Progesterone protects against lipid peroxidation following traumatic brain injury in rats

Large scale use of lysozyme for periplasmic release has been impeded by the cost of the pure enzyme and its subsequent presence as a contaminant in later downstream processing steps. In this paper, we discuss the use of lysozyme for pilot scale recovery of a periplasmic enzyme from E. coli. The effects of concentration of sucrose, lysozyme and cells on periplasmic enzyme release were examined. Lysozyme concentration can be reduced 5-fold from previous reports and a reduction in sucrose concentration from 20 to 15% (w/v) allows an improvement in centrifugal harvesting by reducing viscosity. High levels of release were still achieved using this technique and further improvements in yield were obtained by optimising other components of the releasing mixture. Results show that some release is still achieved in circumstances where no lysozyme use is possible. Results also indicate that a substantial proportion (up to 70%) of lysozyme remains bound to the cellular debris after its action and is removed with this material.     

Ischemic tolerance and lipid peroxidation in the brain

Using a modified method of focal ischemic preconditioning (FIP) followed by permanent middle cerebral artery occlusion (MCAO), we studied the effects of ischemic tolerance on infarct volume. The FIP was achieved by obstructing the blood flow into the MCA using miniature clamps at two points simultaneously. The first point was proximal to its origin and the second was where it intersects the middle cerebral vein. In rats subjected to three short conditioning periods (3 x 3 min with 7 min reperfusion between occlusions), there were significant reductions in the infarct volume in the cerebral cortex induced by the subsequent MCAO in FIP-treated rats compared with sham-operated controls. This rapid FIP-induced ischemic tolerance to subsequent MCAO occurred within 1 day and lasted for 5 days. Tissue lipid peroxidation in the cortex was significantly reduced for up to 2 days after FIP. In contrast, lipid peroxidation increased rapidly after MCAO. A significant reduction in this increase was observed in FIP-treated rats, suggesting a correlation with the subsequent reduction in the infarct volume.     

The relationship between sexual abuse and mild traumatic brain injury

It remains unclear why some individuals with mild traumatic brain injury (MTBI) complain of cognitive deficits many months after the injury. Given neuropathological changes associated with prolonged stress, such as occurs with repeated sexual abuse (SA), it seems possible that individuals who experienced SA might be predisposed to greater deficits after MTBI. Four groups of subjects were administered measures of cognitive and emotional functioning. These groups were those with MTBI (n = 10), those with a history of SA (n = 10), those with both MTBI and SA (n = 10), and normal control (NC) subjects (n = 10). Compared to the NC subjects, those with MTBI demonstrated deficits in working memory, those with SA demonstrated deficits in executive functioning, and those with both MTBI and SA demonstrated the greatest number of deficits which were in working memory, executive functioning and memory. Tests of anxiety, depression and post-traumatic stress disorder, while demonstrating significant symptoms in all clinical groups, did not correlate with the neuropsychological tests that differentiated the groups.     

The protective role of plasmalogens in iron-induced lipid peroxidation

The role of plasmalogens in iron-induced lipid peroxidation was investigated in two liposomal systems. The first consisted of total brain phospholipids with and without plasmalogens, and the second of phosphatidylethanolamine/phosphatidylcholine liposomes with either diacyl- or alkenylacyl-phosphatidylethanolamine. By measuring thiobarbituric acid reactive substances, oxygen consumption, fatty acids and aldehydes, we show that plasmalogens effectively protect polyunsaturated fatty acids from oxidative damage, and that the vinyl ether function of plasmalogens is consumed simultaneously. Furthermore, the lack of lag phase, the increased antioxidant efficiency with time, and the experiments with lipid- and water-soluble azo compounds, indicate that plasmalogens probably interfere with the propagation rather than the initiation of lipid peroxidation, and that the antioxidative effect cannot be related to iron chelation.     

