The labile iron pool in monocytes reflects the activity of the atherosclerotic process in men with chronic cardiovascular disease.

The study investigates the relationship between the labile iron pool (LIP) in circulating monocytes and markers of iron metabolism, inflammation, oxidative stress, endothelial dysfunction and arterial elasticity in patients with chronic cardiovascular disease and in healthy volunteers. The patients with a history of CVEs had significantly higher LIP values than did the control group (1.94+/-0.46 microM vs. 1.62+/-0.49 microM, p=0.02). Except for the leukocyte number (WBCs), the groups did not differ in other inflammatory markers (CRPus, CD 163, MPO, MMP-1). Similarly, there were no differences in the markers of endothelial dysfunction (ICAM, VCAM, E-selectin, vWF). The CVE group had higher pulse pressures, levels of markers of impaired arterial elasticity (AI, Young´s modulus, pulsatility, stiffness index), IMT values and ABI values. The LIP concentration was significantly correlated with the transferrin receptor/ferritin ratio, hepcidin levels, VFT content and the ABI and ET values. Patients with a history of CVE have significantly higher concentrations of iron in their intracellular LIP in circulating monocytes than do healthy controls. The independent and significant correlation of LIP with markers of the progression of atherosclerosis and arterial stiffness suggests LIP as a possible novel marker of atherosclerotic activity.

Glucose and its metabolites have distinct effects on the calcium-induced mitochondrial permeability transition.

Mitochondrial production of reactive oxygen species (ROS) due to up-regulated glucose oxidation is thought to play a crucial, unifying role in the pathogenesis of chronic complications associated with diabetes mellitus. Mitochondrial permeability transition (MPT) is an interesting phenomenon involved in calcium signalling and cell death. We investigated the effects of glucose and several of its metabolites on calcium-induced MPT (measured as mitochondrial swelling) in isolated rat liver mitochondria. The presence of glucose, glucose 1-phosphate (both at 30 mM) or methylglyoxal (6 mM) significantly slowed calcium-induced mitochondrial swelling. Thirty mM glucose also resulted in a significant delay of MPT onset. In contrast, 30 mM fructose 6-phosphate accelerated swelling, whereas glucose 6-phosphate did not influence the MPT. The calcium binding potentials of the three hexose phosphates were tested and found similar. In vitro hydrogen peroxide production by mitochondria respiring on succinate in the presence of rotenone was independent of mitochondrial membrane potential and increased transiently during calcium-induced MPT. Inhibition of MPT with cyclosporine A resulted in decreased mitochondrial ROS production in response to calcium. In contrast, inhibition of MPT by methylglyoxal was accompanied by increased ROS production in response to calcium. In conclusion, we confirm that methylglyoxal is a potent inhibitor of MPT. In addition, high levels of glucose, glucose 1-phosphate and fructose 6-phosphate can also affect MPT. Methylglyoxal simultaneously inhibits MPT and increases mitochondrial ROS production in response to calcium. Our findings provide a novel context for the role of MPT in glucose sensing and the cellular toxicity caused by methylglyoxal.

Changes of corneal optical properties after UVB irradiation investigated spectrophotometrically.

Ozone depletion leads to an increase in UV rays of solar radiation reaching the surface of the Earth which is harmful to biological systems. Of the eye, the cornea is directly open to increased amount of UV rays of which mainly UVB rays are capable to induce reactive oxygen species damaging the cells. Previous studies showed that the irradiation of the cornea with UVB rays leads to morphological as well as metabolic disturbances of the cornea. Also, corneal hydration and corneal light absorption are increased after UVB rays. These changes were observed after five days of repeated irradiation of the cornea with UVB rays. The aim of the present paper was to examine how early the changes of corneal hydration and light absorption occur after UVB irradiation. The rabbit corneas were irradiated with UVB rays for one, two, three or four days. Corneal light absorption was examined spectrophotometrically and corneal hydration measured by pachymeter (as corneal thickness). Results show that changes of corneal hydration and light absorption appear early after UVB irradiation and increase along with the number of irradiations. In conclusion, irradiation of the rabbit cornea with UVB rays leads to harmful changes of its optical properties.

