Gene affecting superoxide dismutase activity linked to the histocompatibility complex in H-2 congenic mice.

The activity of cyanide-sensitive, Cu-Zn superoxide dismutase (SOD) was studied in liver sytosols from H-2 congenic strains of mice. Higher SOD activity was found in livers of mice having H-2b/A.BY, B10, and C3H.SW/haplotypes than in those of H-2a, H-2k and H-2d haplotypes. Segregation studies supported these correlations. In H-2 recombinant strains of mice, the genes influencing the liver SOD activity occur, as ascertained by mapping techniques, at or near the H-2d region of the major histocompatibility complex.

Platelet membrane fluidity and plasma malondialdehyde levels in Alzheimer's demented patients with and without family history of dementia.

Platelet membrane fluidity (PMF) was measured with three different fluorescent probes, 1,6-diphenyl-1,3,5-hexatriene (DPH), 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene (TMA-DPH), 3-(p-phenyl-1,3,5-hexatrienyl)phenyl-propionic acid (DPH-PA), which labeled different parts of the bilayer (the hydrophobic core and the positively and negatively charged regions, respectively) in Alzheimer's disease (AD) patients with and without a family history of dementia, and in a control group. In support of earlier findings in the literature, significantly increased PMF was found by the application of DPH in both groups with AD. The use of the fluorescence probe TMA-DPH, however, revealed no differences between the groups. In contrast, significant rigidification was observed with DPH-PA, but only in the AD group with a positive family history of dementia. The plasma malondialdehyde levels appeared to be similar in each group. Our findings are discussed in light of the controversies regarding the value of PMF measurements in AD.

Oxidative stress and antioxidant defense mechanism in glomerular diseases.

The changes in red blood cell (RBC) lipid peroxidation [measured via the malonyl dialdehyde (MDA) concentration], reduced (GSH), and oxidized glutathione (GSSG) levels, hemoglobin (Hb) oxidation and antioxidant enzyme [catalase (Cat), glutathione peroxidase, and superoxide dismutase (SOD)] activities were studied in 45 pediatric patients with various glomerular diseases [minimal change nephrotic syndrome (MCNS) in relapse or in remission, lupus nephropathy (SLE), poststreptococcal glomerulonephritis (APSGN), IgA nephropathy (IGA gn)], and in 20 adult patients with IGA gn and also in 15 pediatric and 14 adult controls. The in vitro effects of hydrogen peroxide [acetyl phenylhydrazine (APH) test] on the GSH and Hb metabolisms were likewise investigated. There was an increased oxidative stress in MCNS with relapse, IGA gn, SLE gn, and APSGN, which could be detected in the GSH and Hb oxidation and in the lipid peroxidation on the peripheral RBC-s. The RBC SOD and Cat activities were significantly lower in all patients than in the controls. The RBC GSSG level was significantly elevated in all patients, with the exception of MCNS in remission. This stimulated a compensatory GSH production in MCNS with relapse and in IGA gn, but not in SLE or APSGN. The regeneration of GSH from GSSG was reduced in MCNS with relapse, SLE, and IGA gn, but not in APSGN. In remission, the GSH-GSSG redox system normalizes, but in vitro the APH test stimulates an intensive Hb oxidation. In conclusion, there is a correlation between the presence of active glomerular disease and the evidence of oxidative changes in the various parameters measured in peripheral RBCs.

The pathogenesis of L-arginine-induced acute necrotizing pancreatitis: inflammatory mediators and endogenous cholecystokinin.

