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Preparation and characterization of a novel aspirin derivative with anti-thrombotic and gastric mucosal protection properties.

Zhen XE, Zong M, Gao SN, Cao YG, Jiang L, Chen SX, Wang K, Sun SQ, Peng HS, Bai YH, Li S - PLoS ONE (2014)

Bottom Line: The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa.The derivative was named Ca-ASP.Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.

ABSTRACT
The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca(2+)). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

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Related in: MedlinePlus

Effect of ASP and Ca-ASP on gastric mucosa of rats.(A) Photographs taken from microscopic examination of the gastric mucosa of mice underwent different treatments. (B) Comparison of the median ulcer index obtained for the gastric mucosa.
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pone-0098513-g007: Effect of ASP and Ca-ASP on gastric mucosa of rats.(A) Photographs taken from microscopic examination of the gastric mucosa of mice underwent different treatments. (B) Comparison of the median ulcer index obtained for the gastric mucosa.

Mentions: The extents of damage caused to the gastric mucosal surface by ASP and Ca-ASP were examined microscopically and assigned a score of median ulcer index. Compared to control rats, the mucosal surface of mice administered Ca-ASP exhibited slight damage, which was visible to the naked eyes, and was assigned a gastric damage score of 2 (Figure 7). Rats administered ASP on the other hand showed extensive sign of damage to the gastric mucosal surface, with patches of bleeding. The level of gastric mucosal damage in these animals was assigned a gastric damage score of 12.5. The reduction in gastric damage produced by Ca-ASP was significant, and this indicated that Ca-ASP had much less side effect than pure ASP.


Preparation and characterization of a novel aspirin derivative with anti-thrombotic and gastric mucosal protection properties.

Zhen XE, Zong M, Gao SN, Cao YG, Jiang L, Chen SX, Wang K, Sun SQ, Peng HS, Bai YH, Li S - PLoS ONE (2014)

Effect of ASP and Ca-ASP on gastric mucosa of rats.(A) Photographs taken from microscopic examination of the gastric mucosa of mice underwent different treatments. (B) Comparison of the median ulcer index obtained for the gastric mucosa.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4043976&req=5

pone-0098513-g007: Effect of ASP and Ca-ASP on gastric mucosa of rats.(A) Photographs taken from microscopic examination of the gastric mucosa of mice underwent different treatments. (B) Comparison of the median ulcer index obtained for the gastric mucosa.
Mentions: The extents of damage caused to the gastric mucosal surface by ASP and Ca-ASP were examined microscopically and assigned a score of median ulcer index. Compared to control rats, the mucosal surface of mice administered Ca-ASP exhibited slight damage, which was visible to the naked eyes, and was assigned a gastric damage score of 2 (Figure 7). Rats administered ASP on the other hand showed extensive sign of damage to the gastric mucosal surface, with patches of bleeding. The level of gastric mucosal damage in these animals was assigned a gastric damage score of 12.5. The reduction in gastric damage produced by Ca-ASP was significant, and this indicated that Ca-ASP had much less side effect than pure ASP.

Bottom Line: The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa.The derivative was named Ca-ASP.Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.

ABSTRACT
The use of acetylsalicylic acid (ASP) is limited by its adverse effects, especially the effect on the gastric mucosa. To address this problem, we synthesized a derivative form of ASP, prepared by modification of ASP with nano-hydroxyapatite (a kind of inorganic particle containing Ca(2+)). The derivative was named Ca-ASP. Structural study showed that Ca-ASP was a kind of carboxylate containing intramolecular hydrogen bonds. Rats given a high dose of Ca-ASP (5 mmol per kg body weight) showed similar anti-thrombotic activity as those given the same dose of ASP, but had much lower gastric mucosal damage than ASP (UI: 2 versus UI: 12.5). These rats also showed reduced expression of COX-2, but their COX-1 expression was similar to that of control rats, but significantly higher than that of ASP-administered rats. Furthermore, the level of prostaglandin E2 (PGE2) was up-regulated in Ca-ASP-administered rats compared to ASP-administered rats. Taken together, the results showed that Ca-ASP possessed similar antithrombotic activity as ASP but without the side effect associated with ASP, and the underlying mechanism may center on inhibiting COX-2 without inhibiting COX-1, and thus favouring the production of PGE2, the prostaglandin that plays a vital role in the suppression of platelet aggregation and thrombosis, as well as in the repair of gastric damage.

Show MeSH
Related in: MedlinePlus