title: Preparation and characterization of a novel aspirin derivative with anti-thrombotic and gastric mucosal protection properties.
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.
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Xi-E
authors.initials: XE
authors.lastname: Zhen
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Zong
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Sai-Nan
authors.initials: SN
authors.lastname: Gao
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Yong-Gang
authors.initials: YG
authors.lastname: Cao
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Shu-Xin
authors.initials: SX
authors.lastname: Chen
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Kuan
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Shi-Qin
authors.initials: SQ
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Peng
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Yu-Hua
authors.initials: YH
authors.lastname: Bai
authors.affiliation: Department of Pharmaceutics, Daqing Branch, Harbin Medical University, Daqing, China.
authors.forename: Sen
authors.initials: S
authors.lastname: Li
mesh_terms: D000818:Animals; D001241:Aspirin / Q000031:analogs & derivatives / Q000494:pharmacology*; D051545:Cyclooxygenase 1 / Q000235:genetics / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D015232:Dinoprostone / Q000235:genetics / Q000378:metabolism; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone; D001241:Aspirin