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Pharmacological Assessment of Ibuprofen Arginate on Platelet Aggregation and Colon Cancer Cell Killing

Pharmacological Assessment of Ibuprofen Arginate on Platelet Aggregation and Colon Cancer Cell Killing

B Ahmetaj-Shala, A Tesfai, C Constantinou, R Leszczynski, M V Chan, H Gashaw, G Galaris, S Mazi, T D Warner, N S Kirkby, J A Mitchell

Biochem Biophys Res Commun. 2017 Mar 18;484(4):762-766.

PMID: 28153724

Abstract:

Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen, are amongst the most commonly used medications and produce their anti-inflammatory and analgesic benefits by blocking cyclooxygenase (COX)-2. These drugs also have the potential to prevent and treat cancer and some members of the class including ibuprofen can produce anti-platelet effects. Despite their utility, all NSAIDs are associated with increased risk of cardiovascular side effects which our recent work suggests could be mediated by increased levels of the endogenous NO synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) leading to reduced endothelial NOS activity and associated endothelial cell dysfunction. ADMA is a cardiotoxic hormone and biomarker of cardiovascular risk whose effects can be prevented by l-arginine. The ibuprofen salt, ibuprofen arginate (Spididol®) was created to increase drug solubility but we have previously established that it not only effectively blocks COX-2 but also provides an arginine source able to reverse the effects of ADMA in vitro and in vivo. Here we have gone on to explore whether the formulation of ibuprofen with arginine influences the potency and efficacy of the parent molecule using a range of simple in vitro assays designed to test the effects of NSAIDs on (i) platelet aggregation and (iii) colon cancer cell killing. Our findings demonstrate that ibuprofen arginate retains these key functional effects of NSAIDs with similar or increased potency compared to ibuprofen sodium, further illustrating the potential of ibuprofen arginate as an efficacious drug with the possibility of improved cardiovascular safety.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP57469826	Ibuprofen Arginate		57469-82-6	Price

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