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Antioxidatives are widely used and recommended in common clinical praxis, even though they may have negative impact on our health under some circumstances (i.e. N-acetylcysteine, vitamin E, risk of lung cancer etc.). Our aim was to evaluate the role of exogenous scavengers in prevention of induced oxidative stress in rodents. Male ICR mice were used and acute hypoglycaemia was induced with insulin. The mice were randomized into eight experimental groups, either pretreated by vitamin C or vitamin E or combinations with respective vehicles. Total malondialdehyde (MDA), superoxide dismutase (SOD), and selenium-dependent glutathione peroxidase (GSHPx) activity were measured in brain tissue samples. ANOVA with a post-hoc Duncan or Turkey׳s tests were used for statistical evaluation. A statistically significant increase in brain MDA was observed after insulin-induced severe hypoglycaemia relative to normoglycaemia. Animals pretreated with vitamins, both in monotherapy and in combination (both P

summary Background & aims: Recent epidemiological studies have supported the idea that food rich in plant bioactive compounds and polyphenols in particular may exert beneficial effects toward human health. One of the foodstuffs widely distributed in the human diet is red wine, a strong antioxidant that contains many bioactive compounds, such as: polyphenols, minerals, and vitamins. The objective of this study was therefore to assess the antioxidant capacity, total phenolics, selected vitamin and mineral content in red wine samples and also to elucidate the existence of a possible relationship between grape variety and all constituents of wines as mentioned above. Methods: The set of 10 red wines, six of Cabernet Sauvignon and four of Merlot was subjected to the study. In all samples total antioxidant capacity was measured by Trolox equivalent antioxidant capacity (TEAC) assay and the Ferric reducing ability of plasma (FRAP) assay simultaneously with total phenolic content, selected minerals and essential vitamins. Results: Both antioxidant capacity and phenolic content were higher in Cabernet Sauvignon wines compared to Merlot. The total antioxidant capacity correlated positively with total phenolic content (r ¼ 0.88, p < 0.001 for TEAC assay and r ¼ 0.89, p < 0.001 for FRAP assay respectively), while a significant relationship among antioxidant capacity, selected minerals and vitamins was not observed. Among the nine minerals analyzed, potassium, zinc and magnesium were the most abundant elements distributed throughout all wine samples. Our results suggest that antioxidant capacity is dependent mainly on total phenolics. Grape variety largely determines such components as phenolic content, antioxidant capacity and mineral content with the exception of vitamins.

Apocynin is a naturally occurring methoxy-substituted catechol, experimentally used as an inhibitor of NADPH oxidase. Since it acts as a potent inhibitor in studies with neutrophils and macrophages, no inhibitory effect can often be found in non-phagocyte cells. In our experiments, apocynin even stimulated reactive oxygen species (ROS) production by vascular fibroblasts. Even when added to macrophages, apocynin initially caused an increase in ROS production. The inhibition of ROS formation followed, suggesting that in the presence of leukocyte myeloperoxidase and hydrogen peroxide, apocynin is converted to another compound. Apocynin pre-activated with H2O2 and horseradish peroxidase (HRP) inhibited ROS production immediately. In non-phagocytes, apocynin stimulated ROS production and no inhibition was observed even after 60 min. Apocynin treated with H2O2 and HRP, however, decreased ROS production in the same manner as in macrophages. The stimulatory effect on ROS production can be abolished by tiron and superoxide dismutase (SOD), suggesting that superoxide was the produced species. The effect of apocynin was inhibited by diphenylene iodinium (DPI), a non-scavenging NADPH oxidase inhibitor. It can be summarized that apocynin stimulates cell superoxide production. In the presence of peroxidase and hydrogen peroxide, however, it is converted into another compound that acts as an inhibitor of superoxide production. It strongly suggests that under conditions in vivo, apocynin can have opposite effects on phagocytes and non-phagocyte cells. It acts as an inhibitor of phagocyte NADPH oxidase but also as a ROS production stimulator in non-phagocyte cells.

