Activities of brain antioxidant enzymes,lipid and protein peroxidation

Organophosphate pesticides are known to induce oxidative stress and cause oxidative tissue damage, as has been reported in studies concerning acute and chronic intoxication with these compounds.     

Effect of cigarette smoke inhalation on antioxidant enzymes and lipid peroxidation in the rat

Inhalation of cigarette smoke significantly increased glutathione (GSH) content and increased lipid peroxidation without altering the activities of Superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) or glutathione reductase (GR) in the lung (six male Wistar rats). Following intratracheal administration of benzo[a]pyrene (BP), an increase in pulmonary GSH-Px activity, GSH content and lipid peroxidation was observed after 12 h. GSH-Px activity and GSH content returned to control values by 7 and 30 days, respectively, whereas lipid peroxidation in the lung remained significantly greater than the control value for up to 7 days of BP administration. Hepatic activity of SOD was increased significantly, whereas the activities of GSH-Px, catalase, GR, and GSH content were not changed by inhalation of cigarette smoke. On administration of BP, a significant increase in the activities of SOD and GSH-Px was observed at 12 h. After 7 and 30 days, the activities of these antioxidant enzymes were comparable to their respective control group values. No change in the activity of catalase or in the level of lipid peroxidation was noted throughout the entire study period.     

Effect of cadmium on lipid peroxidation and antioxidant enzymes in undernourished weanling rat brain

The effect of early postnatal cadmium exposure on lipid peroxidation and antioxidant enzymes in undernourished weanling rat brain has been studied. The results suggest that undernutrition makes the weanling rat brain more susceptible to the neurotoxic effects of cadmium. Cadmium at a low dose of 1 mg/kg body weight did not produce any changes in lipid peroxidation and antioxidant enzymes in normal weanling rat brain, but caused a significant increase in lipid peroxidation and markedly decreased the activities of antioxidant enzymes like glutathione peroxidase, superoxide dismutase and catalase when subjected to undernutrition.     

Status of lipid peroxidation, glutathione, ascorbic acid, vitamin E and antioxidant enzymes in patients with pregnancy--induced hypertension

The exact pro-oxidant and antioxidant status in pregnancy--induced hypertension patients is still not clear. To add a new insight to the question, changes in the erythrocyte lipid peroxidation products (malondialdehyde; MDA), levels of glutathione (GSH), ascorbic acid and plasma vitamin E (non enzymatic antioxidant parameters) and activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase in erythrocytes were studied in thirty five patients with pregnancy--induced hypertension and thirty five healthy pregnant normotensive cases. It was observed that there was a significant increase in erythrocyte MDA levels, activities of SOD, GPx and a significant decrease in erythrocyte GSH, ascorbic acid, plasma vitamin E levels and catalase activity in patients with pregnancy--induced hypertension when compared to controls. The results of our study have shown higher oxygen free radical production, evidenced by increased levels of MDA and decreased levels of GSH, ascorbic acid, vitamin E and Catalase activity supports the oxidative stress in pregnancy--induced hypertension. The increased activities of antioxidant enzymes may be a compensatory regulation in response to increased oxidative stress. The decreased concentrations of glutathione and antioxidant vitamin status supports the hypothesis that lipid peroxidation is an important causative factor in the pathogenesis of preeclampsia.     

Effects of chloroquine on lysosomal enzymes, NADPH-induced lipid peroxidation, and antioxidant enzymes of rat retina

Chloroquine (1, 5 and 10 mg/kg), given in acute and in chronic (7 and 15 days) treatment schedules, caused characteristic alterations in the lysosomal enzyme system, antioxidant enzymes, NADPH-induced lipid peroxidation, and glutathione content in the retina of the rat. One-half hour and four hours after chloroquine administration, increased free activities of lysosomal enzymes and NADPH-induced lipid peroxidation were observed, associated with a decrease in tissue glutathione content. In contrast to the acute effect, chloroquine, given in 7- and 15-day treatment schedules, had no significant effect on the lysosomal enzyme system, while at the same time a normalization or a decrease in NADPH-induced lipid peroxidation, associated with a significant increase in tissue glutathione content, was noted. Catalase and peroxidase activities were decreased after both the acute and the daily treatment schedules. Superoxide dismutase activity, although increased in the high dose acute study, appeared otherwise little affected by chloroquine treatment.     

