Mechanism of action of 5‐arninosalicylic acid

Механизм действия 5-аминосалициловой кислоты
Neville A Punchard, Simon Greenfield, R. P. H. Thompson
1992-01-01

5-Aminosalicylic acidArachidonic acid metabolismInflammatory bowel diseaseReactive oxygen species scavengingSulphasalazine
5-Aminosalicylic Acid (5-ASA) has been used for over 50 years in the treatment of inflammatory bowel disease in the pro-drug form sulphasalazine (SASP). SASP is also used to treat rheumatoid arthritis. However whether the therapeutic properties of SASP are due to the intact molecule, the 5-ASA or sulphapyridine components is unknown. Several mechanisms of action have been proposed for 5-ASA and SASP including interference in the metabolism of arachidonic acid to prostaglandins and leukotrienes, scavenging,of reactive oxygen species, effects on leucocyte function and production of cytokines. However, it is unlikely that the anti-inflammatory properties of SASP and 5-ASA are due to several different properties but more likely that a single property of 5-ASA explains the theraapeutic effects of 5-ASA and SASP. Reactive oxygen species (ROS) are involved in the metabolism of prostaglandins and leukotrienes and can act as second messengers, and so the scavenging of ROS may be the single mechanism of action of 5-ASA that gives rise to its antiinflammatory effects in both inflammatory bowel disease and rheumatoid arthritis.
1
Reactive oxygen species scavenging is proposed as the unifying mechanism because reactive oxygen species participate in prostaglandin and leukotriene metabolism and function as second messengers.
2
Several mechanisms have been proposed for 5-aminosalicylic acid, including modulation of arachidonic-acid metabolism, reactive-oxygen-species scavenging, leukocyte effects, and cytokine regulation.
3
Sulphasalazine’s therapeutic effects may arise from 5-aminosalicylic acid rather than the intact molecule or sulphapyridine component.
4
The abstract argues that a single mechanism is more likely than multiple independent properties to explain the anti-inflammatory actions of 5-aminosalicylic acid and sulphasalazine.
5
This proposed mechanism could explain the therapeutic effects of 5-aminosalicylic acid and sulphasalazine in both inflammatory bowel disease and rheumatoid arthritis.

5-aminosalicylic acid (5-ASA) and sulphasalazine (SASP) in inflammatory diseases

The anti-inflammatory mechanism of action, particularly reactive oxygen species scavenging and its effects on eicosanoid metabolism and inflammatory signaling

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1992-01-01
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Neville A Punchard
Simon Greenfield
R. P. H. Thompson
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