Serpiginous choroidopathy presenting as choroidal neovascularisation.
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Adult↗
Biomedical subjects
W Augustin
Publications and source records attributed to W Augustin.
Oxidative stress in cardio renal anemia syndrome: correlations and therapeutic possibilities.
Cardiovascular injury has been shown to be the most critical factor affecting quality of life and mortality in patients suffering from chronic renal failure. Oxidative stress has been thought to be an important risk factor for cardiovascular disorders. As oxidative stress parameters with high cardiovascular risk factor 4-hydroxynonenal and other aldehydic lipid peroxidation products, F2-isoprostanes, homocysteine, and cholesterol oxidation products were measured in chronic renal failure patients. 4-Hydroxynonenal and some cholesterol oxidation products correlated well with the degree of renal anemia. F2-isoprostane levels were related to inflammation, whereas homocysteine was increased due to malnutrition. Further, cholesterol oxidation products correlated well with the consumption of lipophilic antioxidants such as alpha-tocopherol. There was an almost linear correlation between the left ventricular mass index and 4-hydroxynonenal. Both parameters furthermore showed an inverse relationship to hemoglobin concentration. The correction of renal anemia by means of erythropoietin therapy led to an efficient strengthening of the antioxidative defence system. The improvement of the antioxidative capacity is of complex nature comprising both enzymatic pathways and low molecular antioxidants. The correction of renal anemia with its well documented reduction of the cardiovascular risk can be regarded as an antioxidative therapy, demonstrating the clinical efficiency of antioxidative protection in patients with chronic renal failure.
Anemia↗
Oxidative stress in chronic renal failure as a cardiovascular risk factor.
Myocardial injury has been shown to be the most critical factor influencing quality of life and mortality in patients with chronic renal failure. Oxidative stress has been postulated to be an important risk factor for cardiovascular disorders. One reason for oxidative stress in patients with renal failure is the underlying disease itself. Renal toxicity, ischemia/reperfusion and immunological disorders of the kidney result in an elevated formation of reactive oxygen species active in the pathogenesis of kidney disease. However, treatment procedures were also shown to induce oxidative stress. Increased formation of free radicals leads to an accelerated lipid peroxidation (LPO). Furthermore, secondary aldehydic LPO products, e.g. malondialdehyde (MDA) and 4-hydroxynonenal (HNE), are formed which were shown to deplete antioxidants, inhibit protein syntheses, mitochondrial respiration, and enzyme functions. F2-isoprostanes, also metabolites of polyunsaturated fatty acids, represent an additional in vivo marker of oxidative stress. Both isoprostanes and aldehydic LPO products can be removed by hemodialysis, however, this suggests only in part their binding to other molecules which cause tissue damage. Protein carbonyls are end-products of such interventions. Oxysterols, another form of free-radical initiated oxidation products, were shown to initiate atherosclerosis and plaque formation increasing dramatically the risk of coronary heart disease. Today there is no doubt that the correction of the oxidant/antioxidant imbalance in patients with chronic renal failure is an important approach for the reduction of the risk of those patients to develop cardiovascular disorders. The complete correction of renal anemia represents an effective means of strengthening antioxidant capacity and, therefore, of reducting cardiovascular risk potential.
Cardiovascular Diseases↗
Distinct Ca2+ thresholds determine cytochrome c release or permeability transition pore opening in brain mitochondria.
In diseases associated with neuronal degeneration, such as Alzheimer's or cerebral ischemia, the cytosolic Ca2+ concentration ([Ca2+]cyt) is pathologically elevated. It is still unclear, however, under which conditions Ca2+ induces either apoptotic or necrotic neuronal cell death. Studying respiration and morphology of rat brain mitochondria, we found that extramitochondrial [Ca2+] above 1 M causes reversible release of cytochrome c, a key trigger of apoptosis. This event was NO-independent but required Ca2+ influx into the mitochondrial matrix. The mitochondrial permeability transition pore (PTP), widely thought to underlie cytochrome c release, was not involved. In contrast to noncerebral tissue, only relatively high [Ca2+] (is approximately equal to 200 M) opened PTP and ruptured mitochondria. Our findings might reflect a fundamental mechanism to protect postmitotic neuronal tissue against necrotic devastation and inflammation.
