Effects Of Sulphasalazine Research Articles

Effects of Sulphasalazine in Cerebral Ischemia Reperfusion Injury in Rat

Management of cerebral ischemia/reperfusion (I/R) injury is still difficult process today. Aim of present study was to investigate therapeutic properties of sulfasalazine in cerebral transient I/R injury in rat. Except Control group (n=5), 20 Wistar albino rats were allocated for acute and chronic stage investigation of I/R injury, and temporary aneurysm clips were attempted to both internal carotid arteries for thirty min. Four hours later, 40mg/kg once a day sulfasalazine was administered to animals of SL-A and SL-C groups, orally. Animals were decapitated, following which pyknotic and necrotic neuronal cells, perivascular edema, irregularities of intercellular organization (IIO) of hippocampal regions, and cortical necrotic neurons of parietal lobe were counted or scaled histopathologically. Tissue malonyldialdehyde (MDA), myeloperoxidation (MPO), total nitrite/nitrate (NO), interleukin 1-beta (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) level values were evaluated biochemically. Sulfasalazine could reduce perivascular edema, IIO, cortical and hippocampal neuronal cell death in both stages. It could decrease MDA in acute stage, but not reduce IL-1β, IL-6, MPO, NO, and TNFα levels. It could increase IL-1β levels in chronic stage but not affect to IL-6, MPO, MDA, NO, TNF-α levels. Sulfasalazine could improve histopathological architecture of hypoxic tissue in both stages of I/R injury in rat. It could inhibit lipid peroxidation cascades just in acute stage. These results suggested that therapeutic mechanisms of sulfasalazine in cerebral I/R injury should be investigated by using more specific laboratory methods in future studies.

P090 Differential effects of sulphasalazine, azathioprine and prednisolone on the MAP-kinases gene expression in the TNBS-induced intestinal inflammation

elucidated but is currently presumed to result from a complex interplay among genetic, environmental, microbial and immune factors. Animal models of intestinal inflammation have given researchers a better understanding of the mechanisms involved in the pathogenesis of inflammatory bowel disease. Based on this, the aim of this study was to investigate the profile of NFkB, heparanase, HSP70 and HPRT gene expression in intestinal inflammation induced by TNBS (trinitrobenzenesulphonic acid) and to evaluate the effects of sulphasalazine, prednisolone and azathioprine on these gene expressions. Methods: Intestinal inflammation was induced in rat by intracolonic instillation of TNBS. Rats orally received 50mg/kg of sulphasalazine, 2mg/kg of prednisolone or 2mg/kg of azathioprine at 96, 72, 48, 24 and 2 hours before colitis induction. Animals were killed 48 h after colitis induction, colonic segments were obtained after laparotomy for macroscopic (colon weight and length and macroscopic damage score) and biochemical evaluation of myeloperoxidase (MPO) and alkaline phosphatase (AP) activities and glutathione (GSH) level. Gene expression analysis of NF-kB, heparanase, HSP70 and HPRT were performed on 100mg of colon tissue using qRT-PCR. Results: All gene expressions were increased in colitic animals when compared to healthy animals, indicating the involvement of these genes in intestinal inflammatory process induced by TNBS. Treatment of healthy animals with sulphasalazine and prednisolone did not affect gene expression, but it was observed that azathioprine enhanced HSP70 gene expression in healthy animals. On the other hand, treatment of colitic animals with sulphasalazine restored heparanase, HPRT and NFkB gene expression, while azathioprine restored the heparanase and HPRT gene expression and prednisolone only restored gene expression of the HPRT and HSP70. Conclusions: Gene expression of NF-kB, heparanase, HSP70 and HPRT participate on the intestinal inflammatory process induced by TNBS in rats and lead to new molecular markers or therapeutic targets. Furthermore, sulphasalazine, prednisolone and azathioprine produced differential pharmacological effects on NF-kB, heparanase, HSP70 and HPRT gene expression. Financial support: FAPESP and CAPES.

P089 Differential effects of sulphasalazine, azathioprine and prednisolone on the NF-kB, heparanase, HSP70 and HPRT gene expression in the TNBS-induced intestinal inflammation

P089 Differential effects of sulphasalazine, azathioprine and prednisolone on the NF-kB, heparanase, HSP70 and HPRT gene expression in the TNBS-induced intestinal inflammation

The role of the gastric mucosal sulphydryls in the ulcer-protecting effects of sulphasalazine

The role of gastric mucosal sulfhydryls in gastric ulceration, produced by restraint at 4 degrees C (stress) for 2 h, and in the ulcer-protecting effects of sulphasalazine and its constituents (sulphapyridine and 5-aminosalicylic acid), have been studied in rats. Stress significantly raised the mucosal sulphydryl content, but sulphasalazine and sulphapyridine did not influence these changes; only 5-aminosalicylic acid decreased the mucosal sulphydryl concentration. These results indicate that depletion of mucosal sulfhydryls does not occur in stress-induced ulceration, in contrast to what has been shown in other experimental ulcer models. The antiulcer effects of sulphasalazine or of any of its constituents may, therefore, not involve the sulphydryl mechanism.