The activities of superoxide dismutase, glutathione peroxidase (GPX) and catalase—the enzymatic scavengers of reactive oxygen species and the activities of xanthine oxidoreductase and xanthine oxidase, an enzyme known to generate reactive oxygen species, were studied in the corneas of normal rabbit eyes of various ages (1 month—young eyes; 4–9.5 months—young adult eyes; 2.0–2.75 years—middle aged eyes; 3.0–5.0 years—aged eyes). The activities of GPX, superoxide dismutase, xanthine oxidoreductase and xanthine oxidase were investigated biochemically in the scraped corneal epithelium. Catalase activity was detected histochemically in the corneal epithelium and endothelium. The results show that young corneas revealed lower activities of all the antioxidant enzymes investigated than did young adult corneas, in which enzymatic activities reached their maximum. In middle-aged corneas, GPX and catalase activities remained approximately at the same levels as seen in young adult corneas, whereas superoxide dismutase activity was decreased. In aged corneas, the activities of all antioxidant enzymes were dramatically decreased or even lost (catalase activity in the corneal endothelium). In contrast, xanthine oxidoreductase activity only slightly decreased with age and the xanthine oxidase proportion of total xanthine oxidoreductase remained unchanged. GPX, superoxide dismutase and catalase are important antioxidant enzymes protecting the cornea against the oxidative damage. Because the activities of these enzymes are lower in young animals and greatly reduced in aged animals, it is suggested that young and particularly aged corneas might be more susceptible to oxidative stress than are young adult corneas. This presumption is supported by the fact that the activities of prooxidant enzymes (xanthine oxidoreductase/xanthine oxidase) are only slightly decreased in aged corneas as compared to young adult corneas so that some imbalance between antioxidant and prooxidant enzymes exists already in the normal aged corneas.

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.

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 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, p0.05, or 70.71 +/- 11.50 vs. 100.13 +/- 24.28 mU/10(6) erythrocytes, p0.0001), as was the GPx activity (18.80 +/- 4.22 vs. 23.26 +/- 3.61 U/g haemoglobin, p0.01), 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.

Today, World Wide Web technology provides many opportunities in the disclosure of electronic learning and teaching content. The MEFANET project (MEdical FAculties NETwork) has initiated international, effective and open cooperation among all Czech and Slovak medical faculties in the medical education fields. This paper introduces the original MEFANET educational web portal platform. Its main aim is to present the unique collaborative environment, which combines the sharing of electronic educational resources with the use tools for their quality evaluation. It is in fact a complex e-publishing system, which consists of ten standalone portal instances and one central gateway. The fundamental principles of the developed system and used technologies are reported here, as well as procedures of a new multidimensional quality assessment.

All living organisms are connected to the environment by some kind of chemical recognition and signal generation system. For instance, we make use of our senses: olfaction, sight, touch, taste and hearing to recognize either molecules (olfaction and taste) or physical stimuli (photons, sound waves, pressure, etc.). Likewise, each individual cell in unicellular or multicellular organisms senses stimuli from its surrounding environment (extracellular fluids, other cells and so on) through receptors on the cell surface.

Pregnancy is a period when increased oxidative stress can be expected. We have focused especially on oxidative stress and inflammation in the period of pregnancy, when prenatal screening is usually performed. We determined advanced oxidation protein products (AOPPs), C-reactive protein (CRP) and anticardiolipin antibodies (ACA) IgG and IgM levels in the serum of 86 pregnant women in the 1st trimester and 102 pregnant women in the 2nd trimester. AOPP levels in the maternal serum of pregnant women were significantly higher in the 1st and 2nd trimesters than they were in that of non-pregnant women (p