Effect of alpha-tocopherol on lipid peroxidation and total antioxidant status in spontaneously hypertensive rats

The aim of this study was to determine the effects of alpha-tocopherol on lipid peroxidation and total antioxidant status of spontaneously hypertensive rats (SHR), comparing them with normal Wistar-Kyoto (WKY) rats. SHR were divided into three groups and treated with different doses of alpha-tocopherol (alpha1, 17 mg/kg diet; alpha2, 34 mg/kg diet; and alpha3, 170 mg/kg diet). Normal WKY and untreated SHR were used as normal (N) and hypertensive control (HC). Blood pressures were recorded every 10 days for 3 months. At the end of the trial, animals were killed and measurement of plasma total antioxidant status, plasma superoxide dismutase (SOD) activity, and lipid peroxide levels in plasma and blood vessels was carried out following well-established methods. From our study it was found that lipid peroxides in thoracic aorta (N, 0.47 +/- 0.17; H, 0.96 +/- 0.37; P < .0001) and plasma (N, 0.06 +/- 0.01; H, 0.13 +/- 0.01) were significantly higher in hypertensives than in normal rats. SOD activity was significantly lower in hypertensive than normal rats (N, 172.93 +/- 46.91; H, 110.08 +/- 14.38; P < .005). Total antioxidant status was significantly higher in normal than hypertensive rats (N, 0.88 +/- 0.05; H, 0.83 +/- 0.02; P < .05). After the antioxidant trial, it was found that in the treated groups rise of blood pressure was prevented significantly (P < .001) and lipid peroxides in blood vessels were significantly reduced more than in the controls (P < .001). For plasma lipid peroxide it was only significant for groups alpha2 (P < .001) and alpha3 (P < .05). Although all three treated groups showed improved total antioxidant status, only groups alpha2 (0.87 +/- 0.04, P < .005) and alpha3 (1.20 +/- 0.18, P < .001) were statistically significant. All the three groups showed significant increases in their SOD activity (P < .001). Correlation studies showed that total antioxidant status and SOD were significantly negatively correlated with blood pressure in normal rats (P = .007; P = .008). Lipid peroxides in both blood vessel and plasma showed a positive correlation. In the treated groups, lipid peroxides in blood vessels maintained a significant positive correlation with blood pressure in all groups (alpha1, P = .021; alpha2, P = .019; alpha3, P = .002), whereas for plasma lipid peroxides the correlation was in groups alpha1 (P = .005) and alpha2 (P = .009). For SOD activity, significant negative correlations were found with blood pressure in the alpha2 (P = .017) and alpha3 (P = .025) groups. Total antioxidant status maintained a significant negative correlation with blood pressure in all three groups (alpha1, P = .012; alpha2, P = .044; alpha3, P = .014). In conclusion it was found that supplement of alpha-tocopherol may prevent development of increased blood pressure, reduce lipid peroxides in plasma and blood vessels, and enhance the total antioxidant status, including SOD activity.     

Rate constants for quenching singlet oxygen and activities for inhibiting lipid peroxidation of carotenoids and alpha-tocopherol in liposomes

BACKGROUND: Familial juvenile polyposis (JP) is an autosomal dominant condition in which affected individuals develop upper or lower gastrointestinal (GI) juvenile polyps, or both, and have a predisposition to cancer of the gastrointestinal tract. The risk of GI cancer has not been well defined because of the small number of these families and the lack of follow-up. The objective of this study was to determine the prevalence and age at diagnosis of GI polyposis and cancer in a large JP kindred. METHODS: Medical records were reviewed, patients were interviewed, and histories were taken. Pathology reports and slides were reviewed by our pathologists. A database was created for analysis of clinical and pathologic factors. RESULTS: This kindred contains 117 members, 29 of whom have had upper or lower GI polyps or cancer, or both. All those affected have had colonic juvenile polyps or cancer, except for two who died of advanced gastric cancer and never had colonic evaluation. Nine individuals have had both upper and lower GI polyps or cancer. Sixteen of 29 (55%) affected patients have developed gastrointestinal cancer. Eleven (38%) have had colon cancer, and six (21%) have had upper GI cancers. CONCLUSIONS: The risk of gastrointestinal malignancy in affected members of this JP kindred exceeds 50%. The high risk of GI cancer warrants frequent endoscopic screening of both affected and at-risk family members. Screening will soon be facilitated by presymptomatic genetic testing for the identification of gene carriers.     