This study was aimed at an assessment of the role of oxygen-derived free radicals, cytokines and endogenous cholecystokinin (CCK) in the pathogenesis of L-arginine (Arg)-induced acute pancreatitis in rat. We measured the levels of malonyl dialdehyde (MDA), glutathione peroxidase (GPx), catalase and superoxide dismutase (Mn- and Cu, Zn-SOD) in pancreatic tissue, the serum levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6) and CCK, and evaluated the protective effect of the xanthine oxidase inhibitor allopurinol and a novel CCK receptor antagonist KSG-504. Acute pancreatitis was induced in male Wistar rats by injecting 2x 250 mg/100 g body weight of Arg intraperitoneally in an 1-h interval, as a 20% solution in 0.15 M NaCl. Control rats received the same quantity of glycine. 200 mg x kg(-1) allopurinol 30 min before the first Arg treatment or 50 mg x kg(-1) KSG-504 30 min before and 6, 18 and 36 h after the first Arg injection was administered subcutaneously. Rats were killed at 6, 12, 24 and 48 h following Arg administration, and acute pancreatitis was confirmed by a serum amylase level elevation and typical inflammatory features observed microscopically. The serum level of amylase reached the peak level at 24 h after the Arg injection (30,800 +/- 3,813 versus 6,382 +/- 184 U x L(-1) in the control) and normalized at 48 h. The tissue concentration of MDA was significantly elevated at 24 h, and reached the peak value at 48 h (5.00 +/- 1.75 versus 0.28 +/- 0.05 nM x mg(-1) protein in the control). The catalase and Mn-SOD activities were significantly decreased throughout the study, while the GPx activity was significantly reduced at 6 and 12 h, and the Cu, Zn-SOD activity was significantly lower at 12 h after the Arg injection as compared with the controls. Both the TNF-alpha and the IL-6 levels were already elevated significantly at 12 h and peak at 24 h versus the controls (19.1 +/- 7.9 U x mL(-1) and 57.6 +/- 11.2 pg x mL(-1) versus 3.1 +/- 0.8 U x mL(-1) and 15.2 +/- 3.1 pg x mL(-1), respectively). No significant changes in plasma CCK levels were observed. Allopurinol treatment markedly reduced the serum amylase elevation (12.631 +/- 2.257 U x L(-1) at 24 h), prevented the increase in tissue MDA concentration (0.55 +/- 0.09 nM x mg(-1) protein at 48 h) and significantly ameliorated the pancreatic edema, necrosis and inflammation at 48 h after Arg administration. KSG-504 administration did not exert any beneficial effect on the development of histopathological changes neither modified the serum amylase or cytokine levels. Oxygen-derived free radicals and cytokines are involved, while endogenous CCK does not seem to play a role in the pathogenesis of Arg-induced acute pancreatitis.

Oxidative stress changes in L-arginine-induced pancreatitis in rats.

The important role of oxygen radicals in acute experimental pancreatitis was demonstrated by study of the changes in the antioxidant system in the blood, liver, kidney, and pancreas of rats after the administration of a large quantity of L-arginine (L-Arg). The changes in lipid peroxidation and in reduced and oxidized glutathione were followed, as well as the activities of peroxide-decomposing enzymes (glutathione peroxidase and catalase) and H2O2-producing superoxide dismutases. The results demonstrated that "oxidative stress" develops and acute pancreatitis appears rapidly after L-Arg treatment. Oxidative stress symptoms are expressed 24 h after the final treatment. Slow restitution of the studied antioxidant system can be demonstrated as early as after 48 h.

Altered peroxide metabolism in erythrocytes from children with cystic fibrosis.

The superoxide dismutase and catalase activities and the lipid peroxidation values in the blood of healthy volunteers were compared with those of children of various ages and of both sexes with cystic fibrosis and with those of the heterozygous parents of these children. The red blood cell superoxide dismutase and catalase activities in children with cystic fibrosis and in their parents are significantly increased. At the same time, the lipid peroxidation of the red blood cells (the quantity of thiobarbituric acid reactive substance) is significantly reduced.

Comparison of antioxidant red blood cell enzymes in premature and full-term neonates.

