Methamphetamine causes lipid peroxidation and an increase in superoxide dismutase activity in the rat striatum

The administration of methamphetamine to experimental animals results in damage to nigrostriatal dopaminergic neurons. In the present study, we demonstrated that both the acute repeated and the chronic administration of methamphetamine causes an increase in thiobarbituric acid reactive substances, which are indicators of lipid peroxidation, and superoxide dismutase activity in the rat striatum. The results of present study strengthen the notion that reactive oxygen species may play an important role in the methamphetamine-induced neurotoxicity.     

The effect of starvation of lipid peroxidation in synaptosomal and mitochondrial factions of various brain structures

Content of lipid hydroperoxides (LHP) and malonic dialdehyde (MDA) was measured in homogenates of rat brain cortex (limbic, sensomotor and orbital cortex) and subcortex brain structures (hypothalamus, medulla oblongata, and midbrain) and in their synaptosomal and mitochondrial fractions within various periods of starvation 1, 2, 3, 5 and 7 days. Lipid peroxidation was shown to intensify distinctly in the brain regions studied especially in the sensomotor cortex only after relatively long-term starvation during 5-7 days. The rate of lipid peroxidation was considerably higher in mitochondrial fractions of these brain structures studied than in the synaptosomes; high contents of LHP and MDA was found in mitochondria. Activation of lipid peroxidation appears to be distinctly responsible for impairment of the structure and functional components of nervous cells occurring during long-term starvation.     

Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation

Nitric oxide (NO) and superoxide are both constitutive products of the endothelium. Because NO is readily inactivated by superoxide, the bioactivity of endothelium-derived NO (EDNO) is dependent on local activity of superoxide dismutase (SOD). We examined the effects of chronic inhibition of copper-zinc SOD (CuZnSOD) using a rat model of dietary copper restriction. Male weanling Sprague-Dawley rats were fed a Cu-deficient diet and received either no Cu replacement (Cu-deficient) or Cu in the drinking water (Cu-sufficient). Compared with Cu-sufficient animals, Cu-deficiency was associated with a 68% reduction in CuZnSOD activity and a 58% increase in vascular superoxide as estimated by lucigenin chemiluminescence (both P < .05). Compared with Cu-sufficient animals, arterial relaxation in the thoracic aorta from Cu-deficient animals was 10-fold less sensitive to acetylcholine, a receptor-dependent EDNO agonist, but only 1.5-fold less sensitive to A23187, a receptor-independent EDNO agonist, and only 1.25-fold less sensitive to authentic NO (all P < .05). In contrast, acute inhibition of CuZnSOD with 10 mM diethyldithiocarbamate produced a more uniform reduction in sensitivity to acetylcholine (8-fold), A23187 (10-fold), and NO (4-fold; all P < .001). Cu-deficient animals demonstrated a 2.5-fold increase in plasma-esterified F2-isoprostanes, a stable marker of lipid peroxidation, that correlated inversely with arterial relaxation to acetylcholine (R = -.83; P < .0009) but not A23187 or authentic NO. From these findings, we conclude that chronic inhibition of CuZnSOD inhibits EDNO-mediated arterial relaxation through two mechanisms, one being direct inactivation of NO and the other being lipid peroxidation that preferentially interrupts receptor-mediated stimulation of EDNO.     

Mitochondrial respiratory enzyme function and superoxide dismutase activity following brain glutathione depletion in the rat

