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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

Analysis of platelet counts and COX-2 expression.(A) Platelet counts of rats underwent different treatments. (B) Western blot analysis of COX-2 expression in rats underwent different treatments.
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pone-0098513-g006: Analysis of platelet counts and COX-2 expression.(A) Platelet counts of rats underwent different treatments. (B) Western blot analysis of COX-2 expression in rats underwent different treatments.

Mentions: Platelet count was used as an index for anti-thrombotic activity [26]. The result of platelet count is shown in Figure 6A. Rats administered ASP (pure aspirin) or Ca-ASP all had lower platelet counts than control rats. The highest level of anti-thrombotic activity was seen in the group given ASP, as shown by its lowest platelet count. At the other end of the spectrum, the control had the lowest level of anti-thrombotic activity, as seen from its highest platelet count. The difference in platelet count between these two groups was significant (P<0.01). The platelet counts of rats administered different doses of Ca-ASP were also lower than that of control rat. However, only those administered moderate (Ca-ASP/M) or high (Ca-ASP/H) dosage had significantly lower platelet counts than the control. Rats given low dosage of Ca-ASP showed no significant decrease in platelet count compared to the control. Among the three groups that received Ca-ASP, only the group receiving a high dose attained comparable platelet count with the group given ASP. These results showed that a moderate dose of Ca-ASP could increase the level of antithrombotic activity, but only by increasing the dose to that of ASP (0.5 mmol/kg) would the enhancement of antithrombotic activity achieved by Ca-ASP reach a similar level as that produced by 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)

Analysis of platelet counts and COX-2 expression.(A) Platelet counts of rats underwent different treatments. (B) Western blot analysis of COX-2 expression in rats underwent different treatments.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0098513-g006: Analysis of platelet counts and COX-2 expression.(A) Platelet counts of rats underwent different treatments. (B) Western blot analysis of COX-2 expression in rats underwent different treatments.
Mentions: Platelet count was used as an index for anti-thrombotic activity [26]. The result of platelet count is shown in Figure 6A. Rats administered ASP (pure aspirin) or Ca-ASP all had lower platelet counts than control rats. The highest level of anti-thrombotic activity was seen in the group given ASP, as shown by its lowest platelet count. At the other end of the spectrum, the control had the lowest level of anti-thrombotic activity, as seen from its highest platelet count. The difference in platelet count between these two groups was significant (P<0.01). The platelet counts of rats administered different doses of Ca-ASP were also lower than that of control rat. However, only those administered moderate (Ca-ASP/M) or high (Ca-ASP/H) dosage had significantly lower platelet counts than the control. Rats given low dosage of Ca-ASP showed no significant decrease in platelet count compared to the control. Among the three groups that received Ca-ASP, only the group receiving a high dose attained comparable platelet count with the group given ASP. These results showed that a moderate dose of Ca-ASP could increase the level of antithrombotic activity, but only by increasing the dose to that of ASP (0.5 mmol/kg) would the enhancement of antithrombotic activity achieved by Ca-ASP reach a similar level as that produced by 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