Effect of alpha-tocopherol succinate on free radical and lipid peroxidation levels in BL6 melanoma cells

Numerous studies have proposed a radical or oxidant involvement in a number of degenerative diseases such as cancer. This has led to suggestions that the supplementation of antioxidants such as alpha-tocopherol (vitamin E) may function to reduce the growth of cancer. In this study, a nonmalignant Monkey kidney (LLCMK) and a malignant Murine melanoma (BL6-F10) cell line were supplemented with varying levels of alpha-Tocopherol acid succinate (vitamin E succinate) ranging from 1 to 10 microg/ml. BL6-F10 cells supplemented with 5, 7, and 10 microg/ml vitamin E succinate, showed significant decreases in cell proliferation, and this decrease was accompanied by a concomitant increase rather than a decrease in the levels of free radicals and lipid peroxidation. LLCMK cells supplemented with 1-10 microg/ml vitamin E succinate showed no significant increase or decrease in growth, while the levels of lipid peroxidation were shown to be insignificantly elevated at 5, 7, and 10 microg/ml vitamin E succinate. Free radical levels in LLCMK cells were significantly decreased at 1 microg/ml vitamin E succinate, while at 3, 5, 7, and 10 microg/ml supplementary vitamin E succinate, free radical levels increased compared to the 1 microg/ml group, but not compared to control cultures. These results suggest that the inhibitory effects of vitamin E succinate on BL6-F10 cell growth in vitro is not a consequence of its antioxidant properties, but may, in fact, be due to one or more of its other potential roles within the cells, such as the regulation of cellular enzyme activities involved in growth.     

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.     

beta-Carotene accumulation in mouse tissues and a protective role against lipid peroxidation

Recent population-based efficacy trials of the synthetic malaria vaccine SPf66 have shown restricted, if any, clinical protection against Plasmodium falciparum infection. Despite the well-established role of antibodies in effector responses against asexual blood-stage malaria parasites, the titres of anti-SPf66 IgG antibodies do not correlate with the ability of sera from vaccine recipients to inhibit parasite growth in vitro nor with partial clinical protection which could be detected in some trials. Qualitative or functional parameters of SP66-induced antibody responses, such as IgG subclass composition and affinity, may be more predictive of clinical protection against malaria than quantitative estimates of antibody concentration or titre. Since these parameters are readily estimated by laboratory techniques currently available, and may be modulated by changes in vaccination protocols and by the use of different adjuvants, a better understanding of qualitative antibody responses induced by SPf66 and other asexual blood-stage malaria vaccine candidates, and of their relationship with clinical protection in vivo, is urgently needed for the improvement of currently used immunization schedules.     

The protective effect of metallothionein against lipid peroxidation caused by retinoic acid in human breast cancer cells

The treatment of breast cancer by retinoic acid (RA) may be mediated by lipid peroxidation. Expression of metallothionein (MT) in cancer cells, however, can protect against lipid peroxidation by scavenging hydroxyl radicals. In this study, a two-by-six factorial design was used to investigate the interactive effects of all-trans-RA and zinc (Zn)-induced MT on the growth of two human breast cancer cell lines differing in basal expression of MT and estrogen receptors; MCF7 cells express estrogen receptor, BT-20 cells do not. Cells were treated with Zn to induce MT and then treated with six RA concentrations. Cell proliferation, lipid peroxidation, MT protein, MT mRNA and glutathione concentrations were measured. BT-20 cells expressed higher constitutive MT concentrations than MCF7 cells. MT was significantly increased by Zn treatment in BT-20 cells but not in MCF7 cells. Low RA concentrations stimulated growth proliferation but higher concentrations inhibited cell proliferation. Elevated RA concentrations increased lipid peroxidation as measured by thiobarbituric acid reactive substances. There was a significant negative correlation between lipid peroxidation and cell proliferation. Growth inhibition and lipid peroxidation were reduced by Zn pretreatment in BT-20 cells but not in MCF7 cells. RA increased MT levels in both cell lines, which suggests that RA may generate free radicals which will induce MT mRNA expression. Glutathione did not appear to be a significant factor. Therefore, induction of MT by Zn may modulate the growth inhibitory effects of RA in human breast cancer cells. One mechanism of growth inhibition may be through increased lipid peroxidation. Induction of MT by RA may be one explanation for acquired RA resistance in cancer.     

