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Biomedical subjects

C E Cross

Publications and source records attributed to C E Cross.

At least 73 records · Page 4Linked to original sources
PubMed1994

Interactions of peroxynitrite with human plasma and its constituents: oxidative damage and antioxidant depletion.

Endothelial cells and activated phagocytes produce both nitric oxide (.NO) and superoxide (O2.-), which react to form peroxynitrite. Peroxynitrite has been suggested to be directly cytotoxic and also to decompose into other toxic species. In order to understand the consequences of peroxynitrite generation in vivo, we examined its reaction with human blood plasma. Peroxynitrite decreased the total peroxyl-trapping capacity of plasma. In terms of specific antioxidants, addition of peroxynitrite to plasma leads to rapid oxidation of ascorbic acid, uric acid and plasma SH groups. The oxidation of plasma SH groups was enhanced in dialysed plasma and returned to control levels by the addition of physiological levels of bicarbonate. Evidence was found for formation of nitro-adducts to aromatic side chains in plasma proteins by peroxynitrite. Peroxynitrite also leads to depletion of ubiquinol and formation of traces of lipid hydroperoxides in plasma, although alpha-tocopherol levels were only slightly decreased. Peroxynitrite formation in human body fluids is likely to cause antioxidant depletion and oxidative damage.

Antioxidants↗
PubMed1994

Aromatic hydroxylation and nitration of phenylalanine and tyrosine by peroxynitrite. Evidence for hydroxyl radical production from peroxynitrite.

Peroxynitrite is a highly reactive species, generated from superoxide and nitric oxide. Some effects of peroxynitrite are ascribed to the molecule itself, but decomposition products of the protonated form, peroxynitrous acid, may account for much of its reactivity in biological systems. Suggested products include highly-reactive hydroxyl radicals, but thermodynamic calculations have been used to claim that free hydroxyl radicals cannot be formed from peroxynitrite. We utilized aromatic hydroxylation of phenylalanine as a specific detector of hydroxyl radicals, and found that incubation of phenylalanine with peroxynitrite leads to a small amount of p-, m- and o-tyrosine, specific products of attack by this radical. Products of nitration of phenylalanine and tyrosine were also detected, as was dityrosine. Peroxynitrite decomposition generates several reactive species, including some that can nitrate aromatic rings. Formation of nitro-aromatic compounds may be a useful marker of peroxynitrite generation in biological systems.

Hydroxyl Radical↗
PubMed1994

Oxidants, antioxidants, and respiratory tract lining fluids.

Respiratory tract lining fluids (RTLFs) are a heterogeneous group of substances covering the respiratory tract epithelial cells (RTECs) from nasal mucosa to alveoli. Antioxidant contained in the RTLFs can be expected to provide an initial defense against inhaled environmental toxins. The major antioxidants in RTLF include mucin, uric acid, protein (largely albumin), ascorbic acid, and reduced glutathione (GSH). RTLF antioxidants can be augmented by such processes as transudation/exudation of plasma constituents; RTEC secretory processes, including glandular mucus secretion; and cellular antioxidants derived from lysis of RTECs and of inflammatory cells. The antioxidant composition of RTLFs and their role in modulating normal and pathophysiologic RTEC functions under conditions of oxidative stress are yet to be fully characterized.

Animals↗
PubMed1994

Oxygen-derived species: their relation to human disease and environmental stress.

Free radicals and other reactive oxygen species (ROS) are constantly formed in the human body, often for useful metabolic purposes. Antioxidant defenses protect against them, but these defenses are not completely adequate, and systems that repair damage by ROS are also necessary. Mild oxidative stress often induces antioxidant defense enzymes, but severe stress can cause oxidative damage to lipids, proteins, and DNA within cells, leading to such events as DNA strand breakage and disruption of calcium ion metabolism. Oxidative stress can result from exposure to toxic agents, and by the process of tissue injury itself. Ozone, oxides of nitrogen, and cigarette smoke can cause oxidative damage; but the molecular targets that they damage may not be the same.

Air Pollution↗
PubMed1994

Lipoic and dihydrolipoic acids as antioxidants. A critical evaluation.