It is generally accepted that the balance between the formation and inactivation of reactive oxygen species may be abolished within the perinatal period, as a consequence of rapid changes in tissue oxygen concentration and the development of antioxidant defence enzyme activities. We studied the ontogeny of the antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GPx) in fetal blood samples. The activity of SOD in fetal erythrocytes taken in the 17th gestational week was the same as that in erythrocytes of healthy blood donors. On the other hand, GPx activity was significantly lower between the 17th and 25th gestational week and at the time of delivery, compared with the healthy adult control. Our results suggest that the supposed underdevelopment of the antioxidant system in the lungs or in the other organs of premature infants cannot be monitored by SOD and GPx activities in erythrocytes, because these reach adult levels before the 17th week for SOD and from the 26th to the 35th gestational week for GPx, with lower levels from the 17th to the 25th week and at term.

As a result of oxidative and carbonyl stress, advanced glycation end products (AGEs) are involved in the pathogenesis of severe and frequent diseases and their fatal vascular/cardiovascular complications, i.e. diabetes mellitus and its complications (nephropathy, angiopathy, neuropathy and retinopathy, renal failure and uremic and dialysis-associated complications), atherosclerosis and dialysis-related amyloidosis, neurodegenerative diseases, and rheumatoid arthritis. They are formed via non-enzymatic glycation which is specifically enhanced through the presence of oxidative and carbonyl stress, and their ability to form glycoxidation products in peptide and protein structures finally modulating or inducing biological reactivity. Food can be another source of AGEs; however, high serum AGEs in hemodialysis patients might reflect nutritional status better. Several methods of renal replacement therapy have been studied in connection with the AGE removal, but unfortunately the possibilities are still unsatisfactory even if high flux dialysis, hemofiltration, or hemodiafiltration give better results than conventional low flux dialysis. AGEs are currently being studied in the patients on peritoneal dialysis as their precursors can be formed in the dialysis fluid. AGEs can cause damage to the peritoneum and so a loss of ultrafiltration capacity. Many compounds give promising results in AGE inhibition (inhibition of formation of AGEs, inhibition of their action or degradation of AGEs), are tested for these properties, and eventually undergo clinical studies (e.g. aminoguanidine, OPB-9195, pyridoxamine, antioxidants, N-phenacylthiazolium bromide, antihypertensive drugs, angiotensin-converting enzyme inhibitors and angiotensin II receptor-1 antagonists).