Culture methods of glomerular podocytes.

Podocytes (glomerular visceral epithelial cells) cover the exterior surface of the glomerular capillaries and contribute to the glomerular filtration membrane. Failure of podocyte function is involved in the progression of chronic glomerular disease; accordingly, research interest into podocyte biology is driven by the need for better protection and perhaps recovery of these cells in renal diseases. This review aims at summarizing available techniques for podocyte cell cultures from both the past and present, with special attention to the currently used methods. The establishment of classical primary cultures is based on isolation of glomeruli by differential sieving. Plating of glomeruli onto a collagen surface is followed by an outgrowth of cobblestone-like cells that, after replating, differentiate into arborized, mature podocytes. Currently, the majority of research studies use immortalized podocytic cell lines most often derived from transgenic mice bearing a conditional immortalizing gene. The podocytes can also be collected and cultured from healthy or diseased animal or patient urine. The urinary podocytes obtained from subjects with active glomerulopathies display higher proliferation potential and viability in vitro, perhaps due to disease-induced transdifferentiation. Finally, a list of phenotypic markers useful for identification and characterization of the cultured podocytic elements is provided.

Differences in activities of antioxidant superoxide dismutase, glutathione peroxidase and prooxidant xanthine oxidoreductase/xanthine oxidase in the normal corneal epithelium of various mammals.

Under normal conditions, antioxidants at the corneal surface are balanced with the production of reactive oxygen species without any toxic effects. Danger from oxidative stress appears when natural antioxidants are overwhelmed leading to antioxidant/prooxidant imbalance. The aim of the present study was to examine the activities of enzymes contributing to the antioxidant/prooxidant balance in normal corneal epithelium of various mammals. The enzyme activities of antioxidant superoxide dismutase and glutathione peroxidase, as well as prooxidant xanthine oxidoreductase/xanthine oxidase were examined using biochemical methods. Results show that superoxide dismutase activity is high in rabbits and guinea pigs, whereas in pigs the activity is low and in cows it is nearly absent. In contrast, glutathione peroxidase activity is high in cows, pigs and rabbits, whereas in guinea pigs the activity is low. As far as prooxidant enzymes are concerned, elevated xanthine oxidoreductase/xanthine oxidase activities were found in rabbits, lower activities in guinea pigs, very low activity in cows and no activity in pigs. In conclusion, the above results demonstrate inter-species variations in activities of enzymes participating in antioxidant/prooxidant balance in the corneal epithelium. It is suggested that the levels of antioxidant and prooxidant enzymes studied in the corneal epithelium might be associated with the diurnal or nocturnal activity of animals. UV rays decompose hydrogen peroxide to damaging hydroxyl radicals and perhaps for this reason large animals with diurnal activity (cow, pig) require more effective peroxide removal (high glutathione peroxidase activity) together with the suppression of peroxide production (low superoxide dismutase activity, low xanthine oxidoreductase activity).

UV Rays, the prooxidant/antioxidant imbalance in the cornea and oxidative eye damage.

In this minireview, the factors involved in the development of corneal injury due to an increased amount of UVB rays are summarized. Experimental studies have shown that an increased number of UVB rays leads to a profound decrease in corneal antioxidants (high molecular weight, antioxidant enzymes as well as low molecular weight, mainly ascorbic acid) so that a prooxidant/antioxidant imbalance appears. The decrease of corneal antioxidant protective mechanisms results in oxidative injury of the cornea and causes damage of the inner parts of the eye by UVB rays and by reactive oxygen species generated by them.

Quinolinic acid-iron(ii) complexes: slow autoxidation, but enhanced hydroxyl radical production in the Fenton reaction.