The relationship between lipid peroxidation and life span in Drosophila melanogaster

Using Drosophila lines pre-selected for adaptive characters, studies have been made on the relationship between the intensity of lipid peroxidation and life span in flies of different genotype, age and physiological condition. It was shown that the intensity of lipid peroxidation depends mainly on different factors (sex, age, virginity) in different lines. No expected negative correlation was found between the level of lipid peroxidation and life span in hybrids between two inbred lines. The intensity of lipid peroxidation was inherited like a dominant character, the dynamics of aging--like a codominant one in females and superdominant in males. Both the level of lipid peroxidation and life span appeared to be sex-dependent characters.     

The effect of alpha-1-acidic glycoprotein on neutrophil chemiluminescence and lipid peroxidation in experimental thermal trauma

Induced chemoluminescence of neutrophils was distinctly inhibited both in intact mice and the animals with thermal injury after administration of acid alpha 1-glycoprotein. At the same time, the glycoprotein decreased the rate of thermal burn-induced activation of lipid peroxidation in rat blood, skin and liver tissue. Antioxidative and therapeutic effects of acid alpha 1-glycoprotein in burns appear to be related to regulation of neutrophil activity.     

The induction of lipid peroxidation in human brain glial tumors

Tissue examinations of glial tumors in the human brain revealed that therein lipid peroxidation could be induced by using bivalent iron salts, which is indicated by higher malonic dialdehyde levels. The authors have demonstrated that the glioma tissue levels of iron were statistically lower than those in the brain tissue. The induction in tumor tissue does not depend upon the degree of its malignancy, but it significantly differs from this parameter in the rabbit brain tissue. The induction of lipid peroxidation processes is accompanied by a lower cumulative antioxidative activity. The findings open new prospects for affecting tumor growth.     

Oxidation of alpha-tocopherol during the peroxidation of dilinoleoylphosphatidylcholine in liposomes

Liposomal suspensions of dilinoleoylphosphatidylcholine (DLPC) containing alpha-tocopherol (0.1 mol%, based on DLPC were oxidized at 37 degrees C. The oxidation was initiated by a lipid-soluble or water-soluble free radical initiator, or by the addition of CuSO4 and fructose. In all the oxidation systems, alpha-tocopherol suppressed the formation of DLPC hydroperoxides until all the alpha-tocopherol had been depleted. The oxidation products of alpha-tocopherol were 8a-alkyldioxy-alpha-tocopherones, 5,6-epoxy-alpha-tocopherylquinone, 2,3-epoxy-alpha-tocopherylquinone, and alpha-tocopherylquinone. The 8a-alkyldioxy-alpha-tocopherones were decomposed in the liposomes primarily by being hydrolyzed to produce alpha-tocopherylquinone. The results indicate that alpha-tocopherol can trap peroxyl radical to form 8a-alkyldioxy-alpha-tocopherones which are hydrolyzed to alpha-tocopherylquinone in phospholipid bilayers. In another oxidation pathway, alpha-tocopherol may be oxidized by peroxyl radicals to form isomeric epoxy-alpha-tocopherylquinones.     

Protective effect of dehydroepiandrosterone against copper-induced lipid peroxidation in the rat

This study investigates the effectiveness and multitargeted activity of dehydroepiandrosterone (DHEA) as antioxidant in vivo. A single dose of DHEA was given IP to male rats. Liver and brain microsomes, and plasma low density lipoprotein (LDL), were isolated from rats sacrificed 17 h later. Liver and brain microsomes were challenged with CuSO(4) and, as index of lipid peroxidation, the production of thiobarbituric acid reactive substances (TBARS) was measaured. Also, plasma low-density lipoprotein (LDL) were challenged with copper and the time course of lipid peroxidation was evaluated following the formation of conjugated dienes. The onset of TBARS generation induced by copper was marked delayed in both liver and brain microsomes from DHEA-treated animals. Also, the resistance of LDL to oxidation, expressed by the duration of the lag-phase of the kinetic curve, was significantly enhanced in DHEA-treated rats. Results indicate that in vivo DHEA supplementation makes subcellular fractions isolated from different tissues and plasma constituents (LDL) more resistant to lipid peroxidation triggered by copper. The antioxidant effect on plasma LDL might be of special relevance to the proposed antiatherogenic activity of DHEA. Moreover, multitargeted antioxidant activity of DHEA might protect tissues from oxygen radicals damage.     

