The role of oxygen free radicals in isoniazid-induced hepatotoxicity

This report describes the glycosaminoglycans, collagen and elastin--composition of leiomyosarcoma. Studies were performed on leiomyosarcoma removed during surgery. The material was taken from 7 patients. Rearrangement of extracellular matrix in leiomyosarcoma has been found. There was an increase of total collagen content in comparison to control uterus. In both tissues type I collagen was found to be the predominant one. Both tissues, normal and neoplastic contain all known glycosaminoglycans types. Among them heparan sulphate was found to be the most abundant. A slight decrease in the content of this glycosaminoglycan was observed in leiomyosarcoma. A possible role of these alterations in tumour biology is discussed.     

Proinflammatory cytokines with free oxygen radicals in septic syndrome

In this paper authors presented the advantages of measuring the fibronectin levels in several diseases occurring during the pregnancy. They established usefulness of evaluating the fibronectin concentration in premature rupture of the amniotic membranes, preterm delivery, postdate pregnancy, preeclampsia, and intrauterine growth retardation.     

Effect of oxygen free radicals on myosin in muscle fibres

The Palmaz-Schatz stent delivery system (PS 153) and "bare" PS 204 stents are relatively high-profile, rigid devices that can be difficult to deliver to lesions beyond tortuous, irregular, or rigid proximal segments. Described herein is a method of mounting and shaping a Palmaz-Schatz stent on a low-profile balloon that provides a steerable, low-profile, and secure stent delivery system. Also described is the successful use of this method in four consecutive cases where Palmaz-Schatz stents could not be delivered to the lesion site due to severely angulated, irregular, or rigid proximal vessel segments.     

The role of active oxygen radicals in blood system reactions in inflammation

On the model of carrageenan-induced acute aseptic peritonitis in rats with using of alpha-tocopherol it is shown that the active oxygen metabolites increase granulomonocytopoiesis, leukocytosis and stimulation of blood neutrophils, accumulation and activation of neutrophils of an inflammatory focus, decrease accumulation and stimulation of monocytes of an inflammatory focus and thus they are pro-inflammatory modulators of the blood system's reactions.     

Dipyridamole and dilazep suppress oxygen radicals in puromycin aminonucleoside nephrosis rats

BACKGROUND: Reactive oxygen species (ROS) are involved in the pathophysiology of puromycin aminonucleoside (PAN) nephrosis. To elucidate further the role of radicals in PAN nephrosis and the to determine the particular radical species scavenged by dipyridamole (DPM) and dilazep (DZ), we applied chemiluminescence and electron spin resonance (ESR) techniques. METHODS: Chemiluminescence of glomeruli, which were isolated on day 7 from rats injected with 100 mg kg-1 PAN, was measured with or without scavengers. The inhibitory effects of DPM and DZ on hydroxyl radical adduct formation in the Fenton's reaction were evaluated using ESR. RESULTS: Chemiluminescence was greater in glomeruli from rats with PAN nephrosis than in the the glomeruli of control rats. This increase was suppressed by superoxide dismutase, catalase, dimethylthiourea and also by DPM and DZ. ESR indicated that DPM and DZ inhibited hydroxyl radical adduct formation with a second-order rate constant of 2.9 x 10(10) and 1.6 x 10(10) (mol L(-1) s(-1) respectively, similar to that of dimethylthiourea. CONCLUSION: DPM and DZ scavenge hydroxyl radicals, thereby alleviating PAN nephrosis.     

Effects of melatonin on lipid peroxidation induced by oxygen radicals

Osteoporosis is characterized by reduced bone mass and a deterioration of bone structure which results in an increased fracture risk. The purpose of this review is to evaluate structure analysis techniques in the diagnosis of osteoporosis. Several imaging techniques were applied to analyze trabecular bone, such as conventional radiography, high-resolution computed tomography (HR-CT) and high-resolution magnetic resonance imaging (HR-MRI). The best results were obtained using high-resolution tomographic techniques. The highest spatial resolutions in vivo were achieved using HR-MRI. These studies show that texture parameters and bone mineral density predict bone strength and osteoporotic fractures in a complementary fashion. Combining both techniques yields the best results in the diagnosis of osteoporosis.     

The role of oxygen radicals in the physiology and pathology of human sperm

Reactive oxygen species in low doses are necessary compound of sperm capacitation and hyperactivation. Superoxide anion, hydroxyl radical and hydrogen peroxide initiate sperm capacitation. The edding of antioxidant enzymes inhibits the spontaneous and induced sperm hyperactivation. The process of capacitation is accompanied with the superoxide anion production output by spermatozoa. High doses of reactive oxygen species block the sperm motility through the inhibition of ATP synthesis by the mitochondrial enzymes and cell membrane compounds injury.     

