ROLE OF NITRIC OXIDE (NO) IN CAPSAICIN MEDIATED ANTI-PLATELET ACTIVITY IN IN VITRO, IN VIVO, EX-VIVO MODEL OF PLATELET AGGREGATION ASSAY AND ARTERIAL THROMBOSIS IN RAT: POTENTIAL THERAPEUTIC TARGET?

Mihir K Patel,Kiranj K Chaudagar,Anita A Mehta

doi:10.22159/ijpps.2018v10i4.22474

Abstract

Objective: Although recent advances in the treatment of congestive heart disease, mortality among patients’ remains a questionable remark. Therefore, we evaluated the role of capsaicin on in vitro and ex vivo platelet aggregation induced by Adenosine Di-Phosphate (ADP) as well as in in vivo thrombosis models and role of NO, KATP was also identified in the capsaicin-induced anti-platelet animal model as well as in vivo model of arterial thrombosis.Methods: According to body weight wistar rats were divided into five groups. Group I and Group II was treated with saline and capsaicin (3 mg/kg, i. v), while animals from Group III were treated with N(ω)-nitro-L-arginine methyl ester (L-NAME) (30 mg/kg, i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group IV animals were treated with glibenclamide (10 mg/kg,i. v) 30 min before administration of capsaicin (3 mg/kg, i. v). Group V was considered as a positive control and administered clopidogrel (30 mg/kg, p. o). Animals were subjected for in vitro, ex-vivo platelet aggregation assay. ADP (30µM) was utilized as an aggregating agent in these experiments. After these assays; animals of each group were subjected for subaqueous tail bleeding time in a rat model and FeCl3-induced arterial thrombosis model in rats.Results: In ADP-induced in vitro platelet aggregation, a significant reduction in % platelet aggregation was observed at 50µM (64.35±4.641) and 100µM (52.72±4.192) concentration of capsaicin as compared to vehicle control (85.82±3.716). Capsaicin (3 mg/kg, i. v) also showed a significant reduction (49.53±4.075) in ex-vivo ADP-induced platelet aggregation as compared to vehicle control (89.38±2.057). In FeCl3 induced arterial thrombosis model, Capsaicin (3 mg/kg, i. v) exhibited an increase in time to occlusion in this rodent model and presence of the L-NAME and glibenclamide had inhibited the activity of capsaicin.Conclusion: In our study, capsaicin (50 µM, 100µM) exhibited potent anti-platelet activity in ADP-induced platelet aggregation, similarly capsaicin exhibited significant anti-platelet action in the ex-vivo study. Moreover, the presence of L-NAME and glibenclamide inhibited the anti-thrombotic and anti-platelet action of capsaicin. Therefore, it was concluded that NO and KATP may be involved in the anti-thrombotic action of capsaicin.

Highlights

Heart attacks and strokes are the most common causes of mortality and morbidity across the world and both represent clinical manifestations of acute arterial thrombosis [1]
It was concluded that Nitric oxide (NO) and KATP may be involved in the anti-thrombotic action of capsaicin
We explored the mechanism of antiplatelet action of capsaicin by using L-NAME and glibenclamide to identify the role of NO and KATP in capsaicin mediated antiplatelet action

Summary

Introduction

Heart attacks and strokes are the most common causes of mortality and morbidity across the world and both represent clinical manifestations of acute arterial thrombosis [1]. Atherosclerosis presents a greater risk to cardiovascular and peripheral vascular system causing mortality in cardiovascular disease patients [2]. It was believed that the platelet is having a minor role in this process; it is recognized that the platelet places itself as a critical link between thrombus formation, inflammation, and atherosclerosis [5]. If the injury continues to happen, it will activate the cascade of signalling molecules which will form thrombus at the site of injury. This will lead to life-threatening disease states such as myocardial infarction, atherosclerosis or ischemic stroke [6]

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Discussion

Conclusion