Enhanced gastric mucosal leukotriene B4 synthesis in patients taking non-steroidal anti-inflammatory drugs.

Abstract

The effects of longstanding non-steroidal antiinflammatory drug (NSAID) treatment on gastric mucosal synthesis of leukotriene B4 (LTB4), leukotriene C4 (LTC4), and prostaglandin E2 (PGE2) was studied. Gastric antral biopsies in 65 patients with arthritis taking NSAIDs and 23 control patients were taken and eicosanoid concentrations, stimulated by vortex mixing or calcium ionophore, were measured by radioimmunoassay. Median gastric mucosal synthesis of LTB4 was increased in patients taking NSAIDs compared with non-users: (0 9 (0 2-2 5) pg/mg v 0 (0-0.6) pg/mg (p<0001)). These differences persisted when subgroups of patients were analysed according to Helicobacter pylon colonisation or degree of mucosal injury. Synthesis of LTB4 was strongly associated with the presence of type C (chemical) gastritis. Increased synthesis of LTC4 was associated with Helicobacter pylori colonisation but not NSAID use. Synthesis of PGE2 was decreased in patients taking NSAIDs compared with control patients (p<0001). Enhanced gastric mucosal synthesis of LTB4 in patients taking NSAIDs may represent a primary effect of these drugs and could be implicated in the pathogenesis of gastritis and ulceration associated with NSAIDs.

Lipoxygenase inhibiting activity of some Malaysian plants

“…It has now been suggested that the therapeutic effects of agents inhibiting only COX-1 and COX-2 may be limited by preferential conversion of arachidonic acid to leukotrienes through the LOX pathway since leukotriene B 4 (LTB 4 ) is the main leukotriene that plays a major role in the inflammatory response (Hudson et al, 1993). Therefore, medications that inhibit both COX-1/2 and 5-LOX pathways are believed to be superior to conventional NSAIDs since they could produce a synergistic effect and achieve optimal anti-inflammatory activity by blocking the production of both leukotrienes and prostaglandins (Celotti & Laufer, 2001;Martel-Pelletier et al, 2003).…”

Anti-inflammatory and antinociceptive activities ofHomalium letestui

“…The LOX pathway produces leukotriene B4 (LTB4) that is the main leukotriene that plays a major role in the inflammatory response (Hudson et al, 1993). 5-LOX is the first and the key enzyme involved in the arachidonic acid pathway to produce leukotrienes (Zhang et al, 2002).…”

Anti-inflammatory potential of 2-styrylchromones regarding their interference with arachidonic acid metabolic pathways

“…Indeed, the PGE 2 , which has been mostly considered a pro-inflammatory mediator, has, on the other hand, given proves of involvement in antiinflammatory and pro-resolving responses [45][46][47]. Furthermore, the COX inhibition shunts the arachidonic acid metabolism toward the 5-LOX pathway enhancing the gastric mucosal damages due to the augmented production of LTB 4 [44,48] and inducing adverse reactions in patients with asthma as a result of the cys-LTs overgeneration [44].…”