A detailed evaluation of the antioxidant and pro-oxidant properties of lipoic acid (LA) and dihydrolipoic acid (DHLA) was performed. Both compounds are powerful scavengers of hypochlorous acid, able to protect alpha 1-antiproteinase against inactivation by HOCl. LA was a powerful scavenger of hydroxyl radicals (OH.) and could inhibit both iron-dependent OH. generation and peroxidation of ox-brain phospholipid liposomes in the presence of FeCl3-ascorbate, presumably by binding iron ions and rendering them redox-inactive. By contrast, DHLA accelerated iron-dependent OH. generation and lipid peroxidation, probably by reducing Fe3+ to Fe2+. LA inhibited this pro-oxidant action of DHLA. However, DHLA did not accelerate DNA degradation by a ferric bleomycin complex and slightly inhibited peroxidation of arachidonic acid by the myoglobin-H2O2 system. Under certain circumstances, DHLA accelerated the loss of activity of alpha-antiproteinase exposed to ionizing radiation under a N2O/O2 atmosphere and also the loss of creatine kinase activity in human plasma exposed to gas-phase cigarette smoke. Neither LA nor DHLA reacted with superoxide radical (O.2-) or H2O2 at significant rates, but both were good scavengers of trichloromethylperoxyl radical (CCl3O2.). We conclude that LA and DHLA have powerful antioxidant properties. However, DHLA can also exert pro-oxidant properties, both by its iron ion-reducing ability and probably by its ability to generate reactive sulphur-containing radicals that can damage certain proteins, such as alpha 1-antiproteinase and creatine kinase.

Animals↗
PubMed1994

Interactions of human blood plasma with hydrogen peroxide and hypochlorous acid.

Activated neutrophils produce both hydrogen peroxide (H2O2) and hypochlorous acid (HOCl). Previous work has shown that HOCl depletes antioxidants, modifies proteins, and forms fatty acid chlorohydrins but does not cause significant lipid peroxidation in human plasma. Because activated phagocytes have been claimed to stimulate lipid peroxidation in plasma, we examined the effects of H2O2 and HOCl alone and in combination on plasma constituents. Hydrogen peroxide at concentrations below 0.5 mmol/L had little effect, but 1 to 2 mmol/L H2O2 caused loss of ascorbic acid and protein thiol groups, an effect potentiated by preincubation of the plasma with sodium azide to inhibit catalase. H2O2 caused no detectable lipid peroxidation or loss of alpha-tocopherol in plasma, but some depletion of ubiquinol occurred. The combination of HOCl and H2O2 caused more lipid peroxidation than either agent alone. Peroxidation was not inhibited by the metal chelators ethylenediaminetetraacetic acid and deferoxamine or by the singlet O2/hydroxyl radical scavenger histidine. We hypothesize that the phagocyte-derived H2O2 and HOCl could interact in the microenvironment of the activated leukocyte to induce lipid peroxidation of plasma lipoproteins or cell membranes (or both).

Antioxidants↗
PubMed1994

Aldehyde-induced protein modifications in human plasma: protection by glutathione and dihydrolipoic acid.

Exposure of human plasma to gas phase cigarette smoke (CS) produces a depletion of ascorbic acid, peroxidation of lipids (Frei et al. Biochem J 1991; 277: 133-8), and protein modification (as measured by protein carbonyl accumulation and loss of sulfhydryl groups) (Reznick et al. Biochem J 1992; 286: 607-11). CS contains both saturated and unsaturated aldehydes. The contribution of these aldehydes to the damaging effects of CS on human plasma was investigated. Aldehydes present in CS did not cause a depletion of plasma antioxidants such as ascorbic acid or alpha-tocopherol and did not induce plasma lipid peroxidation. Aldehydes decreased plasma protein sulfhydryl concentrations but increased protein carbonyls. The thiols glutathione and dihydrolipoic acid had a significant effect in reducing aldehyde-induced protein modifications.

Adult↗
PubMed1993

Reduction of the surface-tension-lowering ability of surfactant after exposure to hypochlorous acid.

The reactive species hypochlorous acid (HOCl/OCl-) is a major product of the respiratory burst in activated neutrophils. We studied the effects of HOCl/OCl- on human surfactant and upon surfactants Survanta, KL4 and Exosurf, utilizing a pulsating surfactometer for measuring surface tension. HOCl/OCl- induced a marked dose-dependent decrease in the surface-tension-lowering activity of human surfactant. The surfactant containing surfactant proteins B and C (Survanta) was less sensitive; however, synthetic surfactants with or without peptides were not affected by HOCl/OCl- (KL4, Exosurf). Ascorbic acid and GSH protected human surfactant against inactivation by HOCl/OC1-. We suggest that HOCl/OCl- produced by activated phagocytes in the alveolar compartment of the lung could damage endogenous surfactant and affect the function of exogenously administered natural or other surfactants, especially if ascorbic acid and GSH levels in the lung lining fluids are subnormal, as is known to be the case in some inflammatory lung diseases.