Earlier investigations extended exclusively to comparisons of the red blood cells (RBC) Cu,Zn-superoxide dismutase in neonates of various ages. We have now carried out comparative measurements on the activities of RBC catalase and glutathione peroxidase from the same source. Besides the enzymes, we also measured the lipid peroxidation (LP). The differences between the RBC of premature and full-term neonates were found to be significant. The lower antioxidant enzymatic activity and LP level in premature infants are explained by the immaturity of the biochemical systems and the different lipid composition of the RBC membranes.

Examination of the role of oxygen free radicals in bronchial asthma in childhood.

The antioxidant enzyme activities, the lipid peroxidation level, the parameters of glutathione metabolism, and the proportion of haemoglobin oxidation products were determined during the symptom-free period of childhood bronchial asthma. A decreased catalase activity and a significantly reduced glutathione instability were demonstrated as compared to the controls. The results indicate that antioxidant protection of the haemoglobin molecule in asthmatic children is considerably decreased.

Simple method for the measurement of antioxidants.

Washed red blood cells from preserved blood were used to elaborate a method suitable for the examination of red blood cell deformability and for the detection of changes in oxidative stress, i.e. for the determination of lipid peroxidation and antioxidant enzyme activity changes. The oxidative stress was induced by treatment of red blood cells with hydrogen peroxide.

The effects of Oradexone and Ambroxol pretreatment of the oxidative sensitivity of the red blood cells in preterm infants.

The antioxidant enzyme activities and lipid peroxidation in the red blood cells of cord blood were investigated and compared at different gestation times in preterm and full-term neonates, with and without pretreatment of the pregnant mothers with Oradexone (Dexamethasone) or Ambroxol. Administration of the two drugs not only stimulated the lung surfactant system, but also exerted favourable effects on the antioxidant enzyme activities while the lipid peroxidation was decreased.

In vitro antiproliferative effects of tricyclic psychopharmaceutical agents and synergism with some resistance modifiers.

Some of the phenothiazines and dibenz[b,f]azepines exert an antiproliferative effect on HEp-2 and rat prolactinoma cells. The same compounds also have effects on different membrane-bound biochemical events, such as H2O2 formation and the peroxide-generated chemiluminescence of polymorphonuclear leukocytes. The superoxide dismutase inhibition by 7,8-dioxochlorpromazine and 6,9-dioxochlorpromazine have some relation to the growth inhibitory action on the growth of HEP-2 and prolactinoma cells in vitro. The antiproliferative effects of phenothiazines were synergized with resistance modifiers like verapamil, omeprazole and tubulozole-C, due to increased drug-influx or decreased drug-efflux and due to possible action on the cytoskeleton.

Organophosphate effects on antioxidant system of carp (Cyprinus carpio) and catfish (Ictalurus nebulosus).

The effect of the organophosphate insecticide Dichlorvos on antioxidant enzymes and other oxidative and redox parameters of carp (Cyprinus carpio L.) and catfish (Ictalurus nebulosus) were studied. Changes in superoxide dismutase, catalase, glutathione peroxidase, and in the case of carp acetylcholinesterase activities were studied in tissue homogenates. Other parameters studied: changes of lipid peroxidation, reduced glutathione and the amounts of two radicals, superoxide and hydroxyl radicals are compared. Our results showed that the organophosphate tested, besides its inhibitory effect on acetylcholinesterase--or together with it--induces changes characteristic of "oxidative stress."

The activation by magnesium treatment of anti-oxidants eliminating the oxygen free radicals in Drosophila melanogaster in vivo.

Drosophila melanogaster adults of the Oregon R and Canton S wild-type stocks were fed for 24 h with 0.10 M, 0.25 M and 0.50 M MgCl2 in 1 per cent sugar solution. This treatment resulted in a significant increase (10-50 per cent) in the activities of the enzymes superoxide dismutase (SOD) and catalase as well as in the concentration of the non-enzymatic antioxidant glutathione (GSH). The increased activities could be due to the increased synthesis caused by the Mg treatment.

Changes and correlations of antioxidant enzymes, lipid peroxidation and serum neutral lipids due to haemodialysis treatment in chronic uraemic patients.