黄芪注射液对慢性肺心病患者血中脂质过氧化物及抗氧化酶活性的影响

目的：探讨黄芪注射液对慢性肺心病患者血中脂质过氧化物及抗氧化酶活性的影响。方法：48例慢性肺心病患者随机分为两组，分别用常规治疗（对照组）及常规治疗加用黄芪注射液（治疗组）治疗14d，观察治疗前后血超氧化岐化酶（SOD）、过氧化脂质（LPO）和谷胱甘肽过氧化物酶（GSH—PX）含量，并与20例健康人（健康对照组）比较。结果：慢性肺心病患者血SOD、LPO含量明显高于健康对照组（P〈0．01），OSH—PX明显低于健康对照组（P〈0．05）；治疗组患者治疗后SOD、LPO明显下降（P〈（1．01），GSH—PX明显上升（P〈0．05）；而对照组患者治疗后SOD，LPO和GSH—PX无明显变化（P〉0．05）。结论：黄芪注射液能明显降低慢性肺心病患者增强的脂质过氧化反应，纠正抗氧化酶的失衡。     

The effects of diazinon on lipid peroxidation and antioxidant enzymes in erythrocytes in vitro

Diazinon is one of the most widely used organophosphate insecticides (OPI) in agriculture and public health programs. The aim of this study was to investigate how an OPI, diazinon, affects lipid peroxidation (LPO) and the antioxidant defense system in vitro. For this purpose, two experiments were carried out. In experiment 1, the effects of various concentrations of diazinon on LPO and the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) in erythrocytes were studied. Each diazinon concentration was incubated with a previously prepared erythrocyte samples at +4 degrees C for 0, 60 and 180 min. After incubation, the malondialdehyde (MDA) levels and the activities of SOD, GSH-Px and CAT were determined. In experiment 2, in order to determine the direct effect of diazinon on the activities of SOD, GSH-Px and CAT, the erythrocytes were haemolysed and incubated with the various concentrations of diazinon at +4 degrees C for 0, 60 and 180 min. In experiment 1, MDA levels and the activities of SOD and GSH-Px increased with increasing diazinon concentration and incubation period, but CAT activity remained unchanged. In experiment 2, SOD activity was significantly decreased, and GSH-Px activity was significantly increased. From these results, it can be concluded that in vitro administration of diazinon results in the induction of erythrocyte LPO and changes the activities of antioxidant enzymes, suggesting that reactive oxygen species may be involved in the toxic effects of diazinon.     

Effect of reduced glutathione treatment on selenosis, blood selenium concentration and glutathione peroxidase activity after repeated short-term selenium exposure in buffalo calves

Effects of repeated feeding of selenium, when given alone or along with reduced glutathione, on whole blood selenium levels, selenosis and glutathione peroxidase activity, was studied in buffalo calves. After feeding 2.5 mg/kg of BW sodium selenite, good correlation was found between the onset of selenosis and whole blood selenium concentrations. Adverse effects appeared when the whole blood selenium concentrations increased above 2 microg/ml and mortality occurred when they exceeded 3.4 microg/ml. Reduced glutathione, given i.v. at 5 mg/kg of BW arrested the progress of selenosis and prevented mortality which was 100% in the sodium selenite supplemented group; also a reduced whole blood selenium concentration was noted. Whole blood selenium concentrations were a better and more sensitive indicator of selenium status than glutathione peroxidase activity alone.     

