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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

XRD spectra of ASP and Ca-ASP.
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pone-0098513-g002: XRD spectra of ASP and Ca-ASP.

Mentions: The spectra of ASP and Ca-ASP obtained from XRD analysis are shown in Figure 2. In the case of ASP spectrum, five main peaks with 2θ values of 7.7°, 15.6°,20.6°, 22.6° and 27.07°, corresponding to the characteristic crystal planes of ASP (100, 002, 012, 211, 310) [23], and the first four of these peaks were also present in the spectrum of Ca-ASP. However, the peak of 27.07° was absent in the spectrum of Ca-ASP and noticeable change in intensity occurred at 7.7° and 15.6°, which became stronger and weaker, respectively, compared to the spectrum of ASP. The spectrum of Ca-ASP also yielded five different peaks: 2θ values of 25.9°, 28.1°, 28.9°, 31.5°, and 32.9° corresponding to the (002), (102), (210), (211) and (112) crystal planes of hydroxyapatite [24]. Additional peak was also present at 22.6° in the spectrum of Ca-ASP. The XDR spectrum of Ca-ASP indicated that Ca-ASP was not simply a mixture of ASP and Hap, but was in fact a distinct crystal structure formed by reaction of ASP with Hap [25].


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)

XRD spectra of ASP and Ca-ASP.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098513-g002: XRD spectra of ASP and Ca-ASP.
Mentions: The spectra of ASP and Ca-ASP obtained from XRD analysis are shown in Figure 2. In the case of ASP spectrum, five main peaks with 2θ values of 7.7°, 15.6°,20.6°, 22.6° and 27.07°, corresponding to the characteristic crystal planes of ASP (100, 002, 012, 211, 310) [23], and the first four of these peaks were also present in the spectrum of Ca-ASP. However, the peak of 27.07° was absent in the spectrum of Ca-ASP and noticeable change in intensity occurred at 7.7° and 15.6°, which became stronger and weaker, respectively, compared to the spectrum of ASP. The spectrum of Ca-ASP also yielded five different peaks: 2θ values of 25.9°, 28.1°, 28.9°, 31.5°, and 32.9° corresponding to the (002), (102), (210), (211) and (112) crystal planes of hydroxyapatite [24]. Additional peak was also present at 22.6° in the spectrum of Ca-ASP. The XDR spectrum of Ca-ASP indicated that Ca-ASP was not simply a mixture of ASP and Hap, but was in fact a distinct crystal structure formed by reaction of ASP with Hap [25].

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