Preventive Effect of Aspirin Eugenol Ester on Thrombosis in κ-Carrageenan-Induced Rat Tail Thrombosis Model

• Published in: PloS one Vol. 10; no. 7; p. e0133125
• Main Authors: Ma, Ning, Liu, Xi-Wang, Yang, Ya-Jun, Li, Jian-Yong, Mohamed, Isam, Liu, Guang-Rong, Zhang, Ji-Yu
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.07.2015; Public Library of Science (PLoS)
• Subjects: Adenosine; Adenosine diphosphate; Adenosine Diphosphate - toxicity; Agglomeration; Animals; Aspirin; Aspirin - analogs & derivatives; Aspirin - therapeutic use; Atherosclerosis; Blood; Blood clots; Blood coagulation; Blood platelets; Blood Platelets - cytology; Carboxymethyl cellulose; Carboxymethylcellulose; Cardiovascular disease; Carrageenan; Carrageenan - toxicity; Cellulose; Clotting; Disease Models, Animal; Drugs; Erythrocyte Count; Erythrocytes; Erythrocytes - cytology; Eugenol; Eugenol - analogs & derivatives; Eugenol - therapeutic use; Fibrinogen - analysis; Hematocrit; Hemoglobin; Hemoglobins - metabolism; Inflammation; Laboratory animals; Male; Metabolism; Metabolites; Mortality; Pharmaceutical sciences; Physiology; Platelet aggregation; Platelet Aggregation Inhibitors - therapeutic use; Platelet Count; Preventive medicine; Prothrombin Time; Rats; Rats, Wistar; Side effects; Sodium; Sodium carboxymethyl cellulose; Studies; Thromboembolism; Thrombosis; Thrombosis - drug therapy; Thrombosis - etiology; Thrombosis - prevention & control
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0133125

Based on the prodrug principle, aspirin eugenol ester (AEE) was synthesized, which can reduce the side effects of aspirin and eugenol. As a good candidate for new antithrombotic and anti-inflammatory medicine, it is essential to evaluate its preventive effect on thrombosis. Preventive effect of AEE was investigated in κ-carrageenan-induced rat tail thrombosis model. AEE suspension liquids were prepared in 0.5% sodium carboxymethyl cellulose (CMC-Na). AEE was administrated at the dosage of 18, 36 and 72 mg/kg. Aspirin (20 mg/kg), eugenol (18 mg/kg) and 0.5% CMC-Na (30 mg/kg) were used as control drug. In order to compare the effects between AEE and its precursor, integration of aspirin and eugenol group (molar ratio 1:1) was also designed in the experiment. After drugs were administrated intragastrically for seven days, each rat was injected intraperitoneally with 20 mg/kg BW κ-carrageen dissolved in physiological saline to induce thrombosis. The length of tail-thrombosis was measured at 24 and 48 hours. The blank group just was given physiological saline for seven days without κ-carrageenan administrated. The results indicated that AEE significantly not only reduced the average length of thrombus, PT values and FIB concentration, but also reduced the red blood cell (RBC), hemoglobin (HGB), hematocrit (HCT) and platelet (PLT). The effects of AEE on platelet aggregation and anticoagulant in vitro showed that AEE could inhibit adenosine diphosphate (ADP)-induced platelet aggregation as dose-dependence but no notable effect on blood clotting. From these results, it was concluded that AEE possessed positive effect on thrombosis prevention in vivo through the reduction of FIB, PLT, inhibition of platelet aggregation and the change of TT and PT values.