Biomedical subjects

R Stocker

Publications and source records attributed to R Stocker.

192 records · Page 11Linked to original sources

PubMed1987

Antioxidant activity of albumin-bound bilirubin.

Bilirubin, when bound to human albumin and at concentrations present in normal human plasma, protects albumin-bound linoleic acid from peroxyl radical-induced oxidation in vitro. Initially, albumin-bound bilirubin (Alb-BR) is oxidized at the same rate as peroxyl radicals are formed and biliverdin is produced stoichiometrically as the oxidation product. On an equimolar basis, Alb-BR successfully competes with uric acid for peroxyl radicals but is less efficient in scavenging these radicals than vitamin C. These results show that 1 mol of Alb-BR can scavenge 2 mol of peroxyl radicals and that small amounts of plasma bilirubin are sufficient to prevent oxidation of albumin-bound fatty acids as well as of the protein itself. The data indicate a role for Alb-BR as a physiological antioxidant in plasma and the extravascular space.

Antioxidants↗

PubMed1987

Potential role of conjugated bilirubin and copper in the metabolism of lipid peroxides in bile.

Conjugated bilirubin and copper ions at their physiological concentrations in bile may play an important role in hydroperoxide and other detoxification. Conjugated bilirubin may also be an important chain-breaking antioxidant preventing lipid peroxidation. Bilirubin ditaurine (BR-DT), a water-soluble model compound of conjugated bilirubin, completely prevents the peroxyl radical-induced oxidation of phosphatidylcholine in either multilamellar liposomes or micelles. This antioxidant activity is associated with the bilirubin moiety of BR-DT, since taurine alone is inefficient in scavenging peroxyl radicals. The number of peroxyl radicals trapped per molecule of BR-DT is 1.9, compared to 4.7 trapped per molecule of biliverdin, the water-soluble physiological precursor of bilirubin. Peroxyl radical-induced oxidation of BR-DT results in a spectral shift in maximal absorbance toward shorter wavelengths; biliverdin is not formed as a major oxidation product. BR-DT, but neither taurine nor biliverdin, greatly accelerates the cupric ion-catalyzed decomposition of linoleic acid hydroperoxide. In the presence of ferric ion, BR-DT shows no lipid hydroperoxide-degrading activity. Addition of cupric ion to BR-DT results in formation of a complex with spectral features similar to that of a biliverdin-cupric ion complex, indicating that BR-DT and cupric ion undergo redox reactions.

Bile↗

PubMed1986

Possible mechanisms responsible for the increased ascorbic acid content of Plasmodium vinckei-infected mouse erythrocytes.

The possible mechanisms underlying the acquisition of an increased ascorbic acid content by mouse erythrocytes containing the malarial parasite Plasmodium vinckei were investigated. Ascorbic acid was taken up readily by parasitized red blood cells but not by controls, whilst its partly oxidized form, dehydroascorbic acid, entered both. The uptake of both ascorbic acid and dehydroascorbic acid into erythrocytes was increased as a result of malarial infection. Lysates prepared from parasitized red blood cells reduced exogenous dehydroascorbic acid to ascorbic acid at a higher rate than control red blood cell lysates; this difference was abolished following dialysis of the lysates, a process which removes endogenous reduced glutathione (GSH). The rates of chemical and enzymatic reduction of dehydroascorbic acid to ascorbic acid by GSH were of similar magnitude, thus calling into question the existence of a specific dehydroascorbate reductase in erythrocytes and parasites. These observations suggest that the increased uptake of dehydroascorbic acid into parasitized red blood cells may be a result of enhanced dehydroascorbate-reducing capacity, whilst the presence of the parasite induces a selective increase in the permeability of the erythrocyte plasma membrane to ascorbic acid. The endogenous ascorbic acid content of livers obtained from infected mice was 55% below the normal concentration and its relative rate of destruction during incubation in vitro was enhanced in comparison with that of control livers. Furthermore, the capacity of liver homogenates to synthesize ascorbic acid from glucuronic acid was greatly reduced in infected mice. Therefore it is unlikely that the increase in ascorbic acid content of parasitized red blood cells is a consequence of increased biosynthesis and release of ascorbic acid by the host liver. We have not been able to exclude the possibility that the malarial parasite itself may be capable of de novo synthesis of ascorbic acid.

Animals↗

PubMed1986

Protection of vitamin E from oxidation by increased ascorbic acid content within Plasmodium vinckei-infected erythrocytes.

Erythrocytes isolated from mice at a late stage of infection with the malarial parasite Plasmodium vinckei contained increased levels of vitamin E, but neither control nor infected erythrocytes contained detectable levels of alpha-tocopherolquinone, an oxidation product of vitamin E. Total levels of the antioxidant, vitamin C, were more than doubled in the same populations of highly parasitized erythrocytes. These observations, and the lower ratio of oxidized to reduced forms of ascorbic acid in parasitized compared to nonparasitized erythrocytes, raise the possibility that increased redox-cycling between the two vitamins may account for the failure to detect alpha-tocopherolquinone. Thus, late in infection of mice with the lethal parasite P. vinckei, the content and redox state of erythrocytic ascorbic acid is altered so that it protects vitamin E, and presumably the parasitized red cell and its contents, from oxidative damage.

