Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two phases of adjuvant arthritis, acute phase (4 days after adjuvant inoculation) and chronic phase (21 and 29 days after adjuvant inoculation) were studied in male rats. The effect of administration of vitamin E in a daily oral dose of 147 mg/kg body wt. for one week against these phases of arthritis were demonstrated before and after adjuvant inoculation. Results showed that administration of the vitamin before and after adjuvant inoculation increased the lowered serum-SH group in arthritic rats so that their level was restored to pre-arthritic values especially in chronic treated group. Meanwhile, these treatments produced no change in the increased level of blood GSH or erythrocyte SOD activity of arthritic rats. The results showed also that administration of vitamin E before adjuvant inoculation increased significantly the level of alpha 2-M while it did not alter the increased serum Cp in acute phase. However, administration of the vitamin after adjuvant inoculation failed to exert any change in these parameters. In the meantime, these treatments tended to increase the lowered A/G of arthritic rats in different phases especially in acute one. These observations suggest that antioxidants such as vitamin E may be beneficial for arthritis.
 ...
PMID:Biochemical changes in arthritic rats under the influence of vitamin E. 138 81

In this paper we studied the modulating inflammatory activity of iron in the adjuvant arthritis, taking indomethacin as a standard antiinflammatory drug and a superoxide dismutase derivative (MPEG-SOD) as a scavenger of free radicals. Moreover, we evaluated the changes in potential intestinal pathogens requiring iron for growth, in order to study the role of bacteria in the altered gastrointestinal functions observed during arthritis. We observed a 50% arthritis inhibition on the 14th day with MPEG-SOD plus desferrioxamine, a significant decrease in serum iron in arthritic rats compared to controls, and a significant Cl. perfringens increase on the 28th day in the presence of MPEG-SOD. Our data demonstrate that hypoferremia, in arthritis, is a protective mechanism overall in the early phase and could protect the intestinal tract by inhibiting the development of potential pathogens.
 ...
PMID:Desferrioxamine potentiated SOD antiinflammatory activity in rat adjuvant arthritis: role of iron and bacterial toxins. 144 28

Peritoneal and peripheral blood monocyte-macrophages from inbred Lewis (LEW) rats generate higher levels of reactive oxygen intermediates (ROI) in response to group A streptococcal cell walls (SCW) than do similar populations of cells from histocompatible Fischer rats. This differential sensitivity of the phagocytes to SCW is reflected in differences in susceptibility of the two strains to the development of arthritis in response to SCW. After systemic administration of the SCW, LEW rats develop acute and chronic erosive polyarthritis, whereas the Fischer rats are arthritis resistant. Inasmuch as these data suggested that the SCW-induced release of inflammatory cell products such as ROI might be an important contributory factor in the pathogenesis of arthritis in the LEW rats, the animals were injected with SCW and treated with ROI inhibitors. A single intraarticular injection of superoxide dismutase or catalase significantly reduced the SCW-induced inflammatory response and evolution of erosive arthritis in the treated animals (articular index 3.6 +/- 0.36 for SCW only vs 1.4 +/- 0.3 for SCW + SOD; p less than 0.001; n = 6). These data indicate that ROI play a pivotal role in synovitis and, furthermore, that suppression of these inflammatory mediators modulates both acute and chronic SCW-induced inflammation of the joint.
 ...
PMID:Inhibitors of reactive oxygen intermediates suppress bacterial cell wall-induced arthritis. 165 94

In previous studies we observed an enhanced anti-inflammatory activity of MPEG-SOD derivatives in acute inflammation in rat. To assess the activity in chronic inflammation we tested the compound with longer half-life (MPEG-SOD 18) in complete adjuvant arthritis in rat. According to the prophylactic schedule of treatment (i.m. administration at alternative days of 10 mg/kg from day 3 to day 21), the MPEG-SOD derivative reduced arthritic lesions in a significant way (P less than 0.01 at 14th, 21st, 28th day). Indomethacin, administered i.m. daily at the dose of 1.5 mg/kg according to the same schedule, significantly inhibited adjuvant arthritis each time it was considered (% of inhibition are 66.5% at 14th day, 58.3% at 21st day and 50.8% at 28th day). Native SOD and inactivated enzyme, administered from day 3 to day 21 did not show any anti-inflammatory properties. According to the therapeutic schedule of treatment (from day 14 to day 28), neither MPEG-SOD nor native SOD showed antiarthritic activity.
 ...
PMID:Anti-inflammatory activity of monomethoxypolyethylene glycol superoxide dismutase on adjuvant arthritis in rats. 204 60