Animals↗
Adaptation of protein carbonyl detection to the requirements of proteome analysis demonstrated for hypoxia/reoxygenation in isolated rat liver mitochondria.
The key technique in proteome analysis is high-resolution two-dimensional (2D) electrophoretic separation of proteins from biological samples. This method combines isoelectric focusing (IEF) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Derivatization of protein carbonyls with 2, 4-dinitrophenylhydrazine (DNPH) and subsequent anti-dinitrophenyl (DNP) immunoblotting is widely used for the detection of oxidatively modified proteins. In previous studies on adapting this method to 2D electrophoresis the derivatization step was carried out before and after the 2D procedure, resulting in an altered spot pattern and high background staining, respectively. The aim of the present experiments was to develop a method for protein derivatization with DNPH between the IEF and the SDS-PAGE steps. Mitochondria were exposed to 10 min hypoxia and 5 min reoxygenation. After IEF using immobilized pH gradients the gel strips were incubated in DNPH/trifluoroacetic acid/SDS for 20 min and neutralized, and SDS-PAGE was performed. Proteins were either stained with Coomassie dye or subjected to Western blotting using anti-DNP IgG. Gels and blots were scanned and matched to a master gel, and the relative carbonyl content of each spot was calculated and compared for five experiments. Importantly, the spot patterns in DNPH-treated and untreated gels were not different. Protein carbonyls could be detected in 59 of the 125 matched spots. Although there was no significant increase in the total protein carbonyl content after hypoxia/reoxygenation, eighteen 2D spots exhibited an increase in carbonyl content. However, most protein spots did not show a change or even a decline (4 spots) in protein carbonyls.
Animals↗
Oxidative stress in lung tissue induced by CO(2) pneumoperitoneum in the rat.
BACKGROUND: Clinical trials have found that the pneumoperitoneum has potentially hazardous side effects. The biochemical basis of organ injury induced by pneumoperitoneum is, however, not well defined. Since oxidative stress is believed to play an important role in many pathological conditions, we set out to examine oxidative stress markers in the lung, liver, kidney, and pancreas by using a rat model of laparoscopy with CO(2) pneumoperitoneum and comparing it to a group with gasless laparoscopy. METHODS: Malondialdehyde (for lipid peroxidation), protein-bound carbonyls (for protein oxidation), reduced and oxidized glutathione, and the neutrophil marker myeloperoxidase were evaluated in tissue homogenates at 2 h, 6 h, and 18 h after laparoscopy. Immunoblotting was used to analyze the modification of lung proteins by 4-hydroxynonenal at 6 h. RESULTS: Significant lipid peroxidation was found selectively in lungs at 2 h and 6 h after CO(2) pneumoperitoneum. This was accompanied by a loss of glutathione but only minor protein oxidation. Further, lung proteins were clearly modified by the aldehydic product of lipid peroxidation 4-hydroxynonenal. Myeloperoxidase in lungs increased continuously up to 18 h in both experimental groups, but there were higher levels in the group with pneumoperitoneum. CONCLUSION: Oxidative stress is likely to contribute to the impairment of pulmonary function after laparoscopic operations using a CO(2) pneumoperitoneum.
Analysis of Variance↗
A sensitive gas chromatography-mass spectrometry assay reveals increased levels of monohydroxyeicosatetraenoic acid isomers in human plasma after extracorporeal photoimmunotherapy and under in vitro ultraviolet A exposure.