Dynamics of lipid peroxidation and antioxidant system in patients with severe combined trauma

The objective of the study was to determine the influence of blood loss volume on lipid peroxidation (LP) process and antioxidant system (AOS) state in the patients with a heavy combined trauma. The studies were proceeded in 36 patients with a heavy combined trauma. The mean age of the patients was 40 +/- 2. A craniocerebral trauma was associated with trauma of both thorax and abdominal cavities and locomotor system. Blood loss reached 75% of circulating blood volume (CBV), mean value was 28 +/- 3%. Blood samples for the studies were obtained at admission of the patients by emergency medical service teams, and--after 4; 24 hours, 3 and 7 days after the trauma. CBV determination was made by dradioisotope method. LP and AOS state was judged from serum level of primary (conjugated dienes), secondary (malonic dialdehyde, MDA) LP products and extracellular antioxidant enzyme ceruloplasmin (CP). K coefficient, an integral indicator was used for LP-AOS system imbalance assessment. According to the obtained data, in the studied patients intensification of the LP processes manifesting in CD and MDA contents increase was most expressed from 1 to 3 days after trauma (2.0-2.6-fold, p < 0.05) and rise of TP content maximally in the 3 day 2.28-fold (p < 0.05) was observed in the there patients. At the admission of decrease (1.6-fold, p < 0.05) was registered which normalized to the 3 day. K coefficient time course study permitted to establish that as early as at the admission of the patients into the clinic its value was substantially higher than the normal one, and to the 4 hour the imbalance in the LP-AOS system increased 5.0-fold (p < 0.05). An expression of LP processes and AOS disturbances in the patients with heavy combined trauma depended on the blood loss volume. The revealed imbalance in the LP-AOS system is indicative of a necessity of inclusion antioxidants into the complex therapy.     

The effect of exercise intensity on lipid peroxidation

This study characterizes exercise-induced lipid peroxidation during graded aerobic exercise in seven healthy men and women (36.4 +/- 3 yr). Levels of ethane and pentane in expired breath during cardiopulmonary exercise stress testing were measured at rest, lactic acidosis threshold (LAT), maximal exercise (VO2max), and recovery. Serum malonaldehyde (MDA) levels were measured at rest before exercise and 5 min after maximal exercise. Expired ethane and pentane flux levels were increased above resting levels at LAT, continued to rise at VO2max, then declined during recovery. Serum MDA levels were not significantly different before and after maximal exercise. Substantial exercise-induced lipid peroxidation (by expired ethane and pentane) apparently occurred in healthy individuals at LAT and continued to increase at VO2max, yet rapidly attenuated during post-exercise recovery. These findings indicate that in healthy individuals physical exercise induced lipid peroxidation transiently and that there was a removal of lipid peroxidation byproducts during recovery.     

Sensitivity of ATPase-ADPase activities from synaptic plasma membranes of rat forebrain to lipid peroxidation in vitro and the protective effect of vitamin E

The in vitro effects of membrane lipid peroxidation on ATPase-ADPase activities in synaptic plasma membranes from rat forebrain were investigated. Treatment of synaptic plasma membranes with an oxidant generating system (H(2)0(2)/Fe(2+)/ascorbate) resulted in lipid peroxidation and inhibition of the enzyme activity. Besides, trolox as a water soluble vitamin E analogue totally prevented lipid peroxidation and the inhibition of enzyme activity. These results demonstrate the susceptibility of ATPase-ADPase activities of synaptic plasma membranes to free radicals and suggest that the protective effect against lipid peroxidation by trolox prevents the inhibition of enzyme activity. Thus, inhibition of ATPase-ADPase activities of synaptic plasma membranes in cerebral oxidative stress probably is related to lipid peroxidation in the brain.     

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.