Recombinant human interleukin-1 alpha (IL-1 alpha) induced a time-dependent (0-72 hours) and concentration-dependent (0.01-10 ng/ml) production of metalloproteinases (collagenase, gelatinase, stromelysin) and prostaglandin E2 (PGE2) in rabbit articular chondrocytes (RAC). Exposure of RAC to recombinant human platelet-derived growth factor homodimer BB (PDGF-BB; 2-200 ng/ml) in the presence of stimulatory and substimulatory concentrations of IL-1 alpha resulted in a marked augmentation of metalloproteinase and PGE2 production. PDGF-BB exerted no agonist effects on RAC responsiveness. PDGF-BB up-regulated the number of IL-1 receptors per chondrocyte but had no effect on receptor affinity. Cycloheximide and actinomycin D caused a concentration-dependent suppression of the PDGF-BB-mediated potentiation of radiolabeled IL-1 alpha binding to RAC and cell responsiveness to IL-1 alpha. Similarly, IL-1 increased the number of PDGF receptors on RAC without changing receptor affinity. These data are discussed within the context of cytokine-growth factor interactions as components of the pathogenesis of arthritic diseases.
Arthritis Rheum 1991 Jun
PMID:Platelet-derived growth factor potentiates cellular responses of articular chondrocytes to interleukin-1. 205 15

The effect of SOD on staphylococcal arthritis has not been successfully evaluated to date. We developed an animal model to investigate the correlation. Using 16 rabbits divided into four groups, we injected two groups with staphylococcus aureus and the other two with NaCl. One group in each was also injected with SOD. The presence of SOD activity in untreated and infected knee joints of rabbits over a period of 72 hours showed no significant difference. TBA-reactive substances (TBARS) measured in joint fluid and plasma did differ in each of the groups, with the highest values found in animals with septic arthritis treated with SOD. This finding corresponded especially with the histological investigation. Joints of infected animals intra-articularly injected with SOD also showed histologically significantly more inflammation, a higher amount of bacteria in the joint cavity, and more distinct joint damage than joints injected only with bacteria. The mechanisms responsible for this SOD effect remain to be determined.
 ...
PMID:Staphylococcal arthritis--effects of superoxide dismutase on infected knee joints of rabbits. 258 50

The metabolic disorder, alkaptonuria, is distinguished by elevated serum levels of 2,5-dihydroxyphenylacetic acid (homogentisic acid), pigmentation of cartilage and connective tissue and, ultimately, the development of inflammatory arthritis. Oxygen radical generation during homogentisic acid autoxidation was characterized in vitro to assess the likelihood that oxygen radicals act as molecular agents of alkaptonuric arthritis in vivo. For homogentisic acid autoxidized at physiological pH and above, yielding superoxide (O2-)2 and hydrogen peroxide (H2O2), the homogentisic acid autoxidation rate was oxygen dependent, proportional to homogentisic acid concentration, temperature dependent and pH dependent. Formation of the oxidized product, benzoquinoneacetic acid was inhibited by the reducing agents, NADH, reduced glutathione, and ascorbic acid and accelerated by SOD and manganese-pyrophosphate. Manganese stimulated autoxidation was suppressed by diethylenetriaminepentaacetic acid (DTPA). Homogentisic acid autoxidation stimulated a rapid cooxidation of ascorbic acid at pH 7.45. Hydrogen peroxide was among the products of cooxidation. The combination of homogentisic acid and Fe3+-EDTA stimulated hydroxyl radical (OH.) formation estimated by salicylate hydroxylation. Ferric iron was required for the reaction and Fe3+-EDTA was a better catalyst than either free Fe3+ or Fe3+-DTPA. SOD accelerated OH. production by homogentisic acid as did H2O2, and catalase reversed much of the stimulation by SOD. Catalase alone, and the hydroxyl radical scavengers, thiourea and sodium formate, suppressed salicylate hydroxylation. Homogentisic acid and Fe3+-EDTA also stimulated the degradation of hyaluronic acid, the chief viscous element of synovial fluid. Hyaluronic acid depolymerization was time dependent and proportional to the homogentisic acid concentration up to 100 microM. The level of degradation observed was comparable to that obtained with ascorbic acid at equivalent concentrations. The hydroxyl radical was an active intermediate in depolymerization. Thus, catalase and the hydroxyl radical scavengers, thiourea and dimethyl sulfoxide, almost completely suppressed the depolymerization reaction. The ability of homogentisic acid to generate O2-, H2O2 and OH. through autoxidation and the degradation of hyaluronic acid by homogentisic acid-mediated by OH. production suggests that oxygen radicals play a significant role in the etiology of alkaptonuric arthritis.
 ...
PMID:Homogentisic acid autoxidation and oxygen radical generation: implications for the etiology of alkaptonuric arthritis. 312 48