Extracorporeal photoimmunotherapy (photopheresis) is a highly effective therapy in the treatment of various disorders. Although extracorporeal photoimmunotherapy has been successfully used for more than 10 y, its mechanism of action is still unclear. The formation of reactive oxygen species have been implicated in extracorporeal photoimmunotherapy, but malonyl dialdehyde as a marker of systemic lipid peroxidation did not increase significantly during treatment. To investigate further the involvement of reactive oxygen species in extracorporeal photoimmunotherapy, we have introduced a highly sensitive negative ion gas chromatography-mass spectrometry based method for quantitating oxygenated arachidonic acid isomers (hydroxyeicosatetraenoic acids) in plasma samples of patients treated with extracorporeal photoimmunotherapy. In the plasma of healthy volunteers pmole amounts of 2-, 3-, 5-, 8-12-, and 15-hydroxyeicosatetraenoic acid were detected and we observed a dose-dependent augmentation in these metabolites when the blood was irradiated with increasing doses of ultraviolet A in the presence of the photosensitizer 8-methoxypsoralen. Analysis of plasma samples obtained from patients before and after extracorporeal photoimmunotherapy revealed a characteristic increase in total hydroxyeicosatetraenoic acid levels, particularly of 5-hydroxyeicosatetraenoic acid which contributed 80% to the sum of all hydroxyeicosatetraenoic acid isomers. Chiral phase high-performance liquid chromatography indicated almost equal amounts of 5S- and 5R-hydroxyeicosatetraenoic acid suggesting that the majority of lipid peroxidation products are formed via nonenzymatic oxidation reactions.
Gas Chromatography-Mass Spectrometry↗
Induction of permeability transition in pancreatic mitochondria by cerulein in rats.
Hyperstimulation with cholecystokinin analogue cerulein induces a mild edematous pancreatitis in rats. There is evidence for a diminished energy metabolism of acinar cells in this experimental model. The aim of this study was to demonstrate permeability transition of the mitochondrial inner membrane as an early change in mitochondrial function and morphology. As functional parameters, the respiration and membrane potential of mitochondria isolated from control and cerulein-treated animals were measured, and changes in volume and morphology were investigated by swelling experiments and electron microscopy. Five hours after the first injection of cerulein, the leak respiration was nearly doubled and the resting membrane potential was decreased by about 17 mV. These alterations were reversed by extramitochondrial ADP or did not occur when cyclosporin A was added to the mitochondrial incubation. A considerable portion of the mitochondria isolated from cerulein-treated animals was swollen and showed dramatic changes in morphology such as a wrinkled outer membrane and the loss of a distinct cristae structure. These data provide evidence for the opening of the mitochondrial permeability transition pore at an early stage of cerulein induced pancreatitis. This suggests that the permeability transition is an initiating event for lysis of individual mitochondria and the initiation of apoptosis and/or necrosis, as had been shown to occur in this experimental model.
Animals↗
Evaluation of UVA-mediated oxidative damage to proteins and lipids in extracorporeal photoimmunotherapy.
The combination of UVA and 8-methoxypsoralen (8-MOP) is known for the ability to produce reactive oxygen species (ROS) that react subsequently with DNA, lipids and proteins. In most studies concerned with UVA effects mediated by free radicals, UVA doses higher than those exhibiting beneficial clinical results in extracorporeal photoimmunotherapy (ECPI) were used. The present study was undertaken to determine markers of oxidative stress in plasma and cells from the buffy coat using conditions relevant for ECPI (cumulative UVA dose at the sample level < or = 2 J/cm2). Plasma exposed to UVA of 20 J/cm2 resulted in protein oxidation as well in crosslinking and fragmentation revealed by electrophoresis. Exposure of the buffy coat and plasma to considerably lower doses of UVA (up to 2 J/cm2) combined with various 8-MOP concentrations resulted neither in an increase of malondialdehyde as a marker of lipid peroxidation nor in a changed electrophoretic protein pattern. In these same experiments the total antioxidative capacity decreased to 65% of the initial value, suggesting that the antioxidative defense of plasma is able to cope with oxidative stress under ECPI conditions. These results were confirmed by data from 10 patients with scleroderma or cutaneous T-cell lymphoma during ECPI treatment. The present results suggest that, although ROS are formed during ECPI, gross oxidative damage does not occur. It is, however, possible, that specific effects mediated by oxygen radicals may co-trigger the photoimmunomodulatory effects of ECPI.