Alcohol-induced oxidative stress is linked to the metabolism of ethanol. Three metabolic pathways of ethanol have been described in the human body so far. They involve the following enzymes: alcohol dehydrogenase, microsomal ethanol oxidation system (MEOS) and catalase. Each of these pathways could produce free radicals which affect the antioxidant system. Ethanol per se, hyperlactacidemia and elevated NADH increase xanthine oxidase activity, which results in the production of superoxide. Lipid peroxidation and superoxide production correlate with the amount of cytochrome P450 2E1. MEOS aggravates the oxidative stress directly as well as indirectly by impairing the defense systems. Hydroxyethyl radicals are probably involved in the alkylation of hepatic proteins. Nitric oxide (NO) is one of the key factors contributing to the vessel wall homeostasis, an important mediator of the vascular tone and neuronal transduction, and has cytotoxic effects. Stable metabolites--nitrites and nitrates--were increased in alcoholics (34.3 +/- 2.6 vs. 22.7 +/- 1.2 micromol/l, p0.001). High NO concentration could be discussed for its excitotoxicity and may be linked to cytotoxicity in neurons, glia and myelin. Formation of NO has been linked to an increased preference for and tolerance to alcohol in recent studies. Increased NO biosynthesis also via inducible NO synthase (NOS, chronic stimulation) may contribute to platelet and endothelial dysfunctions. Comparison of chronically ethanol-fed rats and controls demonstrates that exposure to ethanol causes a decrease in NADPH diaphorase activity (neuronal NOS) in neurons and fibers of the cerebellar cortex and superior colliculus (stratum griseum superficiale and intermedium) in rats. These changes in the highly organized structure contribute to the motor disturbances, which are associated with alcohol abuse. Antiphospholipid antibodies (APA) in alcoholic patients seem to reflect membrane lesions, impairment of immunological reactivity, liver disease progression, and they correlate significantly with the disease severity. The low-density lipoprotein (LDL) oxidation is supposed to be one of the most important pathogenic mechanisms of atherogenesis, and antibodies against oxidized LDL (oxLDL) are some kind of epiphenomenon of this process. We studied IgG oxLDL and four APA (anticardiolipin, antiphosphatidylserine, antiphosphatidylethanolamine and antiphosphatidylcholine antibodies). The IgG oxLDL (406.4 +/- 52.5 vs. 499.9 +/- 52.5 mU/ml) was not affected in alcoholic patients, but oxLDL was higher (71.6 +/- 4.1 vs. 44.2 +/- 2.7 micromol/l, p0.001). The prevalence of studied APA in alcoholics with mildly affected liver function was higher than in controls, but not significantly. On the contrary, changes of autoantibodies to IgG oxLDL revealed a wide range of IgG oxLDL titers in a healthy population. These parameters do not appear to be very promising for the evaluation of the risk of atherosclerosis. Free radicals increase the oxidative modification of LDL. This is one of the most important mechanisms, which increases cardiovascular risk in chronic alcoholic patients. Important enzymatic antioxidant systems - superoxide dismutase and glutathione peroxidase - are decreased in alcoholics. We did not find any changes of serum retinol and tocopherol concentrations in alcoholics, and blood and plasma selenium and copper levels were unchanged as well. Only the zinc concentration was decreased in plasma. It could be related to the impairment of the immune system in alcoholics. Measurement of these parameters in blood compartments does not seem to indicate a possible organ, e.g. liver deficiency.

Nitnc oxide synthase (NOS), the enzyme with reduced nicotinamide-adenine dinucleotide phosphate (NADPH)-diaphorase activity, generates nitnc oxide (NO) which is an important bioregulatory molecule in the nervous, immune, and cardiovascular systems. NOS is linked to non- adrenergic non-cholinergic (NANC) neuronal pathways and modulation of the yV-methyl-D-aspartate receptors, yet its modification by ethanol has been little explored. A possible modification by chronic ethanol administration of activity and/or localization of NADPH-diaphor ase (NO-synthase) in rat brain may thus provide the pathogenic basis of alcohol-induc ed brain injury. When female Wistar rats were treated chronically with ethanol for 50 days, the NADPH-diaphorase staining of granular neurons and neurons located in the molecular layer of the cerebral cortex was significantly reduced. Chronic ethanol consumption led to a significant reduction in NADPH-diaphorase staining in the superficial layers of the superior colliculus. The number of NADPH-diaphor ase-positive neurons was significantly reduced (P < 0.001) in the stratum zonale and stratum griseum superficiale (by 42 3—65 6% of control values). This could alter synaptic processes in the highly organized structures involved in oculomotor and somatic motor coordination and thus contribute to the motor disturbances which are associated with alcohol abuse.

Tumor growth can often induce signs of oxidative stress in host organism. To assess the situation as for melanoma, the oxidative stress markers (specific malondialdehyde-thiobarbituric acid complexes: MDA-TBA; and less specific thiobarbituric acid reactive substances: TBARS) were measured in sera, liver and tumors of B16- and Cloudman S91- bearing mice and compared to those of control animals. The MDA-TBA levels (unlike TBARS) in the sera and liver of melanoma-bearing mice were significantly lower compared to controls. In addition, a significantly higher concentration of vitamin E was found in the blood and liver of both melanoma models compared to controls. Contrary to expectation, it appears that melanoma-bearing mice are able to suppress the level of lipid peroxidation. The free radical balance in melanoma-bearing hosts is unique and differs from other tumor types. This should be taken into consideration when designing a human melanoma therapy.