Comparison of the anti-inflammatory properties of superoxide dismutases from different sources using different models (carrageenan and adriamycin induced inflammation, adjuvant-induced arthritis) in rats shows a very wide range of activity from extremely good to zero. Neither circulating life time nor intracellular penetration are of importance. The mechanism of biological activity of the SODs is discussed in detail, and binding to an interphase situation on the outer cell surface is postulated. As a consequence of these various considerations it is predicted that clinical application of human Cu-SOD in humans may well be much less spectacular than is commonly assumed, and indeed may be somewhat disappointing.
 ...
PMID:Anti-inflammatory activity of superoxide dismutases: comparison of enzymes from different sources in different models in rats: mechanism of action. 333 56

Adjuvant arthritis was induced in rats by the injection of Mycobacterium tuberculosis, and its severity was scored according to the macroscopic findings of the legs, tail, and ears. The average score so obtained was lower in SOD-injected rats than in the control group. The depression of albumin/globulin ratio was inhibited significantly in rats treated with 10.0 mg/kg of SOD. The levels of acid phosphatase and beta-glucuronidase were elevated after the administration of an adjuvant, and these lysosomal enzymes showed a remarkable increase in the control rats, while the elevation was inhibited in rats injected with 10.0 mg/kg of SOD. The levels of TBA-reactive substances in the sera and synovia were elevated at 2 weeks after the injection of adjuvant and decreased thereafter. In rats injected with 5.0 mg/kg or 10.0 mg/kg of SOD, the increase in both serum and synovial levels of TBA reactants was inhibited significantly. These observations suggest that the aggravation of adjuvant arthritis may be associated with lipid peroxidation due to superoxide, and that SOD may be beneficial for the treatment of arthritis.
 ...
PMID:The increase of lipid peroxidation in rat adjuvant arthritis and its inhibition by superoxide dismutase. 401 32

The anti-arthritic and anti-inflammatory efficacy of CuPu(Py)2 ([N,N'-bis(2-pyridylmethylene)-1,4-butanediamine] (N,N',N",N"))-Cu(II), a serum-stable active center analogue of Cu2Zn2-superoxide dismutase (SOD; EC 1.15.1.1), was tested in male DBA/1 x B10A (4R) mice suffering from potassium-peroxochromate-induced (PIA) or collagen type II-induced arthritis (CIA). Parameters including the arthritis index, the plasma SOD activity, and the inhibition of phagocytic responses in unseparated blood were used for the assessment of disease activity. A dose-dependent suppression of arthritis was noted in both models. The ED50 was 2.5 +/- 0.4 mumol/kg/day of CuPu(Py)2 for PIA and 4.0 +/- 1.1 mumol/kg/day for CIA. The arthritis index correlated with both the levels of reactive oxygen species (ROS) generated by phorbol ester-activated neutrophils and monocytes in unseparated blood (r = 0.892) and the SOD-like activity in plasma (r = 0.857). CuPu(Py)2 inhibited also the lipoplysaccharide-induced release of tumor necrosis factor alpha from human monocytes and neutrophils in a dose-dependent manner. Unlike SOD, which exerts successful anti-rheumatic activity mainly upon intra-articular injection, the SOD-mimic CuPu(Py)2 can be applied systemically. Non-proteinaceous low molecular weight antioxidases may well be suited to control oxidative stress-derived damage in rheumatic diseases by modulation of ROS-dependent signal transduction pathways.
 ...
PMID:Suppression of arthritis by an active center analogue of Cu2Zn2-superoxide dismutase. 783 72


1 2 3 4 5 6 7 Next >>