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T Sahinoglu

Publications and source records attributed to T Sahinoglu.

12 recordsLinked to original sources
PubMed1996

The Role of Reactive Oxygen Species in Inflammatory Disease: Evaluation of Methodology

The production of reactive oxidants has been implicated in the pathology of a number of inflammatory conditions, including inflamed arthritic joints. Many assays for the detection of these oxidants in diseased states have been described, but there are a number of potential pitfalls in both experimental design and the interpretation of results obtained with these techniques. Here, we describe a number of commonly used assays to detect the production of reactive oxidants and critically discuss their usefulness and limitations. We focus on the role of xanthine oxidase in reactive oxidant production in inflammatory disease.

Journal Article↗
PubMed1995

Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen species by diseased human synovial tissue following ex vivo hypoxia-reoxygenation.

OBJECTIVE: To apply an electron spin resonance (ESR) spectroscopic technique as a means of determining the oxidising capacity of reactive oxygen species produced during hypoxia and reoxygenation of diseased human synovial tissue. METHODS: Twenty four specimens of fresh synovial tissue were obtained from patients undergoing primary total knee joint replacement and graded according to the degree of inflammation present. Tissue samples were subjected to an ex vivo hypoxia-reoxygenation cycle in the presence of the nitroso based spin trap, 3,5-dibromo-4-nitrosobenzene sulphonate. The degree of oxidation of the spin trap to a stable free radical was determined and followed with time. Control samples were subjected to hypoxia only. RESULTS: The results indicate that the oxidising capacity of reactive oxygen species produced by human synovial tissue varies with the degree of inflammation present. Only the more inflamed specimens, from both rheumatoid arthritis and osteoarthritis patients, demonstrated increased production of reactive oxygen species when subjected to a hypoxia-reoxygenation cycle. This change was reduced by both competitive and non-competitive inhibitors of the endothelial based enzyme xanthine oxidase. The relative concentration of reactive oxygen species generated by the synovial tissue samples correlated with the mean capillary density of the specimens. CONCLUSION: This study supports the hypothesis of movement induced hypoxicreperfusion injury of the chronically inflamed joint by demonstrating the generation of reactive oxygen species within inflamed human synovium following an ex vivo hypoxia-reoxygenation cycle. Evidence is presented that the microvascular endothelial based enzyme xanthine oxidase is the predominant source of ESR detectable oxidising species in inflamed synovial specimens exposed to hypoxia-reoxygenation.

Adult↗
PubMed1995

The joint, a redox sensitive microenvironment?--an hypothesis.

Antioxidant depletion in a normal adult increases the risk of developing rheumatoid arthritis (1). We discuss how redox processes "control" the inflammatory reaction and suggest that the synovium is a peculiarly "redox-sensitive" microenvironment. This discussion will be illustrated by a zonal model of tissue injury to represent the diseased synovium.

Animals↗
PubMed1992

The selective protection afforded by ebselen against lipid peroxidation in an ROS-dependent model of inflammation.

The effects of an experimental model of hydrogen-peroxide-induced foot pad oedema on indices of oxidative damage to biomolecules have been investigated. We have demonstrated increased levels of fluorescent protein and lipid peroxides occurring in plasma at 24 and 48 h post-injection. In addition, a decrease in the degree of galactosylation of IgG was observed which kinetically related the degree of inflammation and to the increase in protein autofluorescence (a specific index of oxidative damage). The effects of ebselen, a novel organoselenium compound which protects against oxidative tissue injury in a glutathione-peroxidase-like manner, have also been examined in this model. Pretreatment of animals with a dose of 50 mg/kg ebselen afforded significant and selective protection against lipid peroxidation only. This effect may contribute to the anti-inflammatory effect of this agent in hydroperoxide-linked tissue damage.

Animals↗
PubMed1992

Application of methionine as a detector molecule for the assessment of oxygen radical generation by human neutrophils and endothelial cells.

