Effects of sulphasalazine on stress ulceration and mast cell degranulation in rat stomach

Ogle, C. W.; Cho, Chi H.

doi:10.1016/0014-2999(85)90512-6

Cited by 19 publications

(20 citation statements)

References 4 publications

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“…A tricyclic antidepressant drug, Amitriptyline has antiulcer effects in various ulcer models by different ways; for example it shows its antiulcer effect by inhibiting lipooxygenase enzyme in indomethacininduced ulcers and by an anti-leukotriene effect both peripheral and central areas in cold-stress induced ulcers [28]. In many experimental studies, antidepressant drugs have been shown to produce anti-ulcer effects by reducing histamine secretion from mast cells, inhibiting gastric acid secretion, and blocking leukotriene (LTC4, D4, E4) receptors [28]. To support this opinion, COX-2 is responsible for indomethacin's anti-inflammatory effects and COX-1 is responsible for indomethacin's GIS-adverse effects [9].…”

Section: Discussionmentioning

confidence: 99%

Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

Albayrak¹,

Hakan²,

Süleyman³

2015

EAJM

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Objective: Even though there are many drugs for the treatment of gastric ulcers, these drugs sometimes cannot succeed. Since the 1950s, antidepressant drugs have been used for several non-psychiatric indications. Many antidepressant drugs have been shown experimentally to produce antiulcer activity in various ulcer models. Moclobemide is an antidepressant drug which inhibits monoamine oxidase-A (MAO) enzyme selectively. When it is compared to the classic antidepressants drugs, moclobemide is the first choice in depression treatment because of its effectiveness and less side effects. This study aimed to investigate the antiulcer effects of moclobemide and to determine its relationship with antioxidant mechanisms in rat gastric tissue. Materials and Methods:The antiulcer activities of 10, 20, 40, 80, 150 mg/kg moclobemide and 20 mg/kg famotidine have been investigated on indomethacin-induced ulcers in rats, and the results have been compared with that of the control group. Results:Moclobemide decreased the indomethacin-induced ulcers significantly at all doses used. While used doses of moclobemide increased the glutathione (GSH), nitric oxide (NO) level and superoxide dismutase (SOD) activity, it decreased the malondialdehyde (MDA) level and myeloperoxidase (MPO) activity in stomach tissue when compared to the control group. Conclusion:It is determined that an antidepressant drug, moclobemide is a potent anti-ulcer agent. Inhibition of toxic oxidant radicals and activation of antioxidant mechanisms play a role in its antiulcer effect mechanisms.

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Section: Discussionmentioning

confidence: 99%

Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

Albayrak¹,

Hakan²,

Süleyman³

2015

EAJM

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“…It is also likely that protection by sulphasala zine against stress-induced ulceration results from inhibition of 5-lipoxvgenase activity [3] by its constituent 5-ASA [4,5]. Addition ally, sulphasalazine is a potent competitive inhibitor of leukotriene C4 (LTC4) synthe tase in basophilic leukaemia cells and of liver glutathione-S-transferase in rats [5], The potential to inhibit these enzymes [3][4][5][6], deduced from in vitro biochemical models, led to the suggestion in 1985 that LTC4 might be involved in the pathogenesis of stress-induced gastric lesions [2,3], This study attempts to gain an insight into the gastric anti-ulcer mechanism of ac tion of sulphasalazine, in relation to its two constituents, in stressed rats.…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Stress-Induced Gastric Ulcers by Sulphasalazine and Its Constituents (Sulphapyridine and 5-Aminosalicylic Acid) in Rats

Garg

Cho²,

Ogle³

1990

Pharmacology

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The effects of sulphasalazine and of its major constituents, sulphapyridine and 5-aminosalicylic acid (5-ASA), on gastric ulceration as well as on changes in mast cell counts and mucus levels in the glandular mucosa were examined in restrained rats exposed to 4°C (stress) for 2 h. Sulphasalazine (50, 100, 200 mg/kg), sulphapyridine (31.25, 62.5, 125 mg/kg) or 5-ASA (18.75, 37.5, 75 mg/kg) was injected subcutaneously 0.5 h before stress induction. Cold-restraint stress produced gastric glandular mucosal ulcers which were significantly reduced by all three doses of sulphasalazine and the higher doses of sulphapyridine and 5-ASA. Sulphasalazine prevented mast cell degranulation and increased the amount of mucus adhering to the mucosa. In contrast, the higher doses of sulphapyridine significantly increased only the mucus levels, whereas those of 5-ASA effectively prevented mast cell degranulation. The results show that the total effect of sulphasalazine is approximately equivalent to the summation of the actions of its component doses of sulphapyridine and 5-ASA. It is notable that sulphapyridine itself appears to be biologically active in reducing ulcer severity.