Quinolinate (pyridine-2,3-dicarboxylic acid, Quin) is a neurotoxic tryptophan metabolite produced mainly by immune-activated macrophages. It is implicated in the pathogenesis of several brain disorders including HIV-associated dementia. Previous evidence suggests that Quin may exert its neurotoxic effects not only as an agonist on the NMDA subtype of glutamate receptor, but also by a receptor-independent mechanism. In this study we address ability of ferrous quinolinate chelates to generate reactive oxygen species. Autoxidation of Quin-Fe(II) complexes, followed in Hepes buffer at pH 7.4 using ferrozine as the Fe(II) detector, was found to be markedly slower in comparison with iron unchelated or complexed to citrate or ADP. The rate of Quin-Fe(II) autoxidation depends on pH (squared hydroxide anion concentration), is catalyzed by inorganic phosphate, and in both Hepes and phosphate buffers inversely depends on Quin concentration. These observations can be explained in terms of anion catalysis of hexaaquairon(II) autoxidation, acting mainly on the unchelated or partially chelated pool of iron. In order to follow hydroxyl radical generation in the Fenton chemistry, electron paramagnetic resonance (EPR) spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) was employed. In the mixture consisting of 100 mM DMPO, 0.1 mM Fe(II), and 8.8 mM hydrogen peroxide in phosphate buffer pH 7.4, 0.5 mM Quin approximately doubled the yield of DMPO-OH adduct, and higher Quin concentration increased the spin adduct signal even more. When DMPO-OH was pre-formed using Ti3+ /hydrogen peroxide followed by peroxide removal with catalase, only addition of Quin-Fe(II), but not Fe(II), Fe(III), or Quin-Fe(III), significantly promoted decomposition of pre-formed DMPO-OH. Furthermore, reaction of Quin-Fe(II) with hydrogen peroxide leads to initial iron oxidation followed by appearance of iron redox cycling, detected as slow accumulation of ferrous ferrozine complex. This phenomenon cannot be abolished by subsequent addition of catalase. Thus, we propose that redox cycling of iron by a Quin derivative, formed by initial attack of hydroxyl radicals on Quin, rather than effects of iron complexes on DMPO-OH stability or redox cycling by hydrogen peroxide, is responsible for enhanced DMPO-OH signal in the presence of Quin. The present observations suggest that Quin-Fe(II) complexes display significant pro-oxidant characteristics that could have implications for Quin neurotoxicity.

Molecular mechanisms associated with long-term consolidation of the NMDA signals.

The N-methyl-D-aspartate (NMDA) subtype of glutamate receptors in the mammalian brain plays a central role in synaptic plasticity underlying refinement of neuronal connections during development, or processes like long-term potentiation (LTP), learning and memory. On the other hand, over-activation of glutamate receptors leading to neurodegeneration has been implicated in major areas of brain pathology. Any sustained effect of a transient NMDA receptor activation is likely to involve signaling to the nucleus and coordinated changes in gene expression. Classically, a set of immediate-early genes is induced first; some of them are themselves transcription factors that control expression of other target genes. This review deals with the induction of Fos, Jun and Egr (Krox) transcription factors in response to NMDA or non-NMDA (AMPA/kainate) ionotropic receptor agonists in vivo or in neuronal cultures in vitro. In addition, the mechanism of induction of a model immediate-early gene c-fos in response to Ca2+ influx through activated NMDA receptors or voltage-sensitive calcium channels is discussed. Both modes of calcium entry induce c-fos via activation of multiple signaling pathways that converge on constitutive transcription factors cAMP-response element-binding protein (CREB), serum response factor (SRF) and a ternary complex factor (TCF), such as Elk-1. In contrast to the traditional view of the NMDA receptor as a ligand-gated calcium channel, whose activation leads to calcium influx and activation of Ca2+/calmodulin-dependent kinases, recent evidence highlights involvement of the Ras/ mitogen-activated protein kinase (MAPK) pathway in the NMDA signaling to the nucleus.