Drug-induced lipid peroxidation in mice—I Modulation by monooxegenase activity,glutathione and selenium status

Feeding male mice for 2 days with sucrose leads to a decrease of total liver glutathione by more than 50 per cent when compared to controls. Such animals were intoxicated with 300 mg/kg paracetamol and upon administration of inducers of the drug-metabolizing system, in vivo and vitro lipid peroxidation in these animals was largely increased as well as the susceptibility to the drug. Pretreatment of the mice with methylcholanthrene led to a 28-fold, with benzo(α)pyrene to a 22-fold, and with phenobarbital to a tenfold increase in ethane exhalation. In vivo administration of various monooxygenase inhibitors showed that all agents effectively inhibit paracetamol-induced lipid peroxidation. It is concluded that phase I metabolism of paracetamol is a prerequisite for the manifestation of drug-induced lipid peroxidation.Selenium deficiency in mice neither affected hepatic levels of glutathione nor its decrease following sucrose feeding, nor glutathione transferase, superoxide dismutase, catalase and glutathione reductase activity. Selenium-dependent glutathione peroxidase activity of selenium-deficient mice, reactive with H₂O₂ as well as with t-butylhydroperoxide, decreased to 5 per cent of the supplemented controls. A glutathione peroxidase activity, which utilized cumenehydroperoxide as a substrate but insensitive to selenium deficiency, was found. Selenium-deficient diethylmaleate-pretreated animals were much more susceptible to paracetamol-induced lipid peroxidation than controls. Supplemented diethylmaleate-pretreated animals showed no signs of lipid peroxidation if treated with 100 mg/kg aminopyrine or ethylmorphine. However, deficient animals exhibited high ethane exhalation rates, drastically increased serum transaminases, loss of hepatic glutathione and mortality upon administration of these drugs. Qualitatively similar results with lower ethane exhalation rates were observed when 125 mg/kg furosemide was administered to diethylmaleate-pretreated selenium-deficient or -adequate mice. Even administration of 200 mg/kg ethoxycoumarin in combination with diethylmaleate lead to significant lipid peroxidation in phenobarbital-induced mice.The results demonstrate that in vivo selenium-dependent glutathione peroxidase plays a predominant role within the glutathione redox couple system. The enzyme protects the liver from peroxidative damage evoked by phase I metabolism of various drug types, as long as sufficient glutathione is available. It is suggested that activated oxygen released from the microsomal monooxygenase is the species responsible for the observed lipid peroxidation accompanied by severe acute liver lesions.     

Protective effect of N-acetylcysteine on reduced glutathione, reduced glutathione-related enzymes and lipid peroxidation in methanol intoxication

The primary metabolic appropriation of methanol is oxidation to formaldehyde and then to formate. These processes are accompanied by formation of superoxide anion and hydrogen peroxide. This paper reports data on the effect of N-acetylcysteine (NAC) on reduced glutathione (GSH) and on activity of some GSH-metabolising enzymes in the liver, erythrocytes and serum of rats intoxicated with methanol (3 g/kg b.w.) during 7 days after intoxication. Methanol administration, increasing concentration of the lipid peroxidation products, decreased the liver glutathione-peroxidase and glutathione reductase (GSSG-R) activities, GSH concentration and total antioxidant status (TAS). The use of NAC after methanol ingestion apparently diminished lipid peroxidation, elevated the GSH level in the liver and erythrocytes, and increased activity of GSH-related enzymes in the serum, erythrocytes and in the liver. These results suggest that NAC exerts its protective effect by acting as a precursor for glutathione, the main low molecular antioxidant and as a free radical scavenger.     

Effect of oral administration of T-2 toxin on glutathione shuttle enzymes, microsomal reductases and lipid peroxidation in rat liver

