ABSTRACT
BACKGROUND/AIMS: Phosphatidylcholine (PC)-derived choline exhibits anti-inflammatory properties in stress conditions. Phosphatidylethanolamine (PE) and N-acylphosphatidylethanolamines (NAPEs) are endogenous bioactive phospholipids linked to the PC and endocannabinoid metabolisms. We hypothesized that an increased dietary input of PC, PE and NAPE may interfere with leukocyte reactions and thus decreases the inflammatory activation. METHODS: CFLP mice were fed with a control diet or with a diet supplemented with 1% PC, 0.4% PE and 0.1% NAPE for 7 days before the induction of pleurisy with carrageenan. Pleural leukocyte migration, pulmonary mast cell degranulation (Alcian blue-safranin O staining), and the activities of inducible nitric oxide synthase, xanthine oxidoreductase and myeloperoxidase were determined in lung tissue biopsies. RESULTS: The carrageenan-induced inflammatory response was characterized by pulmonary leukocyte infiltration, mast cell degranulation and significantly increased inducible nitric oxide synthase and xanthine oxidoreductase activities (by 82 and 60%, respectively). Treatment of mice with acetylsalicylic acid or with dietary PC + PE + NAPE supplementation significantly decreased the leukocyte reaction, and suppressed the activity of the pulmonary proinflammatory enzymes. CONCLUSION: This study confirms a potential for dietary PC + PE + NAPE supplementation to influence events crucial for the remission of acute inflammation. PC + PE + NAPE administration could possibly be a novel preventive or pharmacotherapeutic option in inflammatory pathologies.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Lecithins/administration & dosage , Phosphatidylethanolamines/administration & dosage , Pleurisy/diet therapy , Animals , Carrageenan/toxicity , Cell Degranulation , Dietary Supplements , Inflammation/diet therapy , Inflammation/etiology , Inflammation/pathology , Leukocytes/pathology , Lung/enzymology , Lung/pathology , Male , Mast Cells/pathology , Mast Cells/physiology , Mice , Nitric Oxide Synthase Type II/metabolism , Peroxidase/metabolism , Pleurisy/etiology , Pleurisy/pathology , Xanthine Dehydrogenase/metabolismABSTRACT
BACKGROUND: Acetylsalicylic acid (ASA)-induced gastric injury is reduced when ASA is administered along with phosphatidylcholine. The hydrolysis of endogenous phosphatidylcholine leads to the production of betaine, which may participate in the maintenance of cellular homeostasis. The present aims were to investigate the effects of exogenous betaine and its palmitic acid complex (betaine-palmitate) in the protection of the gastric mucosa in ASA-induced subacute damage. METHODS: Repeated doses of ASA were given intragastrically to male Wistar rats. Control rats were given vehicle only, while treated animals were challenged with ASA or with ASA along with betaine, palmitic acid or betaine-palmitate. The gastric mucosa was examined after 3 days and the nature of any microscopic mucosal injury was assessed by histology. The extent of macroscopic damage, changes in permeability (assessed by Evans blue method) and tissue ATP concentrations were determined in separate series. RESULTS: ASA induced a significant fall in the ATP content of the mucosa, which was not affected by the other drugs used in the study. However, the ASA-induced mucosal permeability increase could be completely reversed by betaine-palmitate supplementation. The extent of severity of the macroscopic and microscopic lesions was 33% and 2.45, respectively, for ASA, as compared with 15% and 2.2 for betaine, 14% and 1.9 for palmitic acid and 3% and 1.4 for betaine-palmitate. CONCLUSIONS: Betaine-palmitate affords a significant protective effect against ASA-induced injury, without influencing the ATP synthesis, and this suggests that the defence is due to its ability to prevent secondary damage.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/adverse effects , Aspirin/adverse effects , Betaine/therapeutic use , Gastrointestinal Agents/therapeutic use , Palmitic Acid/therapeutic use , Palmitic Acids/therapeutic use , Peptic Ulcer/chemically induced , Peptic Ulcer/prevention & control , Animals , Betaine/analogs & derivatives , Drug Combinations , Gastric Mucosa/drug effects , Male , Phosphatidylcholines/metabolism , Phosphatidylcholines/therapeutic use , Rats , Rats, Wistar , Severity of Illness IndexABSTRACT
The effect of co-administration with polyene phosphatidylcholine (Phospholipon 100) on the oral gastrotoxicity of various non-steroidal anti-inflammatory drugs (NSAIDs) was studied in the rat. The highly unsaturated phospholipid reduced gastric mucosal lesions measured 3.5 h after oral administration of aspirin, indomethacin, phenylbutazone, diclofenac, piroxicam and sudoxicam to rats which had received a 3 day bread diet followed by 24 h fasting. The extent of reduction of gastrotoxicity varied amongst the individual NSAIDs. Phospholipon 100 also reduced gastric lesions induced by 3 day oral piroxicam and diclofenac administration. A trend towards reduction of oral diclofenac gastrotoxicity was observed following intravenous Phospholipon 100 administration. Phospholipon 100 H (100% saturated phosphatidylcholine) was less effective than Phospholipon 100 in improving acute gastric tolerance to oral phenylbutazone, diclofenac and piroxicam. Administration of the NSAID-Phospholipon 100 combination produced little change in the anti-inflammatory activities of diclofenac on carrageenan paw oedema and diclofenac and piroxicam on adjuvant arthritis in the rat. Combination with Phospholipon 100 offers a novel means for reducing the gastric side-effects of NSAID therapy.