ICRF-187 (dexrazoxan) protects from adriamycin-induced nephrotic syndrome in rats.

BACKGROUND: Reactive oxygen species produced during metabolism of adriamycin are purported to play an important role in the pathogenesis of experimental adriamycin nephropathy in rats. ICRF-187 (dexrazoxan, Cardioxan), an iron chelator, has been shown to inhibit adriamycin-induced formation of hydroxyl radical and to decrease adriamycin cardiotoxicity in oncological patients. The aim of our study was to assess the putative protective role of ICRF-187 in adriamycin nephropathy by evaluating the possible participation of free radicals in its pathogenesis. METHODS: We examined five experimental groups. Group A, received a single dose of adriamycin (5 mg/kg bw i.v.), group CA was given a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration, group CCA received a single dose of ICRF-187 (100 mg/kg bw i.v.) before adriamycin administration followed by three weekly intraperitoneal injections (100 mg/kg bw) ICRF-187. Group CC received one dose of ICRF-187 (100 mg/kg bw i.v.) followed by three weekly intraperitoneal injections of ICRF-187, and group N served as control receiving saline. Common biochemical parameters, malondialdehyde (MDA) and antioxidant enzymes (glutathione peroxidase--GPx and superoxide dismutase--SOD) in blood and kidney homogenates were measure and histology of the kidney was studied after the rats were sacrificed. RESULTS: Full-blown nephrotic syndrome developed after 3 weeks only in A rats. Nephrotic syndrome was completely prevented in all ICRF-187 treated rats (CA, CCA). Proteinuria was significantly increased in A rats (108.2 + 48.4 mg/l of glomerular filtrate) compared with CA (12.4 + 6.8 mg/l, P < 0.0001) and with N (6.1 + 3.5 mg/l, P < 0.0001). Total MDA in erythrocytes was significantly increased only in A rats (1.7 + 0.3 micromol/l) and was completely normalized by ICRF-187 in CA (1.1 + 0.2 micromol/l, P < 0.001). Total TBARS and MDA in kidney homogenates were significantly elevated in groups with repeated administration of ICRF-187 (CC and CCA rats) compared to N, CA, A groups. Activity of GPx and SOD in kidney homogenate and in erythrocytes was not significantly increased by ICRF-187 in adriamycin treated rats. Histologic changes in A rats resembled minimal change nephropathy with fusion of foot processes and hyaline casts in tubules. There was only minimal mesangial proliferation and perivascular mast cell infiltrates in all groups of ICRF-187-treated rats. CONCLUSIONS: We conclude that ICRF-187, probably by chelation iron, completely protected rats from adriamycin-induced nephrotic syndrome. It supports the role of iron-mediated reactive oxygen species in the development of this type of glomerular injury. However, repeated administration of ICRF-187 alone is able to increase parameters of oxidative stress in the kidney.

The effect of quinolinate on rat brain lipid peroxidation is dependent on iron.

Quinolinate, an endogenous excitotoxic metabolite of tryptophan with affinity to the N-methyl-D-aspartate type of glutamate receptor, is known as a stimulator of lipid peroxidation in vitro [Neurochem. Res. (1991) 16, 1139-1143]. To analyse the mechanism of this quinolinate toxicity we used the thiobarbituric acid test to measure malondialdehyde in homogenates of rat cerebral hemispheres incubated in air at 37 degrees C for 30 min in the presence of 0.015-15.0 mM quinolinate, endogenous iron or 0.5-2.0 microM FeSO4 and with or without 250 microM ascorbate. Quinolinate in the concentrations of 0.15-2.5 mM stimulated lipid peroxidation in the homogenates in the presence of 0.5-2.0 microM Fe2+. However, quinolinate concentrations higher than 3.0 mM inhibited the lipid peroxidation at all the tested concentrations of iron. In the presence of a potent iron chelator (10 microM deferoxamine) quinolinate completely failed to induce lipid peroxidation in rat brain homogenates. Spectral analysis revealed that quinolinate is able to form a complex with Fe2+. The results suggest that quinolinate does not have a direct peroxidative effect, but that it modulates lipid peroxidation via its interaction with iron.