Blood Proteins↗
Occurrence of oxidatively modified proteins: an early event in experimental acute pancreatitis.
Free radical-mediated injury is believed to play a key role in the pathogenesis of acute pancreatitis (AP). Therefore, oxidative damage of proteins may be an important event in the development of AP. The present study was performed to investigate oxidative protein modification, quantified as 2,4-dinitrophenylhydrazine-reactive protein-carbonyls, during the time course of taurocholate-induced pancreatitis of the rat and to analyze oxidatively modified proteins by Western blotting. Protein modification in pancreatic homogenates was found as early as 30 min after induction of severe AP with 3% taurocholate preceding the elevation of serum amylase activity and the increase of malondialdehyde in the tissue. A correlation of protein-carbonyl contents to a score of pancreatic macroscopic alterations (r = .69) and to the wet weight/dry weight ratio (r = .65) was found. Infusion of 5% taurocholate resulted in fulminant AP with high lethality during the 24 h of the experiment. However, rats surviving showed significantly lower level of protein-carbonyls than animals that died between 20-24 h after AP induction. The quantitative data were confirmed by the intensity of immunostained protein-carbonyls. The present data show a rather uniform increase in the staining pattern not revealing single, selectively damaged proteins. The aldehydic product of lipid peroxidation 4-hydroxynonenal (HNE) is known for its reactivity towards proteins. Interestingly, an antibody raised against protein-bound HNE did not indicate an increased protein modification by this aldehyde. In conclusion, experimental AP is characterized by an early oxidative protein modification, possibly contributing to functional impairment of the pancreas. This protein alteration may not be mediated by HNE.
Acute Disease↗
Compositional and functional changes of low-density lipoprotein during hemodialysis in patients with ESRD.
BACKGROUND: This study focused on the effects of hemodialysis on the atherogenic properties of low density lipoprotein (LDL) in patients with end-stage renal disease (ESRD). The impact of cholesterol ester transfer protein (CETP) activity and lipolysis on LDL composition, particularly the changes during hemodialysis, was investigated. METHODS: Blood was drawn from 15 normotriglyceridemic (NTG) and 15 hypertriglyceridemic patients [HTG; triglycerides (TG) < 2.2 mmol/liter] before hemodialysis, during (1.5 hr after the beginning of anticoagulation) and at the end of treatment. In each sample, lipid values and CETP activity were measured. LDL was prepared and characterized by its components and diameters (2 to 16% PAGGE). To investigate the functional properties of LDL, fractions obtained from NTG and HTG patients were incubated with human skin fibroblasts and a cell line of murine macrophages (P388), and cholesterol ester formation rates were measured. RESULTS: In comparison to LDL from NTG patients at baseline, HTG-LDL were enriched in triglycerides (P < 0.02), depleted in cholesterol proportion (P < 0.01) and small in size (P < 0.001). These LDL induced the cholesterol esterification rates (50 micrograms/mL LDL-protein) in a twofold greater unsaturation in macrophages when compared to LDL from NTG patients (P < 0.04). The rates in fibroblasts were reduced by approximately half (P < 0.05). During hemodialysis, LDL were decreased in size (P < 0.001) and depleted in TG (P < 0.01), particularly in the hypertriglyceridemic state. Although CETP activity increased during hemodialysis (P < 0.001), the cholesterol content remained unchanged. When HTG-LDL obtained during hemodialysis were incubated with cells, esterification rates particularly in macrophages were markedly accelerated in comparison to the unmodified lipoprotein at baseline (P < 0.05). CONCLUSION: LDL from HTG patients with ESRD was TG-enriched, CH-depleted and smaller in size. As the intracellular esterification rates induced by LDL were related to the cellular uptake, these LDL were a superior substrate for murine macrophages with the tendency of intracellular accumulation, and an inferior substrate for fibroblasts suggesting a decreased uptake by the specific receptor pathway. TG-depletion of LDL during hemodialysis, particularly in HTG patients due to a lipase-mediated TG-hydrolysis, increased these effects in macrophages. We suggest that the alterations of LDL that occur during repeated hemodialysis in vivo could contribute to the high prevalence of premature atherosclerosis found in HTG patients with ESRD.
