcystins, MC); 10 were exposed to lyophilized cells of a nontoxic Aphanotece sp. strain RSMan92 and 10 were maintained without cyanobacterial cells. Exposure time was 48 h. The enzymatic antioxidant defenses, as well as the oxidative damage, were analyzed. Toxic and nontoxic cyanobacteria lowered catalase activity with no changes in glutathione reductase and glutathione-S-transferase activities. This may have led to toxin intracellular accumulation, which should favor oxidative stress generation, observed by the high lipid peroxide and DNA-protein crosslink levels in the group exposed to MC.

Lipid peroxidation and antioxidant enzymes in rats exposed to cigarette smoke

Summary: Oxidative metabolism in rats exposed to long term cigarette smoking was investigated in this study. Fourty four rats (22 males and 22 females) were used in this study. 11 males and 11 female rats were assigned into cigarette smoke group and 11 male and 11 female rats were used as control group. The rats assigned into passive smoking were exposed to smoke in a unit for 120 minutes a day for five days a week during 16 weeks. At the end of this period, blood samples were collected from all rats. Plasma MDA and ascorbic acid analysis were performed immediately. Haemoglobin levels and GSH-px, SOD and CAT activities were determined in erythrocytes. The results were evaluated to student t-test. It was observed that plazma MDA levels and GSH-px, and CAT activities were high and plasma ascorbic acid levels were low compared with the control group in male and female rats. SOD activities showed no significant differences. As a result, it was concluded that high plasma lipid peroxidation and low ascorbic acid concentrations may be involved in the pathogenicity of cigarette.

Studies on mercuric sulfide, a component of cinnabar, a Chinese herbal medicine, on celluar functions in mouse lung and fibroblasts

Although the cytotoxic effects of mercuric chloride (HgCl2) and methylmercury chloride (MeHg) have been extensively studied, the insoluble mercuric sulfide (HgS) has been the subject of fewer studies. Since the traditional Chinese mineral drug, cinnabar (containing >95% HgS) continues to be used as an ingredient for infant sedation, the pharmacological and toxicological effects of HgS need to be clarified. In previous experiments, HgS and cinnabar were shown to be absorbed from the gastrointestinal tract (GIT) and distributed in various tissues including the lungs. Thus, a preliminarily examination of whether HgS might exert any oxidative stress on a mouse lung was undertaken. HgS reduced GSH content and increased lipid peroxidation in the lung. Further studies on the cytotoxic effects and the possible mechanisms of action of HgS were compared with HgCl2 and MeHg in cultured lung fibroblast V79 cells. The results showed that HgS produced cytotoxicity at a concentration (400–1200 µM)in a dependent manner with IC50 of 795.6 µM, as compared to HgCl2 and MeHg, 8.1 µM and 5.9 µM, respectively. In addition, the HgS induced the phenomena of DNA fragmentation, increasing reactive oxygen species (ROS) and decreasing mitochondrial membrane potential, accompanied by decreased levels of intracellular ATP and GSH and higher lipid peroxidation levels, similar to HgCl2 and MeHg, but with different toxicokinetic properties. These findings provide evidence for understanding the mechanisms underlying the toxic effects of HgS.

The effect of superoxide dismutase deficiency on zinc toxicity in Schizosaccharomyces pombe

Zinc is a metal which is a cofactor in many enzymes and a structural element in zinc finger motifs those are important in relation between DNA and regulator proteins. Little is known about uptake, distribution, toxicity and detoxification of zinc ions in cells. In this study, zinc toxicity and detoxification levels have been compared in wild type and Cu/Zn superoxide dismutase mutant (sod1Delta) cells of the fission yeast Schizosaccharomyces pombe. We evaluated the toxic levels of zinc, total zinc content, lipid peroxidation levels and catalase activities for both strains which were grown in medium containing different concentrations of zinc. sod1Delta mutant showed important growth retardation and has higher lipid peroxidation and catalase activities than wild type. Cu/Zn superoxide dismutase (SOD1) activity of wild type cells was markedly increased when they were treated with elevated levels of zinc. SOD1 mRNA level also significantly increased when the cells treated with higher concentrations of zinc. These results indicate that the mutant cells were more sensitive to zinc stress and seemed to have more oxidative intracellular environment than wild type cells. Our results support the idea that superoxide dismutase is an important factor for zinc detoxification in eukaryotes.

Effect of Lycopene from Tomatoes (Cooked) on Plasma Antioxidant Enzymes, Lipid Peroxidation Rate and Lipid Profile in Grade-I Hypertension

Background: Results from observational studies suggest that the oxidative stress and hyperlipidemic status, which prevails in hypertension, plays an important role in causation of secondary complications. So the aim of the present study is to evaluate the beneficial effect of tomatoes, which are a rich source of lycopene, a relatively new carotenoid known to play an important role in human health and disease. Methods: In this study lipid peroxidation rate was measured by estimating malondialdehyde (MDA) and the activity of plasma enzymes involved in antioxidant activities like superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), glutathione reductase (GR), reduced glutathione (GSH), and serum lipid profile which includes total cholesterol and triglycerides were estimated in a grade I hypertensive group (n = 40) and an age-matched control group (n = 50). Results: Significantly lower plasma antioxidant enzyme activity, very high lipid peroxidation rate and very high serum total cholesterol, triglycerides in the grade I hypertensive group was observed when compared to the control group (p < 0.001). Sixty days of tomato supplementation in the hypertensive group (n = 30) showed a significant improvement in the levels of serum enzymes involved in antioxidant activities and decreased lipid peroxidation rate (F value highly significant), but there were no significant changes in lipid profile (F value insignificant). Conclusion: These findings suggest that tomato lycopene may have considerable natural therapeutic potential as an antioxidant but may not be used as a hypolipidemic agent in hypertension.

