5-Aminosalicylic Acid, a Co-Factor for Colonic Prostacyclin Synthesis?

Hoult, J.R.S.; Page, H.

doi:10.1016/s0140-6736(81)90502-x

Cited by 45 publications

(5 citation statements)

References 13 publications

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“…It is possible that 5‐aminosalicylic acid mediates its effect on platelet activation at least in part by inhibition of cyclo‐oxygenase and alteration in the profile of eicosanoids including thromboxane A 2 , produced by platelets and the colonic mucosa 59 , . 60 The effects of 5‐aminosalicylic acid on eicosanoid production are, however, controversial, with evidence of 5‐aminosalicylic acid both inhibiting and enhancing eicosanoid production in the colon 59 –61 . Although thromboxane A 2 induces platelet activation, thrombin‐stimulated platelet activation is not entirely dependent on thromboxane A 2 expression 62 , .…”

Section: Discussionmentioning

confidence: 99%

Inhibition of platelet activation by 5‐aminosalicylic acid in inflammatory bowel disease

Carty

Macey

Rampton

2000

Aliment Pharmacol Ther

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Background: Platelets play an important role in inflammation and are activated in inflammatory bowel disease. Micro‐vascular thrombosis in the gut wall leading to intestinal micro‐infarction may be a pathogenic feature of Crohn’s disease. 5‐Aminosalicylic acid is an effective treatment for patients with inflammatory bowel disease. Aims: To assess the effects of 5‐aminosalicylic acid on platelet activation, when taken orally and in vitro by patients with inflammatory bowel disease. Methods: Spontaneous and thrombin‐induced platelet activation were studied using fluorescent antibodies to the activated platelet surface glycoprotein P‐selectin and flow cytometry. Results: Baseline platelet activation in inflammatory bowel disease was significantly greater than that in controls (P=0.0003). Independent of diagnosis or disease activity, spontaneous ex‐vivo platelet activation was 50% lower in patients with inflammatory bowel disease taking 5‐aminosalicylic acid orally than in those not on such treatment (P < 0.05). In vitro, 5‐aminosalicylic acid significantly reduced both spontaneous (P < 0.03 for ≥1 μM 5‐aminosalicylic acid) and thrombin‐induced platelet activation (P < 0.02 for ≥ 1 μM 5‐aminosalicylic acid). Conclusions: 5‐Aminosalicylic acid given either orally or in vitro inhibits platelet activation. If this effect reflects an in vivo action in the gut, it could contribute to the beneficial actions of 5‐aminosalicylic acid in inflammatory bowel disease.

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Section: Discussionmentioning

confidence: 99%

Inhibition of platelet activation by 5‐aminosalicylic acid in inflammatory bowel disease

Carty

Macey

Rampton

2000

Aliment Pharmacol Ther

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“…7 The interpretation of the conflicting data concerning prostaglandins and their possible role in ulcerative colitis has been further complicated by the recent observation of increased in vitro leukotriene formation in the inflamed rectal mucosa.12 Not only the lack of reliable data on colonic concentrations of sulphasalazine and its metabolites, but also the methodological problems concerning determination of prostaglandins in biological material and the choice of an experimental design, which prevents non-specific stimulation of prostaglandin biosynthesis, provide fundamental difficulties to establish the pathophysiological role of prostaglandins.13…”

mentioning

confidence: 99%

Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls.

Lauritsen¹,

Hansen²,

Bytzer³

et al. 1984

Gut

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SUMMARYThe role of arachidonic acid metabolites and the mode of action of 5-aminosalicylic acid, the active moiety of sulphasalazine and disodium azodisalicylate, in ulcerative colitis remain obscure. Therefore, experiments were performed in which the effects of medication on immunoreactive prostaglandin (PG) E2 concentrations in free faecal water were assessed using the equilibrium in vivo dialysis of faeces. Colonic PGE2 concentrations in patients with active ulcerative colitis (n= 11) ranged from 2035-18 000 pg/ml to be compared with a range of 103-188 pg/ml in healthy volunteers (n=10; p<0.001). In all healthy volunteers PGE2 concentrations decreased slightly (p<005) after disodium azodisalicylate intake 2 g/day, whereas low dose disodium azodisalicylate (0.25 g/day) caused no change. In patients with ulcerative colitis in complete clinical, sigmoidoscopic, and histologic remission withdrawal of sulphasalazine (2 g/day; n=6) increased PGE2 concentrations to values above normal levels (p<005) which returned to pretrial values (p<005) on disodium azodisalicylate (2 g/day; n=7). In conclusion, increased PGE2 in free faecal water indicates an abnormality in the colonic mucosa, even in the absence of conventional signs of inflammation. We could not confirm the hypothesis that sulphasalazine and 5-aminosalicylic acid exert their therapeutic effect through promotion of endogenous cytoprotective prostaglandins. In contrast, the observation that raised PGE2 concentrations were normalised by disodium azodisalicylate in patients with inactive ulcerative colitis suggests that subclinical disease activity was decreased by 5-aminosalicylic acid.Both cyclooxygenase and lipoxygenase products of arachidonic acid metabolism have been implicated in the pathogenesis of ulcerative colitis. The findings of increased amounts of prostanoids in faeces and rectal mucosa of patients with ulcerative colitisl-3 provided the hypothesis that prostaglandins may mediate the inflammatory response. The therapeutic effect of 5-aminosalicylic acid which is proved to be the major, though not necessarily the only active component of sulphasalazine,4 may be related to the anti-inflammatory activity of the substance which is a salicylate and a weak prostaglandin

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“…However, 5-ASA which has also been shown to be effective in treating ulcerative colitis (Azad Kahn, Piris & Truelove, 1977) did not affect [3H]-PGE1 metabolism in vitro in doses up to 2.6 mM. Recently, Hoult & Page (1981) showed that 5-ASA enhanced 6-keto PGF1I, synthesis in human colonic mucosal biopsies when a dose of 500 pM was used but synthesis was inhibited by 5000 pM. This contrasts with the results of Ligumsky et al (1981) and Sharon et al (1978) who showed that 5-ASA inhibited prostaglandin synthesis including 6-keto PGF1, by human biopsy specimens with doses of 326-1307 pM.…”

Section: Discussionmentioning

confidence: 99%

ULCERATIVE COLITIS: EFFECT OF SULPHASALAZINE, ITS METABOLITES AND INDOMETHACIN ON THE ABILITY OF HUMAN COLONIC MUCOSA TO METABOLIZE PROSTAGLANDINS in vitro

Hillier

Mason

Pacheco

et al. 1982

British J Pharmacology

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5-Aminosalicylic Acid, a Co-Factor for Colonic Prostacyclin Synthesis?

Cited by 45 publications

References 13 publications

Inhibition of platelet activation by 5‐aminosalicylic acid in inflammatory bowel disease

Inhibition of platelet activation by 5‐aminosalicylic acid in inflammatory bowel disease

Effects of sulphasalazine and disodium azodisalicylate on colonic PGE2 concentrations determined by equilibrium in vivo dialysis of faeces in patients with ulcerative colitis and healthy controls.

ULCERATIVE COLITIS: EFFECT OF SULPHASALAZINE, ITS METABOLITES AND INDOMETHACIN ON THE ABILITY OF HUMAN COLONIC MUCOSA TO METABOLIZE PROSTAGLANDINS in vitro

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