The influence of cyclosporin on lipid peroxidation and superoxide dismutase in adriamycin nephropathy in rats.

Cyclosporin A (CsA) was shown to reduce proteinuria in nephrotic syndrome, but its potential to increase lipid peroxidation may play a role in cyclosporin nephrotoxicity. The influence of cyclosporin treatment on the lipid peroxidation (assessed as malondialdehyde (MDA) in plasma and kidney homogenates using HPLC and reaction with thiobarbituric acid) and the activity of superoxide dismutase (SOD) in erythrocytes was studied in rats with nephrotic syndrome induced by single intravenous injection of adriamycin. Rats with nephrotic syndrome treated from the beginning with cyclosporin had lower proteinuria than untreated nephrotic rats. Free MDA in blood and kidney homogenates was significantly elevated in untreated nephrotic rats in comparison with controls. Activity of SOD in erythrocytes was significantly elevated in nephrotic rats treated with cyclosporin (113.40 +/- 34.31 mU/10(6) erythrocytes) in comparison with the control group (55.63 +/- 9.90 mU/10(6) erythrocytes, p < 0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10(6) erythrocytes, p < 0.01) and untreated nephrotic rats (65.07 +/- 17.49 mU/10(6) erythrocytes, p < 0.001). In conclusion, cyclosporin reduced proteinuria in rats with mild adriamycin nephropathy (similar to human minimal change disease). Cyclosporin also partially counteracted adriamycin-induced lipid peroxidation probably due to the stimulation of antioxidant enzyme SOD. The possible contribution of decreased lipid peroxidation to the antiproteinuric effect of cyclosporin deserves further study.

Lipid peroxidation and antioxidant enzymes in CAPD patients.

The mechanisms of free-radical injury include reactions with proteins, nucleic acids, and polysaccharides; and covalent binding to membrane components and initiation of lipid peroxidation. Cells have developed antioxidant defense to prevent free-radical injury including superoxide dismutase (SOD) and glutathione peroxidase (GPx). Significantly higher concentrations of total malondialdehyde (MDA) in plasma (1.22 +/- 0.42 vs. 0.64 +/- 0.22 micromol/L, p < 0.0001) as well as erythrocytes (2.56 +/- 1.28 vs. 1.03 +/- 0.44 micromol/L, p < 0.0001) of the CAPD patients were found when compared to the control group. The free MDA in plasma and the erythrocytes do not differ significantly in continuous ambulatory peritoneal dialysis (CAPD) patients and the control group. A significantly lower activity of GPx in erythrocytes of CAPD patients (17.85 +/- 2.63 U/g Hb vs. 23.26 +/- 3.61 U/g Hb, p < 0.0001) was found when compared to the control group, but the SOD activity in erythrocytes is not different (2272.36 +/- 579.92 U/g Hb vs. 2347.13 +/- 502.51 U/g Hg, NS). Our results show an increase of total MDA in erythrocytes and plasma. MDA is the product of lipid peroxidation with decreasing activity of GPx, which is capable of detoxifying peroxides. The activity of SOD did not change in CAPD patients. These results propose a possible role of free radicals with reduced antioxidant activity of GPx in CAPD patients and indicate that they could play some role in other pathological conditions such as atherogenesis and hemolysis.

Antioxidant enzymes and lipid peroxidation in patients with multiple myeloma.

