Objective: The curcumin derivative 3,5-bis(benzylidene)-4-piperidone (EF24) has recently been shown to improve survival and organ physiology in a rat model of hemorrhagic shock (HS). It also inhibits NF-κB transcription factor. Since many inhibitors of NF-κB also suppress platelet function, we investigated whether EF24 also influences platelet function in our rat model. Optimal platelet function is necessary to control blood loss, and a pharmacologic therapy with drugs negatively influencing coagulation process is not desirable. Methods: Male Sprague Dawley rats (250-300 g; n = 22) with indwelling femoral artery catheter were assigned to three groups: (1) control; (2) HS + vehicle; or (3) HS + EF24. Hemorrhagic shock was induced by exsanguination of ∼45% of blood. EF24 drug solution (0.4 mg/kg) or vehicle was administered intraperitoneally immediately after HS and the rats were allowed to freely compensate for hypovolemia. Blood parameters were evaluated at baseline and 0.3, 1, and 6 h after shock. For activated partial thromboplastin time (aPTT), prothrombin time (PT), the blood was collected in 3.2% Na citrate tubes, whereas for hematology, the blood was collected in EDTA tubes. Results: The PT values in the three groups were not significantly different: 23.9 s (control), 22.5 s (HS + vehicle), and 21.6 s (HS + EF24). However, EF24 significantly decrease aPTT in early (t = 20 min) post-hemorrhagic shock period (control 41.8 s, HS + vehicle 40.5 s, and HS + EF24 27.8 s; P <0.05). This effect vanished in samples collected at 1 and 6 h after shock. Plasma glucose and lactate, hematocrit, or CBC parameters among the three groups were not significantly different. Conclusion: These preliminary findings suggest that EF24 may have a suppressive effect on the activation of the intrinsic coagulation pathway. However, the transient nature of this effect only on aPTT is a departure from a prolonged platelet effect of other NF-κB inhibitors on both PT and aPTT.
CITATION STYLE
Croft, B., Hussain, A., Hendrick, A., Galbraith, W., & Awasthi, V. (2015). Hematological analysis of synthetic curcumin derivative, EF24, in a rat model of hypovolemic shock. Journal of the American Pharmacists Association, 55(2), e127. Retrieved from https://www.embase.com/search/results?subaction=viewrecord&id=L71970817&from=export http://dx.doi.org/10.1331/JAPhA.2015.15515
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