Ultraviolet radiation-induced production of superoxide radicals by selected antibiotics

The ability of certain drugs and chemicals to induce cutaneous phototoxicity and DNA damage has been attributed to free radical formation during photolysis. In this context we have observed that the synergistic action of commonly used antibiotics and ultraviolet radiation (UVR) exhibited strong superoxide radical (O2-) generation potential in the following order: benzylpenicillin > amphotericin > ampicillin > nystatin > spectinomycin > gentamicin. Commercially available penicillin, nystatin, ampicillin and gentamicin also generated O2- under similar conditions. The results suggest that due precaution are necessary to avoid UVR after the intake of photoreactive drugs.     

Polymorphonuclear leukocytes as a potential source of oxygen free radicals in myocardial infarction

The review of literature on the role of free radicals derived from neutrophils in coronary heart disease is presented. Polymorphonuclear leukocytes are the main source of oxygen derived free radicals. They contribute significantly to the pathogenesis of postischemic dysfunction reperfused myocardium.     

Ethanol stimulates the formation of free oxygen radicals in the brain of newborn rats

The possibility of free radicals effects in ethanol-induced teratogenesis was investigated by determining the production of reactive oxygen species (ROS) in the neonatal rat brain. Ethanol 33% was administered daily, by i.p. injection from day 8 of pregnancy to day 6-8 p.n. The presence of the lipid peroxidation process (indicating ROS formation) was determined by using a qualitative and quantitative analysis of malondialdehyde (MDA). An important increase of MDA was found suggesting the involvement of ROS in the pathogenetic mechanism of alcohol embryo- and fetopathy.     

Role of oxygen radicals generated by NADPH oxidase in apoptosis induced in human leukemia cells

We have used a human leukemia cell line that, after homologous recombination knockout of the gp91-phox subunit of the phagocyte respiratory-burst oxidase cytochrome b-558, mimics chronic granulomatous disease (X-CGD) to study the role of oxygen radicals in apoptosis. Camptothecin (CPT), a topoisomerase I inhibitor, induced significantly more apoptosis in PLB-985 cells than in X-CGD cells. Sensitivity to CPT was enhanced after neutrophilic differentiation, but was lost after monocytic differentiation. No difference between the two cell lines was observed after treatment with other apoptosis inducers, including etoposide, ultraviolet radiation, ionizing radiation, hydrogen peroxide, or 7-hydroxystaurosporine. After granulocytic differentiation of both cell lines, CPT still induced apoptosis, suggesting independence from replication in fully differentiated and growth-arrested cells. Pyrrolidine dithiocarbamate (an antioxidant inhibitor of NF-kappaB) and catalase partially inhibited CPT-induced DNA fragmentation in granulocytic-differentiated PLB-985 cells, but had no effect in X-CGD cells. Flow cytometry analysis revealed that reactive oxygen intermediates were generated in CPT-treated PLB-985 cells. These data indicate that oxygen radicals generated by NADPH oxidase may contribute directly or indirectly to CPT-induced apoptosis in human leukemia and in neutrophilic-differentiated cells.     

Direct measurement of oxygen free radicals during in utero hypoxia in the fetal guinea pig brain

The present study tested the hypothesis that maternal hypoxia induces oxygen free radical generation in the fetal guinea pig brain utilizing techniques of electron spin resonance spectroscopy and alpha-phenyl-tert-butyl nitrone (PBN) spin trapping. Pregnant guinea pigs of 60 days gestation were divided into normoxic and hypoxic groups and exposed to 21% or 7% oxygen for 60 min. Free radical generation was documented by measuring the signal of PBN spin adducts. Fluorescent compounds were determined as an index of lipid peroxidation and the activity of Na+,K+-ATPase was determined as an index of brain cell membrane function. Hypoxic fetal cerebral cortical tissue showed a significant increase in spin adducts (normoxic: 33.8+/-9.3 units/g tissue vs. hypoxic: 57.9+/-9.2 units/g tissue, p<0.01) and fluorescent compounds (normoxic: 0.639+/-0.054 microg quinine sulfate/g brain vs. 0.810+/-0.102 microg quinine sulfate/g brain, p<0.01) and a decrease in Na+,K+-ATPase activity (normoxic: 43.04+/-2.50 micromol Pi/mg protein/h vs. hypoxic: 33. 80+/-3.51 micromol Pi/mg protein/h, p<0.001). These results demonstrate an increased free radical generation during hypoxia in the fetal guinea pig brain. The spectral characteristics of the radicals were consistent with those of alkoxyl radicals. The increased level of fluorescent compounds and decreased activity of Na+,K+-ATPase indicated hypoxia induced brain cell membrane lipid peroxidation and dysfunction, respectively. These results directly demonstrate an increased oxygen free radical generation during hypoxia and suggest that hypoxia-induced increase in lipid peroxidation and decrease in membrane function, as indicated by a decrease in Na+,K+-ATPase activity, are consequences of increased free radicals. The nature of predominantly present alkoxyl radical indicates ongoing lipid peroxidation during hypoxia. The direct demonstration of oxygen free radical generation during hypoxia is the critical missing link in the mechanism of hypoxia-induced brain cell membrane dysfunction and damage.     