In substantia nigra from patients with Parkinson's disease, there are decreased levels of reduced glutathione (GSH) and diminished activities of mitochondrial complex I and alpha-ketoglutarate dehydrogenase (alpha-KGDH), along with increased activity of superoxide dismutase (SOD). However, the interrelationship among these events is uncertain. We now report the effect of decreased brain GSH levels on SOD and mitochondrial respiratory enzyme activity in rat brain. In addition, we have investigated the ability of thioctic acid, an endogenous antioxidant, to alter these parameters. Unilateral or bilateral intracerebroventricular (ICV) administration of buthionine sulphoximine (BSO; 1 x 3.2 mg or 2 x 1.6 mg) over a 48-hr period reduced cortical GSH by 55-70%. There was no change in the activity of complex I, II/III, or IV or of citrate synthase in cortex. Similarly, there was no alteration of mitochondrial or cytosolic SOD activity. Thioctic acid (50 or 100 mg/kg IP) alone had no effect on cortical GSH levels in control animals and did not reverse the decrease in GSH levels produced by unilateral or bilateral ICV BSO administration. Thioctic acid (50 or 100 mg/kg IP) had no overall effect on complex I, II/III, or IV or on citrate synthase activity in control animals. Thioctic acid also did not alter cortical mitochondrial respiratory enzyme activity in BSO-treated rats. At the lower dose, thioctic acid tended to increase mitochondrial and cytosolic SOD activity in control animals and in BSO-treated rats. However, at the higher dose, thioctic acid tended to decrease mitochondrial SOD activity. Overall, there was no consistent effect of thioctic acid (50 or 100 mg/kg IP) on SOD activity in control or BSO-treated animals. This study shows that BSO-induced glutathione deficiency does not lead to alterations in mitochondrial respiratory enzyme activity or to changes in SOD activity. GSH depletion in Parkinson's disease therefore may not account for the alterations occurring in complex I and mitochondrial SOD in substantia nigra. Thioctic acid did not alter brain GSH levels or mitochondrial function. Interestingly, however, it did produce some alterations in SOD activity, which may reflect either its antioxidant activity or its ability to act as a thiol-disulphide redox couple.     

Effect of dimethyl sulfoxide pretreatment on activities of lipid peroxide formation, superoxide dismutase and glutathione peroxidase in the mouse liver after whole-body irradiation

We investigated the effects of dimethyl sulfoxide (DMSO) on radiation damage in the mouse. DMSO (i.p. 0.11 g/mouse) administered 30 min before exposure protected the mice from the gamma-whole body irradiation: the 30 days lethality was significantly decreased from 44% to 16% (P < 0.05). The contents of thiobarbituric acid reactive substances(TBA-RS) in the mouse liver increased linearly between days 2 and 10 after 9 Gy gamma ray irradiation. The TBA-RS contents in the liver on days 2 to 10 after irradiation were reduced by DMSO pretreatment. The irradiation decreased superoxide dismutase (SOD) activity in the liver on day 10. Decrease in SOD activity was prevented by DMSO pretreatment. In the electron microscopic study, the mitochondria in the irradiated mouse liver were swollen, but we could observe no change after DMSO pretreatment. The results suggest that DMSO has radioprotective effects, probably due to inhibition of lipid peroxidation.     

Change in lipid composition and lipid peroxidation rate in brain tissue under conditions of thymic hormone deficiency

Experiments on mature male rats have shown that 3 and 6 months after removal of the brain thymus, the level of total lipids in all cell centrifugate fractions (homogenate, supramitochondrial and mitochondrial fractions), which was followed by the higher rate of lipid peroxidation and the lower activity of cellular compartments, the spectrum imbalance of lipid fractions with predominant increases in the levels of phospholipids and free cholesterol. It is suggested that these changes make a contribution to the dysfunction of brain structures and participate in regulatory processes in thymectomy.     

The effect of linoleyl hydroxamic acid on lipid peroxidation processes and on the enzymatic activity of the antioxidant system in rats under hypoxia

It was studied the effect of new blocker of lipoxygenase way of arachidontic acid metabolism--linoleyl-hydroxamic acid--on the status of lipid peroxidation and antioxidant system in blood, heart, liver, lung and brain in rats under acute hypoxic hypoxia. It was shows that preliminary introduction of this substance lead to increase of antioxidant enzymes activity--superoxide dismutase and ceruloplasmine, and to decrease of lipid peroxidation level during hypoxia in blood, heart, liver and lung (without brain).     

The effect of the combined treatment of patients with postradiation encephalopathy on lipid peroxidation activity

Conventionally healthy persons-donors and diseased subjects who had taken part in the elimination of the Chernobyl accident effects were evaluated for the activity of the process of free radical lipid peroxidation (LPO). The patient population demonstrated a significant elevation of blood levels of malonic dialdehyde, enhancement of intensity of spontaneous chemoluminescence together with a decrease in resistance of red cells to oxide. After the general course of therapy involving use of enterosorbents, antioxidants, and normobaric intermittent hypoxia, there was an appreciable decrease in the blood plasma LPO intensity, which observation was accompanied with improvement in general health of the patients.     