Adult↗
Comparison of protein oxidation and aldehyde formation during oxidative stress in isolated mitochondria.
Oxidative stress is known to cause oxidative protein modification and the generation of reactive aldehydes derived from lipid peroxidation. Extent and kinetics of both processes were investigated during oxidative damage of isolated rat liver mitochondria treated with iron/ascorbate. The monofunctional aldehydes 4-hydroxynonenal (4-HNE), n-hexanal, n-pentanal, n-nonanal, n-heptanal, 2-octenal, 4-hydroxydecenal as well as thiobarbituric acid reactive substances (TBARS) were detected. The kinetics of aldehyde generation showed a lag-phase preceding an exponential increase. In contrast, oxidative protein modification, assessed as 2,4-dinitrophenylhydrazine (DNPH) reactive protein-bound carbonyls, continuously increased without detectable lag-phase. Western blot analysis confirmed these findings but did not allow the identification of individual proteins preferentially oxidized. Protein modification by 4-HNE, determined by immunoblotting, was in parallel to the formation of this aldehyde determined by HPLC. These results suggest that protein oxidation occurs during the time of functional decline of mitochondria, i.e. in the lag-phase of lipid peroxidation. This protein modification seems not to be caused by 4-HNE.
Aldehydes↗
LDL size distribution in relation to insulin sensitivity and lipoprotein pattern in young and healthy subjects.
OBJECTIVE: Smaller LDL particles are associated with an increased risk for coronary artery disease and have been found predominantly in subjects with the insulin resistance syndrome. Although insulin resistance has been suggested to be a basic defect, little is known about the relation between this predisposing factor (and associated metabolic disturbances) and LDL size distribution in young and metabolically healthy subjects. In the present study, we investigated the relation between insulin sensitivity, lipoprotein distribution, and LDL patterns in young adults to increase the understanding of the development of metabolic risk factors in an early phase of the life span. RESEARCH DESIGN AND METHODS: Young, clinically healthy subjects (n = 50; age 21.1-30.6 years) were enrolled in the study. Glucose metabolism was characterized by peripheral insulin sensitivity assessed by a hyperinsulinemic-euglycemic clamp and by levels of fasting insulin, C-peptide, and glucose. Lipoproteins were measured, and LDL fractions were additionally characterized by the diameter of the major LDL peak, estimated by 2-16% polyacrylamide gradient gel electrophoresis. Cholesterol ester transfer was estimated with a fluorescent spectroscopic method that measures the transfer of fluorescent cholesteryl linoleate between exogenous donor and acceptor particles. In this assay system, cholesterylester transfer protein (CETP) activity was only influenced by the plasma CETP concentration therefore reflecting more likely the CETP mass. RESULTS: In the entire study group, 47 subjects had LDL phenotype A (LDL diameter > 25.75 nm) and 3 subjects had an intermediate phenotype (25.50-25.75 nm). An interrelation between LDL size and LDL triglyceride (LDL-TG) per apolipoprotein (apo) B (Spearman's rank correlation analysis; r = -0.78; P < 0.001) or LDL cholesterol ester (CE) per apoB (r = 0.58, P < 0.001) was found, and 39% of the plasma samples studied were characterized by a monodispersed LDL pattern. Furthermore, LDL diameters correlated negatively with total TGs (men: r = -0.52, P < 0.001; women: r = -0.61, P < 0.001) and positively with insulin sensitivity (total population: r = 0.54, P < 0.001). In addition, LDL size was inversely related to the [VLDL + LDL cholesterol (CH)]/HDL-CH ratio and positively to the HDL-CE/TG ratio, which were both related vice versa to CETP activity levels. A direct relation between CETP activity levels and LDL size or composition was not observed. In a linear regression analysis including parameters of lipoprotein metabolism (TG, HDL cholesterol, CETP activity level), glucose metabolism (insulin sensitivity, fasting insulin), and sex, only TGs predicted significantly for 62% of LDL size variability. If the total study population was evaluated according to quintiles of insulin sensitivity, increasing TGs (analysis of variance, Scheffé test; P < 0.05) and CETP activity levels (P < 0.05) were combined with decreasing LDL particle diameters (P < 0.05) and with a preponderance of a monodispersed LDL pattern (60%) in the most insulin-resistant group. CONCLUSIONS: Among parameters of the lipoprotein and glucose metabolism, total TG is the single most important factor affecting LDL size variability, even in young adults. If the study population is evaluated according to insulin sensitivity, lipoprotein pattern is altered in a more atherogenic manner in the most insulin-resistant subjects. In this group, increasing TG and CETP activity levels are associated with decreasing LDL particle diameters and preponderance of a monodispersed LDL pattern. Although increasing CETP levels are combined with this particular lipoprotein profile, a direct relation to LDL size and composition is not found.
Adult↗
Short-term impairment of energy production in isolated rat liver mitochondria by hypoxia/reoxygenation: involvement of oxidative protein modification.
The aim of the present study was to elucidate the role of mitochondria in liver impairment after ischaemia/reperfusion. It is commonly assumed that mitochondria are in part responsible for tissue damage by impaired oxidative phosphorylation as a consequence of the attack of radicals generated within the mitochondria. The principal support for this hypothesis was found by exposing isolated mitochondria to temporary hypoxia in combination with alterations of substrate supply. Rat liver mitochondria treated in this way responded with impaired ADP-stimulated respiration after reoxygenation, which decreased with time of hypoxia and reoxygenation. The decline of the activity of the NADH-cytochrome c-oxidoreductase complex found under these conditions is likely to cause the drop in active respiration. No changes in the content of respiratory chain complexes, determined by Blue Native PAGE, could be demonstrated. However, oxidative modifications of mitochondrial proteins, indicated by carbonyl formation, were found. Likewise, products of lipid peroxidation, such as lipid peroxides and malondialdehyde, were formed. Mitochondria were still able to build up a transmembrane potential and did not show drastic changes in membrane conductivity after hypoxia/reoxygenation stress. The presence of water-soluble antioxidants exhibited a beneficial effect, diminishing the decline of active respiration after 5 min of hypoxia and 10 min of reoxygenation. These observations strongly suggest that mitochondria play a pathogenic role in ischaemia/reperfusion injury, which is at least in part mediated by an oxygen-derived free-radical-linked mechanism.
Animals↗
2,7-Dihydrodichlorofluorescein diacetate as a fluorescent marker for peroxynitrite formation.