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“…In addition to the actions discussed above, SZP also inhibits mast cell degranulation (Ogle & Cho, 1985), the binding of f-MetLeuPhe to its receptor on neutrophils (Stenson et al, 1984) and various lipoxygenases including soybean lipoxygenase (Sircar et al, 1983) and neutrophil 5 and 12 lipoxygenases (Stenson & Lobos, 1982). All of these properties, if applicable in vivo, have potential beneficial effects in the prevention of gastric ulceration.…”

Section: Discussionmentioning

confidence: 99%

“…to produce their antiulcer effects in the dose ranges used suggests very strongly that it is the parent compound which is active and not products of splitting the diazo linkages by intestinal flora. Moreover, in the only other published study (to our knowledge) of the effects of SZP on gastric ulceration (stress-induced ulcers, Ogle & Cho, 1985), the compound was administered sub-cutaneously. In addition, the oral doses of SZP necessary to inhibit indomethacin-induced intestinal ulcers in the rat were at least 4 times greater than the active i.p.…”

Section: Discussionmentioning

confidence: 99%

“…Such an action would tend to increase the levels of tissue prostaglandins, leading to cytoprotection of the mucosa (as reviewed extensively by Miller, 1983). Moreover in the rat, SZP is active orally against indomethacin-induced intestinal ulcers in rats (Del Soldato et al, 1985), and prevents stress-induced gastric ulceration after sub-cutaneous injection (Ogle & Cho, 1985).…”

Section: Introductionmentioning

confidence: 99%

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Sulphasalazine and PhCL28A inhibit the formation of ethanol‐ and phenylbutazone‐induced rat gastric ulcers: lack of involvement of endogenous prostaglandins?

Berry¹,

Prouteau²,

Lloyd³

1988

British J Pharmacology

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1 The effects of sulphasalazine (SZP) and PhCL28A on macroscopic lesion formation and ex vivo prostaglandin inactivation were studied in the ethanol (ETOH) and phenylbutazone (PBT) models of gastric ulcers in the rat. Prostaglandin 'synthesis' during homogenisation of the stomachs was also studied in the latter model. 2 Both PhCL28A and SZP when injected i.p. prevented the formation of ETOH-and PBT-induced gastric ulcers with ED,5 values of 13 and 41 mg kg-' (vs ETOH) and 3 and 32 mg kg-' (vs PBT) for PhCL28A and SZP respectively. However, neither compound was active orally in the dose ranges used (up to 30 mg kg-' for PhCL28A and I00 mg kg-' for SZP). 3 Irrespective of the route of administration, SZP (100mgkg-') and PhCL28A (30mgkg-') produced slight but statistically significant decreases in ex vivo prostaglandin inactivation by 100,000 g cytosolic supernatants prepared from stomachs not receiving ulcerogen. When tested in vitro, PhCL28A (ICm, = 230 nM) was approximatively 480 times more potent than SZP (ICy, = 110 M) against rat stomach cytosolic prostaglandin inactivation.4 Both ETOH (50%, 5 ml kg-', orally) and PBT (200 mg kg-', orally) significantly decreased ex vivo gastric cytosolic prostaglandin inactivation. PhCL28A (30mg kg-', orally or i.p.) decreased prostaglandin inactivation still further after ulcerogen treatment except when given i.p. before ETOH treatment. SZP (100mg kg-') had a similar effect when given orally before PBT treatment. 5When the prostaglandin content of the stomach homogenates was used as a measure of ex vivo prostaglandin synthesis in the PBT experiments, PhCL28A 30 mg kg-' orally (but not i.p.) produced an 88% increase in prostaglandin E2 (PGE2) levels, but had no effect on 6-keto-PGF,, or thromboxane B2 formation during homogenization. SZP (100mg kg' i.p. or orally) was without effect. 6 We conclude from these results that the anti gastric ulcer activity of SZP and PhCL28A is independent of prostaglandin inactivation and endogenous prostaglandin formation is probably not involved.

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Effects of sulphasalazine on stress ulceration and mast cell degranulation in rat stomach

Cited by 19 publications

References 4 publications

Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

Investigation of Antiulcer and Antioxidant Activity of Moclobemide in Rats

Inhibition of Stress-Induced Gastric Ulcers by Sulphasalazine and Its Constituents (Sulphapyridine and 5-Aminosalicylic Acid) in Rats

Sulphasalazine and PhCL28A inhibit the formation of ethanol‐ and phenylbutazone‐induced rat gastric ulcers: lack of involvement of endogenous prostaglandins?

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