Time-level relationship for lipid peroxidation and the protective effect of alpha-tocopherol in experimental mild and severe brain injury

OBJECTIVE: Oxygen free radical-mediated lipid peroxidation has been proposed to be one of the major mechanisms of secondary damage in traumatic brain injury. The first purpose of this study was to establish the time-level relationship for lipid peroxidation in injured brain tissue. The second purpose was to examine the protective effect of alpha-tocopherol against lipid peroxidation. METHODS: For this study, 65 guinea pigs in five groups were studied. Five of the animals were identified as a control group, and the remaining 60 animals were divided equally into four groups (Groups A, B, C, and D). Mild injury (200 g x cm) (Groups A and C) and severe injury (1000 g x cm) (Groups B and D) were produced by the method of Feeney et al. Alpha-tocopherol (100 mg/kg) was administered intraperitoneally before brain injury in Groups C and D. Five animals from each group were killed immediately after trauma, five after 1 hour, and the remaining five animals after 36 hours. Lipid peroxidation in traumatized brain tissues was assessed using the thiobarbituric acid method. RESULTS: In all groups with traumatic brain injuries, levels of malondialdehyde, a lipid peroxidation product, were higher than in the control group. The amount of lipid peroxidation was increased by the severity of the trauma. Alpha-tocopherol significantly suppressed the rise in lipid peroxide levels in traumatized brain tissues. CONCLUSION: This study demonstrates that lipid peroxidation is increased by the severity of trauma and that alpha-tocopherol has a protective effect against oxygen free radical-mediated lipid peroxidation in mild and severe brain injury.     

Differential expression of superoxide dismutase isoforms in neuronal and glial compartments in the course of excitotoxically mediated neurodegeneration: relation to oxidative and nitrergic stress

To examine the cellular distribution of radical scavenging enzymes in glia, in comparison to that in neurons and their behaviour during excitotoxically induced neurodegenerative processes, protein levels and the cellular localization of cytosolic and mitochondrial superoxide dismutase (Cu/Zn- and Mn-SOD) were investigated in the rat brain undergoing quinolinic acid (Quin)-induced neurodegeneration. Evidence for the specificity of the applied antibodies to detect immunocytochemically these SOD isoforms was obtained from electron microscopy and Western blotting. In control striatum Mn-SOD was clearly confined to neurons, whereas Cu/Zn-SOD was found, rather delicately, only in astrocytes. Microglia failed to stain with antibodies to both SOD isoforms. Quin application resulted in an initial formation of oxygen and nitrogen radicals as determined by the decline in the ratio of ascorbic to dehydroascorbic acid and by increased levels of nitrated proteins, an indicator for elevated peroxynitrite formation. Morphologically, massive neuronal damage was seen in parallel. Astroglia remained intact but showed initially decreased glutamine synthetase activities. The levels of Mn-SOD protein increased 2-fold 24 h after Quin injection (Western blotting) and declined only slowly over the time period considered (10 days). Cu/Zn-SOD levels increased only 1.3-fold. Immunocytochemical studies revealed that the increase in Mn-SOD is confined to neurons, whereas that of Cu/Zn-SOD was observed only in astroglial cells. Quiescent microglial cells were, as a rule, free of immunocytochemically detectable SOD, whereas in activated microglia a few Mn-SOD immunolabeled mitochondria occurred. Our results suggest a differential protective response in the Quin lesioned striatum in that Mn-SOD is upregulated in neurons and Cu/Zn-SOD in astroglia. Both SOD-isoforms are assumed to be induced to prevent oxidative and nitric oxide/peroxynitrite-mediated damage. In the border zone of the lesion core this strategy may contribute to resist the noxious stimulus.     

Changes in superoxide radical formation, lipid peroxidation, membrane fluidity and cathepsin B activity in aging and spawning male Chinook salmon (Oncorhynchus tschawytscha)

Superoxide radical (SOR) formation in the brain and the liver of male Chinook salmon (Oncorhynchus tschawytscha) increased in mitochondrial and plasma membrane samples as they aged. In 2-year-old salmon, spawning also lead to a significant elevation in SOR formation in mitochondrial and plasma membrane samples. The rise in this free radical was associated with an increase in lipid peroxidation, a decrease in plasma membrane fluidity, and an elevation in cathepsin B activity in the brain and liver. In 2-year-old spawning salmon, the changes in these parameters was greater than in 2-year-old non-spawning salmon. These observations suggest that free radical levels increase with aging and during spawning and indicate that these changes may be involved in cellular degeneration. In addition, these results support the suggestion that cellular degeneration accelerates during the spawning process.     