Oxidative stress parameters in plasma of Huntington's disease patients, asymptomatic Huntington’s disease gene carriers and healthy subjects

Animal data and postmortem studies suggest a role of oxidative stress in the Huntington's disease (HD), but in vivo human studies have been scarce. To assess the presence of oxidative stress in HD patients and its occurrence relative to clinical symptoms. Oxidative stress markers were determined in plasma of HD patients (n = 19), asymptomatic HD gene carriers (with > 38 CAG repeats) (n = 11) and their respective sex and agematched healthy controls (n = 47 and n = 22) in a cross-sectional study. With adjustment for age and sex, HD patients had higher plasma lipid peroxidation (LP) levels (ratio 1.20, 95% CI 1.09 to 1.32, p < 0.001) and lower reduced glutathione (GSH) levels (ratio 0.72, CI 0.55 to 0.94, p = 0.011) than their age and sex-matched controls. Although considerably younger, HD gene carriers did not differ from HD patients regarding LP and GSH levels, and had higher plasma LP (ratio 1.16, CI 1.02 to 1.32, p = 0.016) and lower GSH than their matched controls (ratio 0.73, CI 0.5 to 1.05). They had higher LP (ratio 1.18, CI 1.02 to 1.34, p = 0.019) and lower GSH (ratio 0.75, CI 0.51 to 1.11) than the healthy subjects matched to HD patients. Oxidative stress is more pronounced in HD patients and asymptomatic HD gene carriers than in healthy subjects. Differences in plasma LP and GSH are in line with the brain findings in animal models of HD. Data suggest that oxidative stress occurs before the onset of the HD symptoms.

Iron-induced oxidative stress in haemodialysis patients: a pilot study on the impact of diabetes

Administration of intravenous iron preparations in haemodialysis patients may lead to the appearance of non-transferrin bound iron which can catalyse oxidative damage. We investigated this hypothesis by monitoring the oxidative stress of haemodialysis patients and the impact of iron and diabetes mellitus herein. Baseline values of serum iron and related proteins, transferrin glycation, non-transferrin bound iron, antioxidant capacity and lipid peroxidation (malondialdehyde) of 11 haemodialysis patients (six non-diabetic and five type 2 diabetes) were compared to those of non-haemodialysis control subjects (non-diabetic and type 2 diabetes). Changes in these parameters were monitored during haemodialysis before and after iron administration. Baseline values of malondialdehyde correlated with ferritin concentration (r = 0.664, P = 0.036) and were elevated to the same extent in non-diabetic and diabetic haemodialysis patients (median of 1.09 compared to 0.60 mumol/l in control persons, P < 0.02). After iron infusion, transferrin saturation increased more markedly in non-diabetic subjects from 28% to 185% vs. from 33% to 101% in diabetic patients (P = 0.008). This increase was accompanied by the appearance of non-transferrin bound iron (5.91 +/- 1.33 micromol/l), a loss in plasma iron-binding antioxidant capacity and a further increase in malondialdehyde which was more pronounced in diabetic patients (from 0.93 +/- 0.30 micromol/l to 2.21 +/- 0.69 micromol/l vs. from 1.21 +/- 0.42 micromol/l to 1.86 +/- 0.56 micromol/l in the non-diabetic subjects, P = 0.046). In haemodialysis patients, higher lipid peroxidation is determined by higher body iron stores. The increase induced by iron infusion is accompanied by a loss in iron-binding antioxidant capacity and is more pronounced in diabetes mellitus.

Corticosterone as a marker of susceptibility to oxidative/nitrosative cerebral damage after stress exposure in rats

There are important individual differences in susceptibility to stress-induced diseases, most of them associated to the hypothalamic-pituitary and sympatho-medullo-adrenal axis functioning. Characterization of individual differences in animals may help to find the origin of this susceptibility. In order to study differences in oxidative and neuroinflammatory consequences in brain after stress exposure, we used an adult, male, outbred (Wistar:Hannover) population of 60 rats. Animals were subjected to 6h of immobilisation stress. Basal (1 week before stress) and post-stress (immediately after stress) plasma corticosterone (CC) was measured for each animal from the tail vein (basal: 239.74+/-19.44 ng/ml at 1500 h). Group H was assigned to animals with 33% higher levels of CC (>279.53 ng/ml) and group L to animals with 33% lower levels of CC (<199.09 ng/ml). After stress, animals with higher plasma CC levels in basal conditions showed higher adrenal response (higher post-stress CC levels) than rats with lower levels of basal CC. Furthermore, rats from H group are more vulnerable to accumulation of oxidative/nitrosative mediators in brain (higher calcium-independent nitric oxide activity and higher lipid peroxidation, by malondialdehyde determination, MDA) and also to the accumulation of proinflammatory mediators (higher PGE(2) levels) whereas showing less antiinflammatory protection (less 15-deoxy-PGJ(2) levels). Statistical analysis, by using ROC curves revealed cut-off values of basal plasma CC predicting animals with higher post-stress MDA and PGE(2) and lower PGJ(2) levels in brain. These data indicate that plasma basal levels of CC are an easily detectable and reproducible parameter for predicting the response of the individuals after an acute stress, providing further support for studies on individual differences.