Effects of T-2 toxin on liver lipid peroxidation, glutathione shuttle enzymes and microsomal reductases have been studied in rats at 8, 16 and 24 hr after feeding a single dose of toxin (2.0 mg/kg) and at 7, 14 and 21 days after feeding of toxin (0.75 mg/kg) daily. Feeding of a single dose of T-2 toxin caused significant increase in liver lipid peroxidation in rats at 8, 16 and 24 hr post treatment. The liver lipid peroxidation was also significantly increased at 14 and 21 days after feeding of 0.75 mg/kg of T-2 toxin daily to rats. The activities of liver GSH-shuttle enzymes, i.e. glutathione peroxidase, glutathione reductase and glucose-6-phosphate dehydrogenase, were significantly higher in rats after both feeding schedules of T-2 toxin. NADPH-cytochrome c reductase activity was significantly lower at 8, 16 and 24 hr in liver of rats fed a single dose of T-2 toxin, whereas NADH-cytochrome b5 reductase was significantly higher until 16 hr and then declined below normal at 24 hr post treatment. In rats fed multiple doses of T-2 toxin, both liver microsomal reductases were significantly reduced. These results suggest that T-2 toxin/or its metabolites in the liver may be involved in the generation of free radicals which cause the observed increase in lipid peroxidation.     

The effect of moderate swimming exercise on antioxidant enzymes and lipid peroxidation levels in children

Strenuous exercise is characterized by increased oxygen consumption and the disturbance between intracellular pro-oxidant and antioxidant homeostasis. Although there are several studies related to an increase in antioxidant enzyme activity in adults doing exercise, the effect of regular exercise on antioxidant enzymes and lipid peroxidation levels has not been examined in children. In our study, the effects of a four week regular swimming exercise on antioxidant enzymes (superoxide dismutase and glutathione peroxidase) activities in erythrocytes and plasma thiobarbituric acid reactive substances (TBARS) levels, an indicator of lipid peroxidation, were investigated in previously untrained healthy children. We found that superoxide dismutase (SOD) activity was increased significantly following a four week swimming course (from 581.1 +/- 146.2 to 791.1 +/- 221.9 U/gHb, P < 0.01). Conversly, plasma TBARS levels were decreased from 1.1 +/- 0.4 to 0.9 +/- 0.3 nmol/ml (P < 0.05). Glutathione peroxidase (GPx) activity appeared to increase following swimming course, albeit not statistically significant (from 45.5 +/- 16.5 to 50.3 +/- 14.8 U/gHb). According to these findings, regular swimming exercise has beneficial effects on antioxidant defence in healthy children.     

Glutathione redox state, lipid peroxide levels, and activities of glutathione enzymes in oltipraz-treated adult Schistosoma mansoni

A decrease in reduced glutathione (GSH) levels in adult Schistosoma mansoni exposed in vitro to the antischistosomal drug oltipraz (OPZ) (20-60 nM) was accompanied by a significant increase in oxidized glutathione (GSSG) levels. The total glutathione (GSH + GSSG) levels also diminished in drug-treated parasites. The activities of the parasite glutathione peroxidase (GPO), utilizing cumene hydroperoxide as a substrate, and glutathione S-transferase (GST), measured 18 hr after in vitro incubation with the drug, were elevated significantly, but there were no significant alterations in the activities of the GPO, utilizing H2O2, or glutathione reductase (GR). Drug-treated worms showed increased lipid peroxidation. In vivo, the proportion of the worms recovered from infected mice given OPZ (100 mg/kg body wt) gradually declined with time, to about 30% of that recovered from infected untreated control mice by day 14 after drug administration, and consisted predominantly of male worms. Accompanying this significant decline in the proportion of worms recovered were significant decreases in the activities of the enzymes GR and GST in drug-exposed worms. On the other hand, a slight initial increase in the GPO activity with cumene hydroperoxide was followed by a return to control values, and the GPO activity with H2O2 was decreased only slightly with time. Interestingly, the 4-hydroxyalk-2-enal aldehydes, known products of lipid peroxidation, inhibited the GST reaction with 1-chloro-2,4-dinitrobenzene (CDNB). The OPZ-induced changes in S. mansoni could increase parasite susceptibility to oxidative attack by host phagocytes, and are probably linked with the antischistosomal action of the drug in vivo.     