Reactive oxygen species and other free radicals are known to be the mediators of phenotypic and genotypic changes that lead from mutation to neoplasia. The imbalance in tumor cell antioxidant defense mechanism can influence also the sensitivity to cytoreductive therapy. In erythrocytes it can result to hemolysis which is one of the pathogenetic mechanisms of anemia in cancer patients. Parameters of lipid peroxidation (malondialdehyde-MDA) and antioxidant enzymes here represented by superoxide dismutase (SOD) and glutathione peroxidase (GPx) in multiple myeloma (MM) have been investigated. Nine patients of various clinical stages and activities of the disease were studied. Significantly higher concentrations of total MDA in plasma (1.20 +/- 0.24 mumol/l vs. 0.64 +/- 0.22 mumol/l, p < 0.0001) as well as in erythrocytes (2.72 +/- 0.81 mumol/l vs. 1.03 +/- 0.44 mumol/l, p < 0.0001) were found comparing to the control group. The levels of free MDA in plasma (0.31 +/- 0.09 mumol/l vs. 0.49 +/- 0.17 mumol/l, p < 0.05) and in erythrocytes (0.29 +/- 0.20 mumol/l vs. 0.59 +/- 0.22 mumol/l, p < 0.001) were decreased in myeloma patients. Significantly lower activities of GPx (19.17 +/- 4.07 U/g Hb vs. 23.26 +/- 3.61 U/g Hb, p < 0.05) and SOD (1882.46 +/- 181.73 U/g Hb vs. 2347.13 +/- 502.51 U/g Hb, p < 0.05) in erythrocytes were found. We did not observe evident relationship between the concentration of MDA or the activities of SOD and GPx and either the stage of the disease, or the level and the type of paraprotein. These results propose possible role of free radicals with reduced antioxidant activities of SOD and GPx in multiple myeloma.

[Lipid peroxidation and activity of antioxidative enzymes in patients with multiple myeloma]. / Lipoperoxidace a aktivita antioxidacních enzymu u pacientu s mnohocetným myelomem.

BACKGROUNDS: Reactive oxygen species and other free radicals are known to be the mediators of phenotypic and genotypic changes that lead from mutation to neoplasia. The imbalance in tumor cell antioxidant defense mechanism can influence also the sensitivity to cytoreductive therapy. In erythrocytes it can results to hemolysis which is one of pathogenetic mechanisms of anemia in cancer patients. METHODS AND RESULTS: We investigated the parameters of lipid peroxidation (malondialdehyde-MDA) and antioxidant enzymes here represented by superoxide dismutase (SOD) and glutathione peroxidase (GPx) in multiple myeloma. Nine patients of various clinical stage and activity of disease were studied. A significant higher concentration of total MDA in plasma (1.20 +/- 0.24 mumol/l v.s. 0.64 +/- 0.22 mumol/l, p < 0.0001) as well as in erythrocytes (2.72 +/- 0.81 mumol/l v.s. 1.03 +/- 0.44 mumol/l, p < 0.0001) was found comparing to the control group. The levels of free MDA in plasma (0.31 +/- 0.09 mumol/l v.s. 0.49 +/- 0.17 mumol/l, p < 0.05) and in erythrocytes (0.29 +/- 0.20 mumol/l v.s. 0.59 +/- 0.22 mumol/l, p < 0.001) were decreased in myeloma patients. A significantly lower activity of GPx (19.17 +/- 4.07 U/g v.s. 23.26 +/- 3.61 U/g Hb, p < 0.05) and SOD (1882.46 +/- 181.73 U/g v.s. 2347.13 +/- 502.51 U/g Hb, p < 0.05) in erythrocytes were found. CONCLUSIONS: We didn't observe evident relationship between the concentration of MDA or activities of SOD and GPx and either the stage of disease or level and type of paraprotein. We can conclude, that higher concentration of total MDA as a parameter of lipid peroxidation, is significantly increased in patients with multiple myeloma. It could be consequence of impaired antioxidant defence. These results propose possible role of free radicals with reduced antioxidant activity of SOD and GPx in multiple myeloma. As we can consider the role of free radicals in pathogenesis of malignant proliferation, prognostic value and the change during the course of therapy should by studied.

Antioxidant enzymes--superoxide dismutase and glutathione peroxidase--in haemodialyzed patients.

