thiobarbituric-acid and Brain-Ischemia

Oxidative stress associated with chronic cerebral hypoperfusion is one of the fundamental factors leading to neurodegenerative diseases. To prevent oxidative stress, physical activity is effective. Physical exercise enables development of rehabilitation techniques that can progressively increase patients' stress resistance. We determined the oxidative stress dynamics in experimental hypoperfusion and modeled rehabilitation measures, comparing sex and stress resistance levels. The experiment was performed on 240 Wistar rats of both sexes over a period of 90 days. Based on behavioral test results obtained using the open field test, the rats were divided into active animals with predicted higher stress resistance (HSR) and passive animals with predicted lower stress resistance (LSR). TBA (thiobarbituric acid) plasma concentration of the active products (malondialdehyde-MDA), blood plasma (NO-X) concentration, and L-citrulline (LC) concentration were determined spectrophotometrically at the corresponding wave length (nm). The intensity of oxidative stress was evaluated using the chemoluminscent method to determine the blood plasma antioxidant activity on the BCL-07 biochemoluminometer. This study revealed two stages of oxidative stress: a less pronounced phase covering the first days after surgery and a main one, which starts from the month after the operation to 3 months. Female sex and a high initial level of stress resistance reduced the severity of oxidative stress. Physical activity commencing a week after the surgery resulted in "reloading" the adaptive mechanisms and slowed the onset of the main stage, leading to a decrease in the free-radical process in all studied subgroups and the greater blood plasma (NO)-X decrease in the male animals. Future neuropharmacological intervention most likely will be able to determine the pathophysiology mechanism of chronic brain hypoperfusion and potentially extending adaptive responses.

Topics: Animals; Brain; Brain Ischemia; Female; Male; Malondialdehyde; Maze Learning; Oxidative Stress; Physical Conditioning, Animal; Rats, Wistar; Sex Factors; Stress, Psychological; Thiobarbiturates

Lipid peroxidation was studied in the brain of Mongolian gerbils under conditions of complete ischemia followed by recirculation in the left hemisphere without recirculation in the right hemisphere. Thiobarbituric acid reactive products and the intensity of Fe2+-induced chemiluminescence were determined. The content of lipid peroxidation products in the brain tissue was increased not only under conditions of recirculation, but also at the ischemia stage during the limited access of oxygen. Thus, the destructive effect of free radicals may occur even during the early stage of ischemic injury of the brain.

Topics: Animals; Antioxidants; Brain; Brain Ischemia; Butylated Hydroxytoluene; Disease Models, Animal; Female; Gerbillinae; Lipid Peroxidation; Luminescent Measurements; Male; Reperfusion; Thiobarbiturates

Non-insulin-dependent diabetes mellitus (NIDDM) and hyperhomocysteinemia are both associated with increased lipid peroxidation (oxidative stress). This may contribute to the accelerated vascular disease associated with these conditions. It is not known whether the coexistence of elevated homocysteine levels will stimulate oxidative stress further than that caused by diabetes alone.. Plasma concentrations of thiobarbituric acid reactive substances (TBARS), an index of lipid peroxidation, were measured in patients with NIDDM who had previously had a methionine load test; some of the patients had hyperhomocysteinemia.. Plasma TBARS concentrations were elevated in diabetics with vascular disease. The additional presence of hyperhomocysteinemia was not associated with a further increase in plasma TBARS concentrations.. Lipid peroxidation is increased in patients with diabetes mellitus and macrovascular disease and is not further elevated by the coexistence of elevated homocysteine levels. It is possible that diabetes maximally stimulates oxidative stress and any further acceleration of vascular disease in patients who have coexistent hyperhomocysteinemia is mediated through mechanisms other than lipid peroxidation.

Topics: Adult; Analysis of Variance; Brain Ischemia; Carotid Artery Diseases; Case-Control Studies; Coronary Disease; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Free Radicals; Homocysteine; Humans; Hypoglycemic Agents; Insulin; Lipid Peroxidation; Male; Methionine; Middle Aged; Oxidative Stress; Peripheral Vascular Diseases; Sulfonylurea Compounds; Thiobarbiturates

The inhibition of lipid peroxidation by oligomeric derivatives synthesized from prostaglandin E1 (PGE1) and PGB2 was studied using two rat models. In an in vitro model, the brain was exposed to decapitation-ischemia, the cortex was removed and homogenized, and the formation of thiobarbituric acid reactive substances (TBAR) was measured after exposing the homogenate to in vitro reoxygenation either in the presence or absence of oligomers. It was found that these oligomers could inhibit lipid peroxidation, and that their activities were higher than that of superoxide dismutase (SOD). In an in vivo administration model, either the oligomer or the vehicle was injected i.p. 30 min before decapitation. The brain was exposed to decapitation-ischemia, the cortex was homogenized and exposed to 'in vitro' reoxygenation, after which TBAR value was determined. Ester-type compounds had a greater activity than free-acid type compounds in inhibiting lipid peroxidation. A possible mechanism of the protective effect of these oligomers in ischemia/reperfusion injury may be to scavenge oxygen free radicals.

Topics: Alprostadil; Animals; Antioxidants; Brain Ischemia; Cerebral Cortex; Electron Spin Resonance Spectroscopy; Free Radicals; In Vitro Techniques; Lipid Peroxidation; Macromolecular Substances; Prostaglandins B; Rats; Thiobarbiturates

Extracellular free radicals were detected in rat striatal perfusate samples by intracerebral microdialysis coupled to the spin trapping technique. Five Sprague-Dawley rats were subjected to 30 min of global ischemia followed by reperfusion; throughout the experimental period the intrastriatal dialysing probe was perfused with Ringer's solution containing the spin trap agent pyridyl-N-oxide-t-butylnitrone (100 mM) together with the iron chelating agent diethylentriaminepentacetic acid (100 microM). A radical adduct occurred during ischemia and early reperfusion, but not in basal conditions; the spin adduct was characterized as a carbon centered radical, consistent with the presence of an oxidative attack on membrane lipids. The direct evidence of the formation of free radicals supports the hypothesis that free radicals play a role in the pathogenesis of the histological damage during brain ischemia.

