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A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis

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 biologi...

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Autores principales: Rakesh, Kodagahalli S., Jagadish, Swamy, Vinayaka, Ajjampura C., Hemshekhar, Mahadevappa, Paul, Manoj, Thushara, Ram M., Sundaram, Mahalingam S., Swaroop, Toreshettahally R., Mohan, Chakrabhavi D., Basappa, Sadashiva, Marilinganadoddi P., Kemparaju, Kempaiah, Girish, Kesturu S., Rangappa, Kanchugarakoppal S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169656/
https://www.ncbi.nlm.nih.gov/pubmed/25238069
http://dx.doi.org/10.1371/journal.pone.0107182
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author Rakesh, Kodagahalli S.
Jagadish, Swamy
Vinayaka, Ajjampura C.
Hemshekhar, Mahadevappa
Paul, Manoj
Thushara, Ram M.
Sundaram, Mahalingam S.
Swaroop, Toreshettahally R.
Mohan, Chakrabhavi D.
Basappa,
Sadashiva, Marilinganadoddi P.
Kemparaju, Kempaiah
Girish, Kesturu S.
Rangappa, Kanchugarakoppal S.
author_facet Rakesh, Kodagahalli S.
Jagadish, Swamy
Vinayaka, Ajjampura C.
Hemshekhar, Mahadevappa
Paul, Manoj
Thushara, Ram M.
Sundaram, Mahalingam S.
Swaroop, Toreshettahally R.
Mohan, Chakrabhavi D.
Basappa,
Sadashiva, Marilinganadoddi P.
Kemparaju, Kempaiah
Girish, Kesturu S.
Rangappa, Kanchugarakoppal S.
author_sort Rakesh, Kodagahalli S.
collection PubMed
description 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 Ca(2+) 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.
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spelling pubmed-41696562014-09-22 A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis Rakesh, Kodagahalli S. Jagadish, Swamy Vinayaka, Ajjampura C. Hemshekhar, Mahadevappa Paul, Manoj Thushara, Ram M. Sundaram, Mahalingam S. Swaroop, Toreshettahally R. Mohan, Chakrabhavi D. Basappa, Sadashiva, Marilinganadoddi P. Kemparaju, Kempaiah Girish, Kesturu S. Rangappa, Kanchugarakoppal S. PLoS One Research Article 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 Ca(2+) 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. Public Library of Science 2014-09-19 /pmc/articles/PMC4169656/ /pubmed/25238069 http://dx.doi.org/10.1371/journal.pone.0107182 Text en © 2014 Rakesh et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Rakesh, Kodagahalli S.
Jagadish, Swamy
Vinayaka, Ajjampura C.
Hemshekhar, Mahadevappa
Paul, Manoj
Thushara, Ram M.
Sundaram, Mahalingam S.
Swaroop, Toreshettahally R.
Mohan, Chakrabhavi D.
Basappa,
Sadashiva, Marilinganadoddi P.
Kemparaju, Kempaiah
Girish, Kesturu S.
Rangappa, Kanchugarakoppal S.
A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis
title A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis
title_full A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis
title_fullStr A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis
title_full_unstemmed A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis
title_short A New Ibuprofen Derivative Inhibits Platelet Aggregation and ROS Mediated Platelet Apoptosis
title_sort new ibuprofen derivative inhibits platelet aggregation and ros mediated platelet apoptosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4169656/
https://www.ncbi.nlm.nih.gov/pubmed/25238069
http://dx.doi.org/10.1371/journal.pone.0107182
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