Effect of phensuccinal on lipid metabolism, lipid peroxidation, and antioxidant system activity in rabbits with dithiazone-induced diabetes

A three-month administration of phensuccinal improved glucose homeostasis, decreased the levels of total cholesterol, triglycerides, fatty acids, and low-density lipoproteins in the blood serum, and reduced the lipid peroxidation rate as compared to the untreated diabetic control. In addition, phensuccinal increased the content of the antiatherogenic high-density lipoprotein fraction and the related paraoxonase enzyme activity. The preventive effect of phensuccinal with respect to diabetic dyslipidemia development, together with the antioxidant action, show this compound to be a promising therapeutic means of preventing and/or reducing macrovascular complications in diabetic patients.     

Effect of several sesquiterpene lactones on lipid peroxidation and glutathione level.

Seven sesquiterpene lactones isolated from Helenium aromaticum: helenalin, mexicanin I, linifolin A, geigerinin, and from Telekia speciosa: 6 alpha-hydroxy-2,3-dihydroaromaticin, asperilin, telekin have been tested for their hydroxyl radical scavenging activity and effect on lipid peroxidation. All compounds were found to be potent hydroxyl radical scavengers but did not affect lipid peroxidation in vitro. In vivo they exerted pro-oxidative properties and caused glutathione level depletion and elevation in glutathione peroxidase activity.     

The effect of organophosphate insecticide chlorpyrifos-ethyl on lipid peroxidation and antioxidant enzymes (in vitro)

Organophosphates are known primarily as neurotoxins. However, reactive oxygen species (ROS) caused by organophosphates may be involved in the toxicity of various pesticides. Therefore, in this study we aimed to examine how an organophosphate insecticide, chlorpyrifos-ethyl (CE) [0,0-diethyl 0 (3,5,6-trichloro-2-pyridyl) phosphorothioate], affects lipid peroxidation and the antioxidant defense system in vitro. For this purpose, four experiments were carried out. In experiment 1, erythrocyte packets obtained from six (three male, three female) volunteers were divided into six portions, and to each was added CE in both a high concentration range (0, 0.4, 2, 10, 50, 100 g/l) and a low concentration range (0, 0.01, 0.1 g/l). Additionally, each concentration group was divided into five tubes, and incubated at +4 degrees C for 0, 30, 60, 120, and 240 min. After incubation, the levels of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) were determined in the erythrocytes in all tubes. In experiment 2, to examine the effect of CE (or its main metabolites) on the activity of purified, commercially available enzymes, CE at concentrations of 0. 0.01, 0.1, 0.4, and 10 g/l was incubated with purified SOD, GSH-Px and CAT at the concentrations observed in control group at the 0 CE concentration level in experiment 1 for 1 h at room temperature (25 degrees C). In experiment 3, the xanthine-xanthine oxidase system was used to determine whether the activities of SOD, GSH-Px and CAT were inactivated other than by CE, for example by superoxide radicals inducing lipid peroxidation in erythrocytes. Samples with xanthine and xanthine oxidase were mixed and incubated for 1 h at room temperature (25 degrees C). In experiment 4, to determine whether enzyme activities were still inhibited if lipid peroxidation was prevented by exogenous antioxidants, experiment 1 was repeated with the CE concentrations of 0.01, 0.1, 0.4, and 10 g/l by adding butylated hydroxytoluene and vitamin E to the medium. The MDA levels were determined spectrophotometrically. Enzymatic methods were used for the determination of SOD, GSH-Px, and CAT activities. The Friedman test and Wilcoxon's Signed Ranks test were used to compare paired groups. MDA values and GSH-Px activities increased with increasing CE concentration and incubation period (P<0.05), but SOD and CAT activities decreased with increasing CE concentration and incubation period (P<0.01). From these results, it can be concluded that in vitro administration of CE resulted in the induction of erythrocyte lipid peroxidation and significant changes in antioxidant enzyme activities, suggesting that ROS and/or free radicals may be involved in the toxic effects of CE.     