Effects of aluminum sulphate and citric acid ingestion on lipid peroxidation and on activities of superoxide dismutase and catalase in cerebral hemisphere and liver of developing young chicks

IgA antibodies reflecting airways or intestinal mucosal immune responses can be found in saliva and feces, respectively, and IgG antibodies reflecting serum antibodies can be found in saliva. In this study, antibodies were detected in samples of saliva and feces which had been air-dried at room temperature (+20 degrees C) or +37 degrees C, and stored at these temperatures for up to 6 months. In saliva the antibody levels increased, while the antibodies in feces decreased upon storage. The individual IgA antibody concentrations which were adjusted by using the ratios of specific IgA/total IgA were relatively stable in both saliva and feces, and correlated with corresponding antibody levels in samples which had been stored at -20 degrees C. The results indicate that air-dried saliva and feces can be used for semiquantitative measurements of mucosal antibodies, even after prolonged storage at high temperatures and lack of refrigeration.     

An experimental model of acute encephalopathy after total body irradiation in the rat: effect of liposome-entrapped Cu/Zn superoxide dismutase

PURPOSE: To develop an experimental model of acute encephalopathy following total body irradiation in rats and to define the therapeutic effect of liposome-entrapped Cu/Zn superoxide dismutase. METHODS AND MATERIALS: A total of 120 4-month-old rats received 4.5 Gy total body irradiation (TBI) while 120 rats received sham irradiation. A behavioral study based on a conditioning test of negative reinforcement, the one-way avoidance test, was performed 5 hours before irradiation and repeated the following days. Subcutaneous treatment was started 1 hour after irradiation and repeated daily for 2 weeks. In both the irradiated and sham group, three subgroups were defined according to the treatment received: liposome-entrapped Cu/Zn superoxide dismutase (0.5 mg/kg), liposomes only, normal saline. RESULTS: This work comprised two consecutive studies. In study A (90 rats) the one-way avoidance test was administered daily from day 0 to day 4 with a recall session at day 14. In study B (validation phase in 150 rats) the behavioral test was performed only from day 0 to day 6. Before irradiation, all rats showed a similar behavioral response. Study A (6 groups of 15 rats): Following TBI, irradiated rats treated with liposomes only or saline demonstrated a significant delay in learning the one-way avoidance test in comparison with sham-irradiated rats (0.05 < p <0.001 depending upon the day of evaluation and the subgroup type). In contrast, irradiated rats treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from sham-irradiated rats. Study B (6 groups of 25 rats): The results were the same as those in study A, demonstrating a significant delay in the learning of the test in the liposome and saline-treated irradiated rats in comparison with sham-irradiated rats (0.02 < p < 0.001). The irradiated rats, treated with liposome-entrapped Cu/Zn superoxide dismutase did not differ from the sham-irradiated controls. CONCLUSION: This study indicates that a relatively low dose of total body irradiation induces a substantial acute learning dysfunction in the rat. This effect is prevented by the administration of liposome-entrapped Cu/Zn superoxide dismutase.     

Preeclampsia, lipid peroxidation, and calcium adenosine triphosphatase activity of red blood cell ghosts

1. The effects of oxatriazole-type (GEA 3162 and GEA 5624) nitric oxide (NO) donors on mitogenesis and proliferation were studied in vascular smooth muscle cell (VSMC) culture. The effects of the GEA-compounds were compared with well-known NO-donors 3-morpholinosydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2. All NO-donors released NO and increased the production of cyclic GMP concentration-dependently. The production of cyclic GMP was inhibited by the guanylate cyclase inhibitor, ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one). 3. The NO-donors inhibited basal and serum-induced DNA synthesis concentration-dependently. The GEA-compounds were needed in concentrations 10 times lower than SIN-1 and SNAP. GEA 3162, SIN-1 and SNAP were also able to inhibit serum-induced cell proliferation. GEA 5624 was ineffective. The antimitogenic effect of NO-donors was not reduced by inhibiting the guanylate cyclase. 4. These results suggest that NO inhibits serum-induced DNA synthesis and proliferation of VSMC by a cyclic GMP-independent mechanism. The oxatriazole-type NO-donor GEA 3162 was found to be a more potent inhibitor of mitogenesis and cell proliferation than SIN-1 and SNAP.     