The acute administration of ethanol by gastric catheter significantly increases the plasma xanthine oxidase activity in both rats and hamsters without changing other enzyme activities--alanine aminotransferase and aspartate aminotransferase. The plasma xanthine oxidase level seems to be a sensitive marker of liver damage. Its higher activity due to the acute ethanol intoxication may have an impact on ethanol organ damage.

BACKGROUND Oxidative stress can potentiate atherogenesis via modification of biological structures and formation of new compounds, e.g. advanced glycation end products (AGEs) and advanced oxidation protein products (AOPP). The aim of the study was to determine AGEs and AOPP in patients with atherosclerosis, effect of statin therapy and relationship to parameters of lipid metabolism. METHODS AND RESULTS AGEs (carboxymethyllysine - ELISA and fluorescent AGEs - spectrofluorimetry) and AOPP (spectrophotometry) were assessed in 42 patients with atherosclerosis and 21 healthy controls. AGEs are significantly elevated in patients with atherosclerosis in comparison with healthy subjects (carboxymethyllysine 9.02+/-1.66 microg/g prot. vs 7.52+/-1.18 microg/g prot., p

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, p0.0001) as well as erythrocytes (2.56 +/- 1.28 vs. 1.03 +/- 0.44 micromol/L, p0.0001) 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, p0.0001) 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.

Initial reports on antiproteinuric effect of pefloxacine in small groups of patients with minimal-change nephropathy (MCN) and focal and segmental glomerulosclerosis (FSGS) have not been confirmed in other papers. To assess its antiproteinuric effect in experimental animals we administered pefloxacine to rats with adriamycin nephropathy showing morphological changes resembling human minimal-change disease or focal segmental glomerulosclerosis, and clinically with full-blown nephrotic syndrome. Pefloxacine treatment was at least partially effective in preventing further increase of proteinuria in rats with adriamycin nephropathy. The mechanism of this effect remains unclear and deserves further studies concentrating on the glomerular cytokine network and glomerular production of reactive oxygen species.

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.

Alcoholic liver disease may be frequently complicated by mesangial proliferation with the deposition of IgA in glomeruli and glomerulosclerosis, but these glomerular lesions are usually mild and without greater impact on renal function. To evaluate the putative role of ethanol in glomerular pathology we studied the influence of chronic ethanol administration on the development of experimental adriamycin nephropathy in rats. Nephrotic syndrome was induced by a single i.v. dose of adriamycin (5 mg/kg body wt) both in rats given ethanol at a dose of 4 g/day for 3 months and control rats given standard chow. Further controls on both diets without adriamycin administration were also studied. Blood and urine were examined before and 3 and 6 weeks after adriamycin administration. All rats were killed and examined histologically 6 weeks after adriamycin administration. Ethanol fed nephrotic rats were more catabolic than control nephrotic rats (with higher free fatty acids, lower glycaemia, higher urea with similar creatinine) and had lower proteinuria (0.55 +/- 0.34 versus 5.79 +/- 3.15 g of protein/nmol of creatinine, P < 0.05), higher albuminaemia (5.41 +/- 2.62 versus 1.92 +/- 1.94 g/l, P < 0.01), lower plasma cholesterol (6.54 +/- 2.6 versus 10.57 +/- 2.92 mmol/l, P < 0.01) and triglycerides. The development of nephrotic syndrome and renal morphological changes after adriamycin administration in rats seemed to be ameliorated, or at least delayed by chronic ethanol feeding with much milder and focal glomerulosclerosis as compared with more severe and diffuse glomerulosclerosis in control nephrotic animals. The mechanism of this effect of chronic ethanol feeding remains to be elucidated.(ABSTRACT TRUNCATED AT 250 WORDS)

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, p0.001), rats treated with cyclosporin (65.7 +/- 17.49 mU/10(6) erythrocytes, p0.01) and untreated nephrotic rats (65.07 +/- 17.49 mU/10(6) erythrocytes, p0.001). 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.