Diverse cell types can generate reactive oxygen species (ROS) which are implicated in many disease processes and are ascribed both beneficial and deleterious roles. In vitro studies of this phenomenon indicate that properties of the microenvironment in culture influence the cells' behaviour with regard to ROS generation in vivo. To date, however, the assessment of cellular ROS generation has been limited to techniques which are invasive of the culture environment, or require cells to be in suspension. This study describes the application of NMR spectroscopy to the detection of ROS generation, a technique which is non-invasive of the cell culturing environment.

Cell Division↗
PubMed1991

Influence of disodium aurothiomalate on the activities of xanthine dehydrogenase and xanthine oxidase in endothelial cells.

The effect of aurothiomalate in modulating the conversion of xanthine dehydrogenase to its superoxide producing oxidase form in rat and human liver cytosolic preparations has been investigated. Low concentrations (10(-8)-10(-5) mol.dm-3) of this second-line agent were found to inhibit the conversion of the dehydrogenase to its corresponding oxidase form. High concentrations (10(-4) mol.dm-3), however, accelerated this conversion. It is possible that the influence of aurothiomalate on the relative proportions of xanthine dehydrogenase and xanthine oxidase is a reflection of the gold(I) blockage of critical thiol(ate) or sulphido ligands present in this enzymatic system. These effects may form the basis of aurothiomalate's anti-proliferative action on endothelial cells.

Animals↗
PubMed1991

Localisation of xanthine oxidase to synovial endothelium.

The presence of the xanthine oxidase enzyme system has been demonstrated in the rheumatoid synovium. This supplies a reactive oxygen species generating system to synovium that is subjected to hypoxic-reperfusion cycles (cf inflamed rheumatoid synovium). An antibody to bovine milk xanthine oxidase has been used to localise the enzyme by immunohistochemistry to synovial endothelium. This implicates the endothelial cell as playing a major part in exacerbations of synovitis, induced by radicals.

Antigens↗
PubMed1990

Control of oxidative damage in rheumatoid arthritis by gold(I)-thiolate drugs.

The roles of anti-arthritic gold(I)-thiolate drugs such as disodium aurothiomalate ('Myocrisin') in the modulation or promotion of oxygen radical-mediated oxidative damage in vivo are reviewed. In particular, the precise molecular mechanisms by which these novel second-line agents exert their therapeutic effects are discussed in terms of (i) the direct and indirect control of enzymes involved in the generation or scavenging of reactive oxygen species (ROS) such as superoxide ion, hydrogen peroxide and hydroxyl radical, (ii) the protection of proteins and relevant enzyme systems against attack by ROS and (iii) their direct involvement in the production (at appropriate 'target' sites) or scavenging of ROS in vivo. In addition, the role of the orally-effective gold(I)-phosphine complex auranofin in the control of oxidative damage in rheumatoid arthritis is also discussed.

Antirheumatic Agents↗
PubMedDate not supplied

Role of the endothelial cell in osteoclast control: new perspectives.

The osteoclast is of central importance in the process of bone remodeling. Its function is regulated by hormones and locally produced factors. Endothelial cells occur in close proximity to the osteoclast. Some endothelial cell-derived products, including endothelins, nitric oxide, and reactive oxygen species, have been recently implicated as modulators of osteoclast function. Endothelins inhibit bone resorption and osteoclast margin ruffling (quiescence or Q effect) at concentrations similar to those effective for their primary vasoconstrictive action. Contrary to expectations, however, it has been shown that endothelin action on the osteoclast is not mediated through an elevation of cytosolic Ca2+. Nitric oxide (NO) produces marked cell retraction (retraction or R effect), but its detailed mode of action is unknown. However, it is clear that the effects of this autocoid are not due to enhanced cyclic guanosine monophosphate (cGMP) production, a transduction system commonly used by NO. Finally, the reactive oxygen species H2O2 has been shown recently to enhance osteoclastic activity. Thus, the reported effects of the endothelial cell-derived products on the osteoclast are generally consistent with a regulatory role for endothelial cells in osteoclast control and suggest the existence of unique activation pathways, well worth exploring further. Unravelling the responsible mechanisms may also help understand the pathophysiology of a range of bone and joint diseases. For example, in rheumatoid arthritis, there is increased H2O2 production from activated neutrophils, and bone resorption is a major pathophysiological feature.

Bone Remodeling↗