Antidiabetic effect of Punica granatum flowers: Effect on hyperlipidemia,pancreatic cells lipid peroxidation and antioxidant enzymes in experimental diabetes

The present study investigated the effects of Punica granatum aqueous extract (PgAq) on streptozotocin (STZ) induced diabetic rats by measuring fasting blood glucose, lipid profiles (atherogenic index), lipid peroxidation (LPO) and activities of both non-enzymatic and enzymatic antioxidants. Diabetes was induced by single intraperitoneal injection of STZ (60 mg/kg) to albino Wistar rats. The increase in blood glucose level, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), very low density lipoprotein (VLDL), LPO level with decrease in high density lipoprotein cholesterol (HDL-C), reduced glutathione (GSH) content and antioxidant enzymes namely, glutathione peroxidase (GPx), glutathione reductase (GR), glutathione-S-transferase (GST), superoxide dismutase (SOD) and catalase (CAT) were the salient features observed in diabetic rats. On the other hand, oral administration of PgAq at doses of 250 mg/kg and 500 mg/kg for 21 days resulted in a significant reduction in fasting blood glucose, TC, TG, LDL-C, VLDL-C and tissue LPO levels coupled with elevation of HDL-C, GSH content and antioxidant enzymes in comparison with diabetic control group.     

Effects of diphenhydramine and famotidine on lipid peroxidation and activities of antioxidant enzymes in different rat tissues

The potential antioxidant activity of diphenhydramine (histamine H1-receptor antagonist) and famotidine (histamine H2 receptor antagonist) was studied. Diphenhydramine inhibited the spontaneous, Fe(II)-induced and Fe(II)/ascorbate-induced lipid peroxidation, while famotidine showed a biphasic concentration-dependent effect on spontaneous lipid peroxidation (a stimulation by 1 mM and an inhibition by 5 mM) and increased Fe(II)-induced- and inhibited Fe(II)/ascorbate-induced lipid peroxidation in the rat liver and brain. Both drugs decreased *OH-provoked deoxyribose degradation in Fenton-type systems and inhibited O2- -provoked reduction of nitro-blue tetrazolium and ferrycytochrome C, but famotidine effect was stronger than that of diphenhydramine. The significant famotidine-induced inhibition of nitro-blue tetrazolium reduction might be underlain by the stimulation of superoxide dismutase activity. Famotidine and diphenhydramine did not alter the catalase activity in all tissue preparations, except for its concentration of 5 mM (a complete inhibition). The present results suggest a beneficial effect of histamine H1 and H2-blockers, especially famotidine, as antioxidants and/or metal chelators, which might be an additional explanation of their therapeutic action.     

In vivo effects of indomethacin--I. Activity of antioxidant enzymes and lipid peroxidation.

1. The in vivo effects of indomethacin on the activity of antioxidant enzymes and on lipid peroxidation in erythrocytes, liver and small intestines of rats were examined. 2. The activity of the enzymes studied increased or remained unchanged depending on the preparation and model used: treatment with "therapeutic" or "ulcerogenic" dose of indomethacin. 3. Indomethacin inhibited lipid peroxidation in the liver but not in the erythrocytes. 4. The results suggest that the stimulation of antioxidant enzymes, probably through in vivo formed metal complexes, is an alternative mechanism of the antiinflammatory action of indomethacin.     

Effect of zinc on hepatic lipid peroxidation and antioxidative enzymes in ethanol-fed rats

A 3-ml aliquot of 30% ethanol was fed daily to normal as well as zinc-treated (227 mg l(-1)) rats for periods of 2, 4 and 8 weeks. A highly significant increase in the levels of hepatic lipid peroxidation was observed in ethanol-fed rats after 4 and 8 weeks of treatment. On the other hand, the levels of lipid peroxidation came down significantly following ethanol feeding to zinc-treated rats. The activities of glutathione peroxidase (GPx), catalase and superoxide dismutase (SOD) in liver were elevated significantly after ethanol administration to rats for durations of 2, 4 and 8 weeks. Interestingly, zinc treatment to rats given ethanol was able to bring down the elevated levels of SOD, catalase and GPx to within normal limits, However, zinc administration alone did not cause any significant alteration in the activities of these antioxidative enzymes.