Topics: Animals; Brain Ischemia; Cyclic N-Oxides; Dialysis; Free Radicals; Nitrogen Oxides; Pyridines; Rats; Rats, Inbred Strains; Reperfusion; Spin Labels; Thiobarbiturates

The ability of stobadine (ST) to prevent lipid peroxidation was tested in incomplete rat cerebral ischemia induced by 4 hour ligation of the common carotid arteries with a subsequent 10 min reperfusion. The extent of lipid peroxidation was determined by the measurement of the level of conjugated dienes (CD) and thiobarbituric acid reactive substances (TBARS). The levels of CD and TBARS were significantly elevated in brain cortex samples from animals subjected to ischemia followed by reoxygenation in comparison with ischemic samples without reperfusion, samples from sham operated or control animals. The concentration of CD and TBARS significantly decreased in animals treated with therapeutic doses of ST (2 mg/kg) administered i.v. immediately before reperfusion or 10 min after the onset of reperfusion. Stobadine was more effective than the known lipid antioxidant vitamin E, given in a dose of 30 mg/kg.day i.m. over 3 consecutive days prior to ischemia. The beneficial effect of ST on survival of rats was more effective in comparison with vitamin E. Significant changes were found in the activities of the antioxidative enzymes, i.e. increase in superoxide dismutase (SOD) and decrease in glutathione peroxidase (GP) in brain cortex samples from animals subjected to ischemia followed by reoxygenation. Stobadine prevented these changes. Catalase (CAT) activity was not detectable. It may be concluded from the increased SOD activity that oxygen radicals play a significant role in cerebral ischemia followed reperfusion. In addition to its antioxidant effect, stobadine probably prevents superoxide radical generation. The mechanism of xanthine oxidase inhibition is not involved in preventing superoxide radical generation by stobadine. Stobadine maintained high GP activity, probably by preventing glutathione oxidation.

Topics: Animals; Antioxidants; Brain; Brain Ischemia; Carbolines; Lipid Peroxidation; Male; Rats; Rats, Inbred Strains; Reperfusion; Thiobarbiturates; Vitamin E

Several feasible mechanisms have been proposed as sources of neuronal damage from ischemia and subsequent reperfusion. Included among these are oxidative damage caused by free radical production and lipid peroxidation and products derived from phospholipid breakdown. A series of 4-thiazolidinone compounds represented by LY178002 (5-[3,5-bis(1,1-dimethylethyl)-4-hydroxyphenyl]methylene-4-thiazolidinon e) have been described as inhibitors of multiple enzymes in the arachidonic acid cascade, including fatty acid cyclooxygenase, 5-lipoxygenase, and phospholipase A2. Accordingly, we evaluated LY178002 in a four-vessel occlusion model of global forebrain ischemia with reperfusion. A 2-hour pretreatment of 11 male Wistar rats with 150 mg/kg LY178002 significantly protected against striatal (p = 0.0007) and hippocampal CA1 (p = 0.006) damage after 30 minutes of global ischemia. Similar protection was observed for the striatum (p = 0.005) and hippocampal CA1 layer (p = 0.025) after pretreatment of 13 rats with 50 mg/kg LY178002. We further evaluated LY178002 as a possible inhibitor of lipid peroxidation because part of its chemical structure incorporates the aromatic backbone of the known antioxidant butylated hydroxytoluene. We found LY178002 to be a potent inhibitor of iron-dependent lipid peroxidation. Few substances possessing a single pharmacological activity have been found to be of significant therapeutic benefit in global ischemia of 30 minutes' duration because the mechanisms that lead to cell death in response to ischemia are likely to be multifactorial. Thus, the efficacy of LY178002 in this model may be due to its ability to inhibit multiple sources of damage.

Topics: Animals; Brain; Brain Ischemia; Corpus Striatum; Ferritins; Hippocampus; Iron; Male; Methemoglobin; Phospholipases A; Phospholipases A2; Rats; Rats, Inbred Strains; Thiazoles; Thiazolidines; Thiobarbiturates

The effect of ischemia on the properties of 5-hydroxytryptamine1A + B (5-HT1A+B) and 5-hydroxytryptamine1B (5-HT1B) binding sites, physical-state "fluidity" of the membrane, and its susceptibility to peroxidation in vitro was investigated in the cerebral cortex of gerbils. Ischemia was induced by bilateral carotid artery occlusion for 15 min alone or with release for 1 h. Ischemia both with and without reflow decreased the number of 5-HT1A + B and 5-HT1B binding sites, whereas ischemia and reflow altered the affinity for 5-HT1B binding sites. Resistance to the temperature-dependent increase in "fluidity" of the membrane was detected (by fluorescence anisotropy using 1,6-diphenyl-1,3,5-hexatriene as a probe) after ischemia and reflow but not in ischemia alone. Susceptibility of the membranes to Fe2+- and ascorbic acid-stimulated lipid peroxidation in vitro was decreased following ischemia and recirculation only. These findings strongly suggest that the composition and the function of the membrane are markedly disturbed during recirculation after ischemia.

Topics: Animals; Brain Ischemia; Cerebral Cortex; Gerbillinae; Lipid Peroxides; Membrane Fluidity; Membranes; Receptors, Serotonin; Serotonin; Thiobarbiturates