Amniotic Fluid↗
PubMed1993

Cigarette smoke oxidation of human plasma constituents.

In vitro exposure of fresh human plasma to cigarette smoke (CS) was used as a model for reactions that could be occurring in CS-exposed respiratory tract lining fluids (RTLFs) and lung parenchyma. The central focus of this model was to characterize the consumption of endogenous plasma antioxidants in relationship to the appearance of oxidized proteins and lipids as a consequence of exposure to CS, or to aldehydes present in CS. The amelioration of CS-induced protein and lipid oxidation in plasma by the addition of selective exogenous antioxidants was also assessed. We found that: (i) exposure of human plasma to gas phase CS causes both lipid peroxidation and protein oxidation, and endogenous ascorbic acid protects against lipid, but not protein, oxidation; (ii) whole CS causes protein oxidation, but does not induce lipid peroxidation; (iii) addition to plasma of aldehydes known to be present in CS causes protein damage, but does not induce either lipid peroxidation or oxidation of ascorbic acid; and (iv) exogenously added dihydrolipoic acid (DHLA) preserves ascorbic acid levels in plasma exposed to the gas phase of CS, and protects, to some extent, against lipid peroxidation; DHLA also protects against protein oxidation, whereas added glutathione (GSH) only protects against protein, but not lipid, oxidation.

Adult↗
PubMed1993

Elevated levels of serum mucin-associated antigen in adult patients with cystic fibrosis.

Previous studies using the CA 19-9 antibody have demonstrated that serum mucin levels in patients with cystic fibrosis (CF) are elevated and that the degree of elevation relates to the age of the patient and possibly to his or her clinical status. However, CA 19-9 only recognizes the mucin-associated blood group sialyl Le(a+) antigen, so mucin levels cannot be measured in patients without Lewis antigens. The present study used the 17B1 monoclonal antibody to measure serum mucin levels in normal subjects, and in patients with CF, patients with chronic obstructive pulmonary disease (COPD), and patients with lung transplants. Serum mucin levels were 25 ng/ml (+/- 1 SEM, n = 8) in normal subjects, 13,853 ng/ml (+/- 1,281, n = 25) in patients with CF, and 25.5 ng/ml (+/- 1.9, n = 17) in patients with COPD. Patients with CF who were sialyl Le(a-b-) also had elevated serum mucin levels (715 +/- 152, n = 2). Serum mucin levels of six lung transplant recipients with CF were elevated compared with those in normal subjects (4,621 +/- 765 ng/ml), but they were not different from serum mucin levels in six lung transplant recipients without CF (5,307 +/- 1.677 ng/ml). Preliminary characterization of the serum mucin antigen showed that: (1) in CF sera, the antigen is polydisperse and smaller than the antigen in normal sera; (2) the mucin antigen is distinct from ABO blood group antigens. Serum mucin levels may be a useful marker to follow a specific patient's response to therapy.

ABO Blood-Group System↗
PubMed1993

Oxidation of biologic molecules by ozone: the effect of pH.

Ozone (O3) is a powerfully oxidizing pollutant gas. Its toxic effects to animals appear to be worsened by coexposures to acid-generating compounds such as oxides of nitrogen and sulfur. Ozone (16 ppm) oxidizes ascorbic acid and uric acid (two important antioxidants in lung lining fluids) at equal rates at pH 5.0 or pH 7.4. Loss of intrinsic fluorescence and formation of carbonyls in albumin exposed to O3 are similar at both pH values. However, albumin-SH groups are lost much faster on exposure to O3 at pH 7.4 than at acidic pH values. A similar slower rate of -SH group disappearance at acidic pH is seen when cysteine or reduced glutathione are exposed to O3. We suggest that the ability of reduced glutathione, albumin, and other proteins containing -SH groups to scavenge O3 in the respiratory tract is impaired at low pH and that this effect could contribute to the aggravation of O3 toxicity.

Albumins↗