Plaquex to protect the gastric lining from NSAID effects
As described under What is Plaquex, phosphatidylcholine also plays a role in mono layer membranes such as surfactants. As such it forms a monolayer on the gastric mucosa to form a hydrophobic layer to protect it from gastric juices and NSAID effects. NSAIDs do not only directly irritate the gastrointestinal mucosa but also diminish cytoprotective prostaglandins. PC on the other hand, can be used as a repair element of the hydrophobic layers and provide with its high content in linoleic acid precursors for the local increase of these prostaglandins.
Intragastral co-administration of PC and acetylsalicylic acid (ASA), diclofenac, indomethacin, phenylbutazone, piroxicam or sudoxicam in an acute gastrotoxicity test in the rat showed a pronounced reduction of ulcer formation. PC was more effective at the higher doses in the phosholipid-NSAID combinations1.
To assess a possible systemic protective activity of PC we investigated the effect of i.v. injected PC on diclofenac-induced gastric damage and that of orally administered PC on mucosal PGE2 formation after indomethacin administration2. Three individual studies have shown that tolerance to diclofenac was clearly improved after i.v. PC administration. Mucosal PGE2 synthesis, inhibited by indomethacin administration alone, was significantly increased 60 and 120 minutes after simultaneous treatment with PC.
Using indomethacin, it was shown that simultaneous administration of PC (200 mg/kg) reduced the inhibition of PGE2 generation; a similar effect on 6-keto-PGF1 formation (prostacyclin metabolite) was also detectable. The increase in mucosal leukotriene synthesis after indomethacin and diclofenac administration could be reversed with EPL3.
1 Leyck, S., M.J. Parnham: Counteraction by polyenephosphatidylcholine of diclofenac induced gastric lesions and indometacin impaired mucosal PGE2 generation in rats. Naunyn-Schmiedebergs. Arch. Pharmacol. 329 (1985) R 66
2 Leyck, S. A.M. Hüther, M.H. Parnham: Polyene Phosphatidylcholine: an inhibitor of NSAID gastric toxicity which increases impaired mucosal PGE2 synthesis. 2nd Meeting on Side effects of Anti-Inflammatory Drugs, Cambridge, July 31-August 2, 1985
3 Leyck, S., M.J. Parnham: Inhibition of NSAID gastric toxicity by polyenephosphatidylcholine is associated with increased mucosal PG synthesis. 18th Congr. of Eur. Assoc. for Gastroenter. Endosc,. Berlin March 13-15, 1986