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Abstract

Based on our previous studies that aspirin (ASA) -induced gastric ulceration in rats can be significantly reduced if the drug is chemically associated with phosphatidylcholine (PC), we undertook the present study to compare gastric ulcer healing rates in rats administered either unmodified or PC-complexed ASA. Gastric ulcers were induced in anesthetized rats by briefly exposing the mucosal surface to 0.2 ml 60% acetic acid followed by randomization of the rats to study groups; daily intragastrically administered saline (control), ASA (36, 54 mg/kg), or ASA-PC complex. In contrast to the 65-70% reduction in ulcer size recorded in controls, ulcer healing was significantly retarded in rats administered unmodified ASA. Conversely, the size of the experimentally induced ulcers was less than control values in rats daily administered the PC-associated ASA, suggesting an acceleration in the rate of ulcer healing. Daily intragastric administration of ASA to rats over the study period also resulted in a significant decrease in surface hydrophobicity from control values as measured by contact angle analysis. However, surface hydrophobicity was partially restored in rats administered the PC-complexed ASA. Consistent with these findings, it was determined that ASA-treated rats had a lower hematocrit than control values, as an index of gastrointestinal bleeding, whereas this parameter remained at control levels in rats administered the PC-complexed ASA. We conclude that PC-associated ASA promotes ulcer healing above the values measured in rats treated with ASA or saline. This property may be attributable to the fact that in contrast to unmodified ASA, which aggravates ulcer healing by transforming the stomach to an acid-permeable state, the protective hydrophobic lining of the stomach is maintained in rats administered PC-associated ASA, thereby allowing ulcer healing of the tissue to proceed.

An Overview of Acetic Acid Ulcer Models<br>&mdash;The History and State of the Art of Peptic Ulcer Research&mdash;

“…The enhanced ulcer healing effect of heparin was accompanied by a significant increase in mucosal regeneration and proliferation, angiogenesis, and mucus secretion, without affecting bleeding time. Kurinets and Lichtenberger et al 135) provided a new hypothesis, stating that the mechanism underlying the damaging effect of aspirin for the gastric mucosa might be impairment of the phospholipid layer on the mucosal surface, leading to penetration of hydrochloric acid into the mucosa. Given this hypothesis, the effects of aspirin alone and aspirin chemically associated with phosphatidilcholine (aspirin-PC) on the healing of acetic acid ulcers were examined in rats.…”

Syntheses and cytotoxicity of phosphatidylcholines containing ibuprofen or naproxen moieties

“…Among different approaches to improving drug quality, there has been a huge potential for drugs combined with phospholipids 17–19 . One reason for this is that they are non-toxic and biocompatible.…”

“…One reason for this is that they are non-toxic and biocompatible. Studies that were carried out on animal and human cells indicated that the mixture of NSAIDs and phosphatidylcholine exhibits stronger activity at identical concentrations and lower GI toxicity than NSAIDs alone 19–22 . Moreover, phospholipids with linked drugs mediate the transport of compounds and increase their bioavailability 23 .…”

Advent of Novel Phosphatidylcholine-Associated Nonsteroidal Anti-Inflammatory Drugs with Improved Gastrointestinal Safety

“…We believe this protection is attributable to the maintenance of the defensive hydrophobic barrier of the gastric mucosa. We also observed that the ability of daily aspirin administration to retard the healing of experimentally induced gastric ulcers could be overcome if rats were treated with PC-associated aspirin 52. Related studies using animal models of fever and inflammation indicate that PC-associated NSAIDs had equal or enhanced therapeutic activity, compared with the use of NSAID alone 3,55…”