Effect of active oxygen radicals on protein and carbohydrate moieties of recombinant human erythropoietin

Our previous study showed that active oxygen radicals generated from a Fenton system and a xanthine plus xanthine oxidase system caused serious loss of in vivo bioactivity of recombinant human erythropoietin (EPO), a highly glycosylated protein. In the present study, we characterized the oxidative modifications to the protein and carbohydrate moiety of EPO, which lead to a reduction of its bioactivity. In vitro bioactivity was reduced when EPO was treated with oxygen radicals generated from a Fenton system in the presence of 0.016 mM H2O2, and the reduction was directly proportional to the loss of in vivo bioactivity. SDS-PAGE analysis showed that dimer formation and degradation was observed under more severe conditions (Fenton reaction with 0.16 mM H2O2). The tryptophan destruction was detected at 0.016 mM H2O2 and well correlated with the loss of in vitro bioactivity, whereas loss of other amino acids were occurred under more severe conditions. Treatment with the Fenton system did not result in any specific damage on the carbohydrate moiety of EPO, except a reduction of sialic acid content under severe condition. These results suggest that active oxygen radicals mainly react with the protein moiety rather than the carbohydrate moiety of EPO. Destruction of tryptophan residues is the most sensitive marker of oxidative damage to EPO, suggesting the importance of tryptophan in the active EPO structure. Deglycosylation of EPO caused an increased of susceptibility to oxygen radicals compared to intact EPO. The role of oligosaccharides in EPO may be to protect the protein structure from active oxygen radicals.     

Enhanced HBsAb production in pathogenesis of fulminant viral hepatitis type B

The possible importance of humoral immunity in the pathogenesis of fulminant hepatitis was investigated by comparing 17 patients with fulminant hepatitis type B with 20 patients with severe but non-fulminant disease. Hepatitis B surface antigen (HBsAg) was cleared from the serum significantly faster (P less than 0-001) in those with fulminant hepatitis, and in 41% anti-HBsAg (HBsAb) was detectable by radioimmunoassay (RIA) at presentation. In all 11 sera from patients with fulminant hepatitis that were examined by electron microscopy aggregates of HBsAg and HBsAb were seen. In contrast, HBsAb was never detected by RIA in those with non-fulminant hepatitis, and in only one serum specimen (5%) were aggregates seen on electron microscopy. A significant sex difference between fulminant and non-fulminant hepatitis was observed, 65% of patients with fulminant hepatitis but only 15% of patients with non-fulminant hepatitis being women (P less than 0-01). An enhanced production of HBsAb in fulminant hepatitis, by leading to free HBsAb in portal blood, may cause an Arthus reaction in the sinusoids of the liver with ensuing ischaemic necrosis of hepatocytes.     

Modulation of mouse cerebral Na+,K(+)-ATPase activity by oxygen free radicals

There is increasing evidence that oxygen free radicals (OFR) are involved in cerebral ischaemia-reperfusion injury, possibly via a modulation of Na+,K(+)-ATPase activity, one of the major membrane pumps responsible for ionic homeostasis. We measured OFR-mediated modulation of this enzymatic activity and examined the roles of lipid and/or protein alterations. Using mouse brain microsomes exposed to UV-C irradiation, our results show a good correlation between activity inhibition and lipoperoxidation estimated by PUFA loss as well as malondialdehyde production. The protective effect of thiourea (OH scavenger) and the lack of effect noted with DTT (thiol protector) suggest that the functionality of the Na+,K(+)-ATPase is altered by perturbation of membrane integrity rather than by a structural alteration of the protein itself.