A new ibuprofen derivative inhibits platelet aggregation and ros mediated platelet apoptosis

Rakesh, K. S. and Jagadish, S. and Vinayaka, A. C. and Hemshekhar, M. and Paul, M. and Thushara, R. M. and Sundaram, M. S. and Swaroop, T. R. and Mohan, C. D. and Basappa and Sadashiva, M. P. and Kemparaju, K. and Girish, K. S. and Rangappa, K. S. (2014) A new ibuprofen derivative inhibits platelet aggregation and ros mediated platelet apoptosis. PLoS ONE, 9 (9). e2718. ISSN 1932-6203

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Abstract

Thrombocytopenia is a serious issue connected with the pathogenesis of several human diseases including chronic inflammation, arthritis, Alzheimer's disease, cardiovascular diseases (CVDs) and other oxidative stress-associated pathologies. The indiscriminate use of antibiotics and other biological drugs are reported to result in thrombocytopenia, which is often neglected during the treatment regime. In addition, augmented oxidative stress induced by drugs and pathological conditions has also been shown to induce thrombocytopenia, which seems to be the most obvious consequence of elevated rate of platelet apoptosis. Thus, blocking oxidative stress-induced platelet apoptosis would be of prime importance in order to negotiate thrombocytopenia and associated human pathologies. The current study presents the synthesis and platelet protective nature of novel ibuprofen derivatives. The potent anti-oxidant ibuprofen derivative 4f was selected for the study and the platelet protective efficacy and platelet aggregation inhibitory property has been demonstrated. The compound 4f dose dependently mitigates the oxidative stress-induced platelet apoptosis in both platelet rich plasma and washed platelets. The platelet protective nature of compound 4f was determined by assessing various apoptotic markers such as ROS generation, cytosolic Ca2+levels, PS externalization, cytochrome C translocation, Caspase activation, mitochondrial membrane depolarization, cytotoxicity, LDH leakage and tyrosine phosphorylation of cytosolic proteins. Furthermore, compound 4f dose dependently ameliorated agonist induced platelet aggregation. Therefore, compound 4f can be estimated as a potential candidate in the treatment regime of pathological disorders associated with platelet activation and apoptosis. In addition, compound 4f can be used as an auxiliary therapeutic agent in pathologies associated with thrombocytopenia.

Item Type:	Article
Uncontrolled Keywords:	apoptosis, Article, controlled study, drug synthesis, human, human cell, unclassified drug, analogs and derivatives, chemistry, cytotoxicity, Humans, dose response, Dose-Response Relationship, Drug, metabolism, protein phosphorylation, cytology, human tissue, Apoptosis, reactive oxygen metabolite, Reactive Oxygen Species, oxidative stress, Oxidative Stress, Blood Platelets, thrombocyte, thrombocyte activation, lactate dehydrogenase, ibuprofen, protein transport, thrombocyte aggregation inhibition, drug effects, enzyme activation, cell protection, quercetin, thrombocyte aggregation, Platelet Aggregation, 2 4 2 methylpropyl]phenyl] n' (phenylsulfonyl)propanehydrazide, 5 dichlorophenyl]sulfonyl] 2 4 2 methylpropyl]phenyl]propanehydrazide, calcimycin, calcium ion, caspase, cytochrome c, Ibuprofen, ibuprofen derivative, membrane depolarization, mitochondrial membrane, n' 2, n' 4 bromophenyl]sulfonyl] 2 4 2 methylpropyl]phenyl]propanehydrazide, n' 4 fluorophenyl]sulfonyl] 2 4 2 methylpropyl]phenyl]propanehydrazide, n' 4 methoxyphenyl]sulfonyl] 2 4 2 methylpropyl]phenyl]propanehydrazide, n' 4 nitrophenyl]sulfonyl] 2 4 2 methylpropyl]phenyl]propanehydrazide, phosphatidylserine, thrombocyte rich plasma, thrombocytopenia
Subjects:	C Chemical Science > Biochemistry C Chemical Science > Chemistry
Divisions:	Department of > Biochemistry Department of > Chemistry
Depositing User:	Arshiya Kousar Library Assistant
Date Deposited:	31 Aug 2019 05:15
Last Modified:	31 Aug 2019 05:15
URI:	http://eprints.uni-mysore.ac.in/id/eprint/4294

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