The biological effect of oxygen-reactive species controlled by antioxidant mechanisms are exerted on the basis of antioxidant enzymes and substrates. In this study, the activities of antioxidant enzymes-superoxide dismutase (SOD) and glutathione peroxidase (GPx)-were determined in the erythrocytes of patients on regular haemodialysis treatment. The SOD activity was significantly lower (1,810.38 +/- 609.85 vs. 2,347.13 +/- 502.51 U/g haemoglobin, p < 0.05, or 70.71 +/- 11.50 vs. 100.13 +/- 24.28 mU/10(6) erythrocytes, p < 0.0001), as was the GPx activity (18.80 +/- 4.22 vs. 23.26 +/- 3.61 U/g haemoglobin, p < 0.01), when compared with the control group. A positive correlation between GPx activity and number of haemodialysis sessions was found (p = 0.0038), but no correlation between SOD activity and number of HD sessions. An inpaired antioxidant enzyme defence system, here represented by SOD and GPx levels, can potentiate injury caused by free radicals in haemodialysis patients.

[The role of oxygen radicals in the pathogenesis of glomerulonephritis]. / Uloha kyslíkových radikálu v patogenezi glomerulonefritid.

In the pathogenesis of glomerulonephritis, acute renal failure, pyelonephritis and other diseases of the kidneys oxygen radicals are involved. Some types of glomerulonephritis are characterized by infiltration of the glomeruli by neutrophils and monocytes which can form oxygen radicals (superoxide, hydrogen peroxide). The increased amount of cAMP in glomeruli can be due to oxygen radicals. Cyclic nucleotides modulate the inflammatory or immune response in glomerular disease and play a part in the action of local mediators of the inflammation. Oxygen radicals act as second messenger for the activation of cytokines via NF-kappaB transcription factor, they stimulate the formation of TNF-alpha, IL-1, IL-6 and influence the expression of monocyte-specific cytokines (CSF-1 and MCP-1). Radicals formed by the system myeloperoxidase--hydrogen peroxide--halogen derivatives activate proteolytic enzymes (proteinases) which break down collagen and other components of the extracellular matrix present in the basal membrane of glomeruli and in the mesangium. Oxygen radicals and proteinases can cause and amplify glomerular damage. Glucocorticoid administration leads to an increased activity of endogenous antioxidant enzymes in the glomerulus and reduced the of lipid peroxidation.

Lipid peroxidation and superoxide dismutase activity in umbilical and maternal blood.

Oxygenation of both mother and child tissues oscillate frequently during labour. We tested the lipid peroxidation caused by reactive oxygen species which are produced in consequence of tissue reoxygenation and the inactivation of these species by the maternal and newborn superoxide dismutase. Total malondialdehyde in concentrations (mean +/- SE) of 1.04 +/- 0.17, 1.57 +/- 0.22, 1.33 +/- 0.14 and 1.36 +/- 0.21 mumol/L was found in maternal plasma and red blood cells and newborn plasma and red blood cells, respectively, after uncomplicated deliveries and 4.93 +/- 1.34, 7.12 +/- 1.37, 4.77 +/- 1.29 and 7.37 +/- 1.51 mumol/L, respectively, after deliveries with clinical signs of foetal hypoxia. In newborns, erythrocyte superoxide dismutase activity reached only 82% of the maternal level (p < 0.05). The results indicate that the maternal and foetal antioxidant defence systems can be overloaded during deliveries with abnormal oxygenation, where increased lipid peroxidation occurred.

Xanthine oxidoreductase. Biochemical, biological and pathogenic functions.

Primary biochemical role of xanthine oxidoreductase (XOR, EC 1.1.1.204 and EC 1.1.3.22.) is the hydroxylation of hypoxathine and xanthine to form uric acid. This enzyme may produce very reactive oxygen forms which can be pathogenic. Although it is one of the longest known and most continuously studied enzymes, its biological function remains unclear. The review of these aspects is discussed in relation to the authors' experimental results.