Reactive oxygen species (ROS) have been implicated as an important causative factor in cell damage, including apoptosis and necrosis. Their proposed actions comprise lipid peroxidation, DNA damage, destruction of the mitochondrial respiratory chain and protein modifications. Recent experiments underline the importance of peroxynitrite, the reaction product of the two potent reactive species nitric oxide and superoxide. Several fluorogenic compounds have been used in order to determine ROS formation in living cells. Besides dihydrorhodamine-123 (DHR-123), at present mostly applied to monitor peroxynitrite, 2,7-dihydrodichlorofluorescein (DCF-H) is used for detection of hydrogen peroxide and nitric oxide. We employed a cell free approach to evaluate the specificity and sensitivity of DCF-H to various oxidizing compounds. Our studies imply that DCF-H is much more sensitive to peroxynitrite oxidation than any other compound tested. In order to study peroxynitrite generation within individual cells, primary glial cultures loaded with DCF-H were monitored with a laser scanning microscope. Microglia, stimulated to simultaneously produce the peroxynitrite precursors nitric oxide and superoxide, displayed the greatest increase in DCF fluorescence, whereas microglia producing either nitric oxide or superoxide alone showed a relatively small increase in DCF fluorescence. In conclusion, DCF-H was demonstrated to be an excellent peroxynitrite marker with the potential to detect peroxynitrite formation in living cells.
Animals↗
Chloroquine effects on intrauterine and postnatal dendritic maturation of hippocampal neurons and on lipid composition of the developing rat brain.
The aim of the study was to analyse the intrauterine effects of Chloroquine on the dendritic maturation in the hippocampal region under considering of the lipid composition in brain tissue. 131 brains of rat pups from day 22 of pregnancy and 49 brains from offsprings from day 7 of life were investigated. The findings indicate changes in the geometric dendritic architecture of the CA3 neurons on the 7th day of life. The length of apical shaft, apical dendrites and basilar dendrites of the CA3 neurons showed a significant elongation (p < 0.05) under low doses of Chloroquine. Furthermore a early considerable formation of dendritic spines during the intrauterine period could be observed for CA1 spines at the day 22 p.c. A significant increase of the fatty acids, a reduced amount of sphingomyelines, cephalines and gangliosides was found. These results underline the fact of a mild toxic effect under a low dosis of Chloroquine in our model.
Administration, Oral↗
Micromolar calcium prevents isolated rat liver mitochondria from anoxia-reoxygenation injury.
Rat liver mitochondria were exposed to extramitochondrial free calcium between 0 and 5 microM and/or 5 minutes of anoxia followed by 10 minutes of reoxygenation. At concentrations higher than 4 microM, the membrane potential collapsed indicating the permeability transition of the mitochondrial membrane. Anoxia-reoxygenation shifted this transition to lower calcium concentrations. Anoxia-reoxygenation alone resulted in the decrease of ADP stimulated respiration down to about 40% of its initial value. Between 1 and 2 microM, a protective effect in terms of respiration and oxidative protein modification was found. It is concluded that calcium may suppress the formation of reactive oxygen species during anoxia-reoxygenation before permeability transition occurs.
Animals↗
Role of endogenous and exogenous antioxidants in the defence against functional damage and lipid peroxidation in rat liver mitochondria.
Mitochondria are cellular organelles where the generation of reactive oxygen species may be high. They are, however, effectively protected by their high capacities of antioxidative systems, as enzymes and either water or lipid soluble low molecular weight antioxidants. These antioxidative defence systems can be effectively regenerated after or during an oxidative stress as long as the mitochondria are in an energized state. Energization of mitochondria mainly depends on the availability of suitable respiratory substrates which can provide hydrogen for the reduction of either the glutathione- or alpha-tocopherol-system, since GSH is regenerated by glutathione reductase with the substrate NADPH and the alpha-tocopheroxyl-radical likely by reduced coenzyme Q. It was shown that mitochondria do not undergo damages as long as they can keep a high energy state. The delicate balance between prooxidative/antioxidative activities can be shifted towards oxidation, if experimentally prooxidants were added. After exhaustion of the antioxidative defence systems damages of mitochondrial functions become expressed followed by membrane injuries along with the oxidation and degradation of mitochondrial lipids and proteins leading finally to the total degradation of the mitochondria. Extramitochondrial antioxidants may assist the mitochondrial antioxidative defence systems in a complex way, whereby particularly ascorbic acid can act both as prooxidant and as antioxidant.
Animals↗