Sulphasalazine fails to prevent development of mucosal ulceration and 5-lipoxygenase activity in guinea-pigs with chronic inflammatory bowel disease induced by combined bacterial immunization and oral carrageenin.

A model of inflammatory bowel disease in guinea-pigs involving a 14 day initial treatment with formalin-killed Bacteroides vulgatus subcutaneously and oral carrageenin plus live B. vulgatus for 10 days was used to determine the effects of sulphasalazine 100 mg kg-1 day-1 b.i.d., p.o. given for 4, 7 and 10 days after cessation of the bacterial/carrageenin treatment on the morphological and histological states of the established disease and on the production of the principal 5-lipoxygenase products, 5-hydroxyeicosatetraenoic acid and leukotriene B4. The drug treatment did not cause any significant changes in this established disease as measured by these parameters.

Efficacy of SLZ and MTX (alone or combination) on the treatment of active sacroiliitis in early AS

Sacroiliitis is an important sign of spondylarthritis (SpA) of which the prototype disease is ankylosing spondylitis. The radiographic changes required for diagnosing AS occur as late as 8-11 years after the onset of clinical symptoms. Nonsteroid anti-inflammatory drugs (NSAIDs) have been the main treatment for spondylitis of AS. For patients refractory or intolerant to NSAIDs, disease-modifying antirheumatic drugs (DMARDs) have been used as a second-line approach. Sulphasalazine (SLZ) is known as the best DMARD in treatment of peripheral arthritis; also methotrexate (MTX) is currently one of the most widely used DMARDs. But there was no objective information about inflammation of sacroiliac joints during treatment with these DMARDS that are the first places of the beginning point of SpA. For this purpose, in this study, the effect of SLZ and MTX, which are used alone and combination in 6 months, on treatment of active sacroiliitis, which is shown by dynamic magnetic resonance and acute phase reactants in laboratory has been investigated. 55 patients (F:M = 34:21) with active sacroiliitis [mean age = 37.05 + 13.03 year (n = 55)] were evaluated and determined by dynamic magnetic resonance imaging in this study. The better response in the SLZ treatment group than the other two groups has been obtained. Nevertheless, those changes were not statistically found different. In conclusion, the ratio of treatment of active sacroiliitis, especially early period, with SLZ as a DMARD is better than MTX or MTX + SLZ, but this difference is not statistically significant. A prospective study of the treatment of active sacroiliitis by DMARDs may be more illustrative.

Improved glycaemic control with disease remission in rheumatoid arthritis and hypoglycaemic effect of sulphasalazine

Improved glycaemic control with disease remission in rheumatoid arthritis and hypoglycaemic effect of sulphasalazine

Effect of sulphasalazine and balsalazide on histamine release from mast cells

Effect of sulphasalazine and balsalazide on histamine release from mast cells

The effects of sulphasalazine on urinary excretion of the hydroxypyridinium crosslinks of collagen in patients with rheumatoid arthritis.

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 +/- 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 +/- 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 +/- 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 +/- 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 +/- 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 +/- 3.16 nmol/mmol cr) than in the inactive (8.25 +/- 4.23 nmol/mmol cr) period in patients with premenopausal RA (p < 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 +/- 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 +/- 2.13 nmol/mmol cr) and inactive periods (5.08 +/- 0.87 nmol/mmol cr) (p > 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p < 0.01, r=0.5953 p < 0.01, r=0.6125 p < 0.01 and r=0.6232, p < 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.

The effect of sulphasalazine and mesalazine on renal function: A 7 year longitudinal study

The effect of sulphasalazine and mesalazine on renal function: A 7 year longitudinal study

The effects of sulphasalazine on male fertility

The effects of sulphasalazine on male fertility

Sulphasalazine: Mechanism of Action in Rheumatoid Arthritis

Sulphasalazine a drug used for the treatment of rheumatoid arthritis (RA) shows a wide range of biological activities all of which might contribute to the beneficial clinical effect seen during treatment of RA. This review summarizes some of the biological activities and discusses these in context of possible modes of action of the drug. Sulphasalazine has been described as an antibacterial drug, an anti-inflammatory drug or as an immunomodulator. From the reviewed data it is concluded that the effects of sulphasalazine on various immunological processes, are of outstanding importance for its mode of action.

Sulphasalazine desensitisation in patients with arthritis.

Skin rash is a common side effect of sulphasalazine. Desensitisation, with a gradual introduction of the drug, may prevent rash. This study reports a 33% (3/9 patients) success rate of desensitisation in patients with arthritis. Desensitisation should only be attempted if sulphasalazine has been efficacious in treating the joint symptoms.

