Role of Surface-Active Phospholipids in Gastric Cytoprotection

Lichtenberger, Lenard M.; Graziani, Lynne A.; Dial, Elizabeth J.; Butler, Bruce D; Hills, B. A.

doi:10.1126/science.6828859

Cited by 286 publications

(108 citation statements)

References 27 publications

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“…nism (20)(21)(22), but these effects are not without controversy (23,24). Mersereau and Hinchey (25) proposed that dissolution of the mucosal folds may be associated with the prevention of necrotic gastric lesions along the fold crests in the stomach after exposure to necrotizing agents.…”

Section: Discussionmentioning

confidence: 99%

Roles of gastric motility changes in cytoprotection induced by acetazolamide and cysteamine in rats.

et al. 1987

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Abstract-The present study was undertaken using acetazolamide (AZ) and cyste amine (Cys) to investigate the relationship between gastric motor activity and the phenomenon of "cytoprotection" in rats. Both AZ (10-100 mg/kg) and Cys (10-100 mg/kg), given either p.o. or s.c., significantly reduced the formation of gastric mucosal injury caused by HCI-ethanol (1 ml of 60% ethanol in 150 mM HCI, p.o.). The protective effect of Cys appeared within 10 min, reached the maximal levels 30 min later, while that of AZ appeared from 30 min after administration and became potent with a latency period after treatment. Neither indomethacin (IM: 5 mg/kg, s.c.) nor N-ethylmaleimide (NEM: 5 mg/kg, s.c.) significantly affected the protective effect of Cys, whereas that of AZ was almost totally antagonized by IM. Both AZ and Cys, given either intragastrically or s.c., significantly inhi bited gastric motor activity measured as intraluminal pressure recordings, but had minimal effect on acid and alkaline secretion. IM significantly attenuated the inhibitory effect of AZ on the motor activity, while NEM did not affect the inhibited motor responses caused by AZ and Cys. A significant relationship was found between the inhibitory effects of these two drugs on gastric motor activity and HCI-ethanol-induced mucosal injury, the correlation coefficient being 0.819 (P< 0.01). When the mucosal folds were visualized with Gentian Violet (1 ml of 0.5% v/v, p.o.), both AZ and Cys significantly prevented the localized staining along the mucosal folds, suggesting dissolution of the folds. These results suggest that both AZ and Cys protect the gastric mucosa against injury caused by HCI-ethanol, probably through a dissolution of mucosal folds due to inhibition of gastric motor activity.

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Section: Discussionmentioning

confidence: 99%

Roles of gastric motility changes in cytoprotection induced by acetazolamide and cysteamine in rats.

et al. 1987

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“…For example, association of NSAIDs with phospholipids has been suggested to improve GI safety of these drugs (3). The presence of an adsorbed layer of surface-active phospholipids on the surface of the mucus that covers the surface epithelium is suggested to protect the GI tissues by providing a hydrophobic layer between the epithelium and the luminal contents (4,5). It has been reported that NSAIDs associated with zwitterionic phospholipids may reduce GI toxicity (3).…”

mentioning

confidence: 99%

Development and physicochemical evaluation of pharmacosomes of diclofenac

Semalty¹,

Semalty²,

Singh³

et al. 2009

Acta Pharmaceutica

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Diclofenac is one of the most widely prescribed non-steroidal anti-inflammatory drugs (NSAIDs). Use of diclofenac is associated with two major limitations; first, rare, but serious and sometimes fatal, gastrointestinal (GI) side-effects, including ulceration, and hemorrhage, especially in the elderly (1, 2), and second, poor water solubility. Pharmacosomes are amphiphilic lipid vesicular systems that have shown their potential in improving the bioavailability of poorly water soluble as well as poorly lipophilic drugs. Diclofenac is a poorly water soluble drug and also causes gastrointestinal toxicity. To improve the water solublity of diclofenac, its pharmacosomes (phospholipid complex) have been prepared and evaluated for physicochemical analysis. Diclofenac was complexed with phosphatidylcholine (80 %) in equimolar ratio, in the presence of dichloromethane, by the conventional solvent evaporation technique. Pharmacosomes thus prepared were evaluated for drug solubility, drug content, surface morphology (by scanning electron microscopy), phase transition behaviour (by differential scanning calorimetry), crystallinity (by X-ray powder diffraction) and in vitro dissolution. Pharmacosomes of diclofenac were found to be irregular or disc shaped with rough surfaces in SEM. Drug content was found to be 96.2 ± 1.1 %. DSC thermograms and XRPD data confirmed the formation of the phospholipid complex. Water solubility of the prepared complex was found to be 22.1 mg mL -1 as compared to 10.5 mg mL -1 of diclofenac. This improvement in water solubility in prepared pharmacosomes may result in improved dissolution and lower gastrointestinal toxicity. Pharmacosomes showed 87.8 % while the free diclofenac acid showed a total of only 60.4 % drug release at the end of 10 h of dissolution study.

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“…Submicron emulsions as a novel system to reduce the hemolytic effect, its mechanism of the protective effect was reported as follows: The first theory by Lichtenberger et al 25) suggested that phospholipids protect membranes by being adsorbed as a monolayer onto the surface, thereby creating a hydrophobic barrier which results in a reduction of hemolysis. The second theory by Martin et al 26,27) correlated this behavior to the protective function of phospholipids themselves, as they were able to form mixed micelles with the other molecules as a complex.…”

Section: In Vivomentioning

confidence: 99%