Animals↗

PubMed1986

Antioxidants in plasma from mice infected with Plasmodium vinckei.

The late stage of infection of mice with the malarial parasite Plasmodium vinckei was accompanied by significant changes in the content of most antioxidants within plasma. The plasma concentrations of uric acid and vitamin C increased, in contrast to those of vitamin E and total plasma proteins, whilst the activity of superoxide dismutase did not change significantly. In contrast to the situation within erythrocytes, the ratio of partly oxidized forms of vitamin C (dehydroascorbate and diketogulonic acid) to reduced ascorbic acid failed to decrease as a result of malarial infection. These results are consistent with earlier findings and add to the idea that malarial infection may result in oxidative tissue damage.

Animals↗

PubMed1985

Oxidative stress and protective mechanisms in erythrocytes in relation to Plasmodium vinckei load.

The protection of mouse erythrocytes (RBC) parasitized with Plasmodium vinckei vinckei against activated oxygen species was examined in relation to the intraerythrocytic parasite load. RBC from highly infected animals were separated by density gradient centrifugation into six bands with increasing parasite content and with parasitemias ranging from 17% to 100%. Increase in parasite load was accompanied by a decrease in the activities of the enzymes superoxide dismutase (EC 1.15.1.1), catalase (EC 1.11.1.6), glutathione peroxidase (EC 1.11.1.9), glutathione reductase [NAD(P)H] (EC 1.6.4.2), and NADH-methemoglobin reductase (EC 1.6.2.2; NADH:ferricytochrome b5 oxidoreductase) in the RBC lysates. In contrast, the total amount of reduced glutathione increased in the highly parasitized bands. Furthermore, the vitamin E content of all RBC bands, including the one that contained mainly nonparasitized erythrocytes, was 3- to 5-fold higher than that of control noninfected RBC. Increasing parasite load was accompanied by an increase in the production of malonyldialdehyde, indicating enhanced lipid peroxidation. Our results indicate that oxidative stress is experienced by all RBC during a malarial infection and is accompanied by a variety of changes in the antioxidant defense mechanisms of the host and the parasite. Furthermore, it appears that the plasma membrane of the host cell is better protected against oxidative injury than are the membranes surrounding the parasite.

Animals↗

PubMed1984

Oxygen uptake associated with Sendai-virus-stimulated chemiluminescence in rat thymocytes contains a significant non-mitochondrial component.

Sendai virus (150 haemagglutinating units/10(6) cells) stimulates rat thymocytes incubated in medium containing 5 mM-glucose at 37 degrees C to produce luminol-dependent chemiluminescence and a simultaneous increase in O2 consumption of 40%. Stimulation of thymocytes with Sendai virus is accompanied by reduction of exogenous acetylated ferricytochrome c, which is inhibited by superoxide dismutase, and the quantitative conversion of ferricyanide to ferrocyanide, which is not. Replacement of air in the gas space with N2 inhibits the chemiluminescent response by 97% but does not prevent the virus-stimulated reduction of ferricyanide. The non-permeant ferricyanide anion (2 mM) also inhibits the chemiluminescent response to Sendai virus, its accompanying 'extra' O2 uptake and the reduction of acetylated ferricytochrome c without affecting the basal respiration of the cells. Thymocytes in which the basal O2 consumption has been stimulated maximally with dinitrophenol (10 microM) or inhibited completely with antimycin A (0.1 microM) respond to Sendai virus with an additional increment of ferricyanide-inhibitable O2 consumption. The chemiluminescent response to virus is not inhibited by concentrations of antimycin A that block the basal respiration completely. We suggest that a portion of the increased O2 uptake induced by Sendai virus is involved in the non-mitochondrial reduction of O2 to O2- at the cell surface where the non-permeant ferricyanide anion inhibits O2-. formation by acting as an alternative high-affinity electron acceptor to O2.

Animals↗

PubMed1984

Production of luminol-reactive oxygen radicals during Plasmodium vinckei infection.

We tested the ability of whole blood and enriched fractions of peripheral blood polymorphonuclear leukocytes obtained from mice during the course of infection with Plasmodium vinckei to produce luminol-mediated chemiluminescence in response to phagocytic and nonphagocytic stimuli. The chemiluminescence response of whole blood to all stimuli increased dramatically and nonlinearly as the infection progressed, and there was a concomitant increase (80%) and decrease (70%) in the total numbers of leukocytes and erythrocytes, respectively. The proportion of polymorphonuclear leukocytes in the total leukocyte population increased threefold. On a per cell basis and at a constant hematocrit, the chemiluminescence response of peripheral leukocytes from infected animals to phorbol myristate acetate or opsonized zymosan was only slightly greater than that of cells from uninfected animals. Polymorphonuclear leukocytes isolated from the blood of infected animals also showed no large increase per cell in chemiluminescence responsiveness. Thus, although leukocyte numbers increase during a murine malarial infection, there appears to be no major change in the capacity of individual peripheral blood leukocytes to produce activated species of oxygen. However, the physiological reduction in the total concentration of hemoglobin at high parasitemia, due to hemolysis and hemoglobin digestion by the parasites, increases the possibility of oxygen radical-mediated damage to tissues and intraerythrocytic parasites as a result of decreased antioxidant protection.

Animals↗

PubMed1982