Co-carcinogenic effect of sulphasalazine

Co-carcinogenic effect of sulphasalazine

Actions of sulphasalazine and analogues in animal models of experimental colitis

Experimental animal models proposed for the study of inflammatory bowel diseases have been numerous. The ability to modify the induced inflammation with pharmaceutical treatment, established for human disease, has not always been achieved. Sulphasalazine is mainly used for the medical management of ulcerative colitis and to a lesser extent for active colonie Crohn’s disease. The effects of sulphasalazine and the analogues olsalazine, 5-aminosalicylic acid and 4-aminosalicylic acid, in different experimental animal models and in particular the hapten-, immune complex- and dextran-models are reviewed.

Effects of sulphasalazine on lymphocyte functions

Sulphasalazine (SASP) is established as a second-line drug in the treatment of rheumatoid arthritis (RA) and some of the seronegative spondarthritides. It is not clear whether the parent compound, one of its two main metabolites or a combination is responsible for its therapeutic effect. Much of the drug’s action is also unknown. Since RA and the seronegative spondarthropathies ail share substantial immunopathology, the immune effects of SASP and/or its main metabolites may play a major part in its action.

Effects of sulphasalazine in experimental arthritis

The effects of sulphasalazine and related drugs on various models of arthritis are reviewed. Dosage regimen and duration of the treatment are of importance, as is the animal species, in determining clinical, biological, or radiological responses. Considering these parameters together with differences in administration protocols, it is not surprising that various drug effects are reported in the published studies. There is some evidence that sulphasalazine displays beneficial activity in attenuating experimental synovitis, but its influence only becomes apparent after a few weeks of therapy, thus functioning as a slow-acting antirheumatic drug. In contrast, sulphasalazine does not seem to be effective on the cicatricial ossifying process. Nevertheless, the respective therapeutic and remission-inducing effects of the parent drug, sulphasalazine, and its main moieties, 5-aminosalicylic acid and sulphapyridine, remain controversial.

Comparison of the effect of oral sulphasalazine, sulphapyridine and 5‐ amino‐salicylic acid on the in vivo antibody response to oral and systemic antigen.

1. Mice, whose drinking water contained sulphasalazine, sulphapyridine or 5-amino-salicylic acid, received an antigenic challenge by cholera toxin administered either orally or systemically. 2. Sulphasalazine treated mice made less specific antibody of IgA class provided the antigen also was administered orally (P = 0.009 for days 7-28). When the antigen was administered systemically, there was a vigorous anti-cholera toxin antibody response of IgG class, and a lesser IgM but only a weak IgA response. The effect of sulphasalazine in this case was confined to the IgG response, which was significantly suppressed on day 28 (P = 0.008). 3. Sulphapyridine and 5-amino salicylic acid had no significant effect on the anti-cholera toxin (CT) responses of all three classes. 4. It therefore appears that in this model, only sulphasalazine is capable of influencing the humoral immune system, the antibody class affected depending on the route of entry of antigen. This may have implications for conditions such as rheumatoid arthritis and chronic inflammatory bowel disease, for which sulphasalazine has been found useful.

The effect of sulphasalazine and its metabolites on histamine release from human colonic and gastric mast cells

Mast cells isolated from human colon and stomach released histamine on challenge with anti-human IgE. Sulphasalazine (1 nM−100 μM) had no effect on the secretion induced by optimal concentration of anti-IgE but potentiated the release evoked by sub-maximal amounts of the ligand. Over the same concentration range, sulphapyridine had no effect on the release. However, 5-aminosalicylic acid (5-ASA) produced a dose-dependent inhibition of secretion with an IC50 ofca 50 μM. These results are discussed in terms of the possible therapeutic action of sulphasalazine.

Inhibition of leucocyte adhesion molecule upregulation by tumor necrosis factor alpha: a novel mechanism of action of sulphasalazine.

The effects of the cytokine tumour necrosis factor alpha and the calcium ionophore A23187 upon CD11a, CD11b, CD11c and CD18 leucocyte membrane expression was analysed in whole blood using monoclonal antibodies and flow cytometry. Both agents significantly increased the density of CD11b/CD18 membrane expression on monocytes and granulocytes, but had no effects on adhesion molecule expression on lymphocytes. The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA) and sulphapyridine upon adhesion molecule upregulation were then examined; 10(-3) and 10(-4) M sulphasalazine and 5-ASA significantly reduced tumour necrosis factor alpha induced CD11b/CD18 upregulation on monocytes and granulocytes but had no effects upon A23187 mediated upregulation. Sulphapyridine was inactive. These results suggest that sulphasalazine and 5-ASA may interfere with mechanisms of leucocyte recruitment in inflammatory bowel disease.