Changes in the intensity of lipid peroxidation in the blood plasma of sheep under repeat gamma irradiation after chronic gamma exposure]

OBJECTIVES: To measure the long term effects of dance training and the contribution of the timing and duration of any menstrual disruption on bone mineral density (BMD). DESIGN: Measurement of BMD in 57 premenopausal, previously professionally dance trained women and the relationship to menstrual and training history. MAIN OUTCOME MEASURES: Bone density measurements at lumbar spine and femoral neck by dual energy x-ray absorptiometry. RESULTS: The average Z score for BMD at the lumbar spine in the amenorrhoeic dancers was significantly below that for the normal population. The average Z score for BMD at the femoral neck in the eumenorrhoeic dancers was significantly above that for the normal population. There was a significant difference between the average Z score for BMD at both the lumbar spine and femoral neck between the amenorrhoeic and eumenorrhoeic dancers. Significant negative relationships were found between BMD at the lumbar spine and (1) age at menarche, (2) duration of amenorrhoea, (3) BMD at the femoral neck, and (4) the variable of ideal minus lowest weight, which was independent of amenorrhoea. No significant relationships were found between duration of oral contraceptive pill usage and BMD at either the lumbar spine or the femoral neck in eumenorrhoeic or amenorrhoeic dancers. In order to quantify the effect of a combination of these significant factors, a model of BMD was constructed using multiple regression incorporating the variables duration of amenorrhoea, age at menarche, and ideal minus lowest body weight. In this model R2 was 33.6%, in other words 33.6% of the total variation in the Z score for BMD at the lumbar spine could be accounted for by these factors. CONCLUSION: Professional female dancers with a history of delayed menarche and amenorrhoea have been identified as another group of premenopausal women potentially at risk of developing osteoporosis because of a decrease in BMD at the lumbar spine. The femoral neck in dancers with a history of amenorrhoea was partially protected from loss of BMD by virtue of being the major weight bearing site in previous dance training, and in eumenorrhoeic dancers BMD was significantly increased at this site.     

Free radical-mediated tissue injury in acute lung allograft rejection and the effect of superoxide dismutase

BACKGROUND: The role of monocytes and neutrophils is crucial during acute allograft rejection. They have the capacity to generate toxic reactive oxygen intermediates in response to specific agonists that may act as tissue destructive molecules. We examined the possibility of reactive intermediate-mediated tissue injury in acute lung allograft rejection, as well as the effect of superoxide dismutase. METHODS: Allogenic (Brown Norway to F344) or syngenic (F344 to F344) rat left-lung transplantation was performed. Generation of reactive oxygen intermediates in peripheral blood was evaluated by the method of luminol-dependent chemiluminescence. Cell membrane phospholipid peroxidation in the graft was measured as malondialdehyde concentration. The third group of animals having allografts received bovine erythrocyte superoxide dismutase (5,000 U/kg intravenously every 12 hours after transplantation). RESULTS: Relative chemiluminescence response in the allograft recipient to normal F344 was elevated on postoperative day 1 (257%), then decreased slightly on day 3 (156%) and was elevated again on day 7 (560%) as the process of rejection progressed. Allograft tissue malondialdehyde levels (248.37 +/- 112.35 nM/whole lung, n = 6; p < 0.05 by Student's t test) were higher than isograft levels (139.29 +/- 35.93 nM/whole lung, n = 6) on day 7. Superoxide dismutase treatment significantly ameliorated the histologic degree of rejection on day 7. CONCLUSIONS: These results demonstrate the tissue destructive activity of reactive oxygen intermediates during lung allograft rejection. To scavenge free radicals may be a useful therapeutic modality in the management of acute lung allograft rejection.     

The typological characteristics of the stress activation of lipid peroxidation and its correction by thymopentin

On the model of acute stress in rats the dependence of accumulating of peroxide hydrogen from typological peculiarities of organism was determined. The highest level of activation of lipid peroxide oxidation coincides with maximally expressed impairing of stomach mucous membrane the dependence of processes of lipid peroxide oxidation in stress from typological peculiarities of organism was grounded as well as high effectiveness of correction of ulcerogenic effects by neuropeptide thymopentin.