A study was made of the changes in the activities of the antioxidant enzymes superoxide dismutase and catalase in the blood of chronic uraemic patients before and after haemodialysis. Changes in serum lipids (primarily neutral lipids), lipoproteins and lipid peroxidation were also followed. Before haemodialysis, antioxidant enzyme activities decreased, while lipid peroxidation increased both in the plasma and in the RBC haemolysates. Quantitative changes in the lipids increased the risk factors. Haemodialysis moderated these risk factors and a tendency to improvement was observed.

Effects of Gramoxone-induced reactive oxygen radicals on eicosanoid synthesis of mouse lung.

1. Studies were made to prove that a shift in the eicosanoid metabolism plays a role in the lung-damaging action of paraquat, the active ingredient of Gramoxone, in mice. 2. An attempt was made to inhibit the eicosanoid metabolism with acetylsalicylic acid (Aspisol). Among others, it was found that the metabolic effect impaired by paraquat is influenced in a favourable direction by Aspisol treatment, including the % of survival, the lipid peroxidation values and the superoxide dismutase activity in the lung. 3. At the same time, as a prostacyclin synthesis activator, paraquat participates in the efforts of the organism to eliminate the toxic material, but it later weakens the defence mechanisms by enhancing thromboxane A2 synthesis, and it initiates pulmonary fibrosis, which cannot then be averted with Aspisol.

Effects of Gramoxone and cooling on the antioxidant enzymes of frog (Rana esculenta).

The effects of paraquat, the active ingredient of Gramoxone, were studied on frogs (Rana esculenta) kept at 4 degrees C or 20 degrees C, to establish its effects on the survival, the antioxidant enzyme system and the lipid peroxidation of the tissues (liver and lung). The lower temperature was found to increase the survival. The activities of the antioxidant enzymes were decreased or not influenced by the LD50 of paraquat at the lower temperature, whereas the LD100 often resulted in a significant enzymatic activity increase. It was an important finding that the lipid peroxidation of the lipid decreased in response to paraquat at 4 degrees C, but increased at 20 degrees C. The lipid peroxidation of the lung increased at both temperatures.

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.

Effects of diethyl-dithiocarbamate on antioxidant system in carp tissue.

The influence the pro- and antioxidant values the diethyl-dithiocarbamate (DDTC) in different concentrations in carp tissues was studied. From antioxidant enzyme superoxide dismutase, catalase and glutathion peroxidase activity changes were studied in tissue homogenates. Beside enzyme activities tissue lipid peroxidation (LP), reduced glutathione (GSH) and hydroxyl radical loading of the tissues were measured. Our results indicate that DDTC affects antioxidant parameters by generating GSH excess, not loading the cells thereby with "oxidative stress".

In vivo redox changes in some organs in response to Gramoxone.

The effects of Gramoxone on the redox state potential (E'0) of the liver, heart, skeletal muscle and lung of guinea-pig were examined at different times. The E'0 values were compared with control measurements. Gramoxone was found to cause mainly a significant E'0 increase with time in lung tissues. This lends support to the general experience that the primary target organ for paraquat (PQ) toxicity is the lung. It is suggested as explanation of the observation that the lung is most actively connected with molecular oxygen.

Comparative antioxidant enzyme study in freshwater fishes. II. Distribution of antioxidant enzymes and lipid peroxidation in omnivorous fish organs.

Comparative studies were performed on the activities of superoxide dismutases, catalase and glutathione peroxidase in organ homogenates from three omnivorous fishes, the barbel, crucian carp and common carp. The lipid peroxidation and protein contents of organ homogenates were also compared. These comparative measurements primarily provide control values for subsequent toxicological examinations. The highest total superoxide dismutase activities were found in the liver or roe, kidney, heart and spleen in every cases. The antioxidant enzyme activities and other studied parameters of the organ homogenates partly appear to depend on the feeding mode, but are rather characteristic of the fish variety.