Book ChapterDOI
Myeloperoxidase (MPO): Do We Need Inhibitors?
Rajagopal Desikan,Rajagopal Desikan,Chandrakala Aluganti Narasimhulu,Bobby Khan,Sanjay Rajagopalan,Sampath Parthasarathy +5 more
- pp 535-571
TLDR
Current efforts toward the development of suitable inhibitors using small organic molecules, unexplored organometallic scaffolds, utilization of aptamers as myeloperoxidase inhibitor and future perspective on the scope of therapeutic intervention for this attractive target are critically analyzed.Abstract:
Neutrophils, monocytes and selected tissue macrophages are the predominant sources of myeloperoxidase (MPO). Under physiological chloride concentration, the MPO hemo protein can catalyze the reaction of formation of hypochlorous acid in presence of another oxidant, hydrogen peroxide. MPO-mediated oxidants play a significant part in the inflammatory response, though, the MPO is traditionally viewed as an unspecific microbicidal enzyme and some intermediates are important for immune defense system against invading pathogens. Inflammation plays a lead role in the manifestation and the amelioration of atherosclerosis and other cardiovascular diseases. Hence, there is continuing interest on MPO as a target in the diagnosis and development of potent therapeutic aid against this oxidative enzyme. The necessity of developing a drug to inhibit MPO is getting steady momentum and through this review, we assess the current status of the literature on the source of MPO, its primary physiological role, currently available inhibitors and application of in silico screening, harmful effects on the increased levels of MPO and its implication in multiple disease progression. We critically analyze current efforts toward the development of suitable inhibitors using small organic molecules, unexplored organometallic scaffolds, utilization of aptamers as myeloperoxidase inhibitor and future perspective on the scope of therapeutic intervention for this attractive target.read more
Citations
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Journal ArticleDOI
Synthetic Guaiacol Derivatives as Promising Myeloperoxidase Inhibitors Targeting Atherosclerotic Cardiovascular Disease.
Jayaraj Premkumar,Parthasarathy Sampath,Rajagopalan Sanjay,Aluganti Narashimhulu Chandrakala,Desikan Rajagopal,Desikan Rajagopal +5 more
TL;DR: It is revealed that there is great potential for guaiacol derivatives as therapeutics for CVD by modulating lipid profiles, reducing atherosclerotic plaque burden, and subsequently optimizing cardiovascular functions.
Journal ArticleDOI
Alendronate sodium-polymeric nanoparticles display low toxicity in gastric mucosal of rats and Ofcol II cells
Bruno Iles,Isabela Ribeiro de Sá Guimarães Nolêto,Flaviane de França Dourado,Fábio de Oliveira Silva Ribeiro,Alyne Rodrigues de Araújo,Taiane Maria de Oliveira,Jessica Maria Teles Souza,Ayslan Batista Barros,Gabrielle Costa Sousa,Antônia Carla de Jesus Oliveira,Conceição da Silva Martins,Mariana de Oliveira Viana Veras,Renata Ferreira de Carvalho Leitão,José Roberto S. A. Leite,Durcilene Alves da Silva,Jand Venes R. Medeiros +15 more
TL;DR: The biological tests demonstrated that the alendronate sodium nanoformulation reversed the gastric lesions, maintain the normal levels of malondialdehyde and myeloperoxidase, and showed no toxicity in murine osteoblastic cells, even at high concentrations.
Journal Article
Molecular analysis of the human myeloperoxidase promoter region
TL;DR: Tissue specificity of MPO promoter fragments was determined in myeloid cells arrested either before induction ofMPO expression, during MPO expression (HL60), or after it had ceased (U937), as well as in non-MPO expressing non-myeloids cells.
References
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Journal ArticleDOI
Alternative Activation of Macrophages: Mechanism and Functions
TL;DR: In this paper, the authors assess recent research in this field, argue for a restricted definition, and explore pathways by which the T helper 2 (Th2) cell cytokines interleukin-4 (IL-4) and IL-13 mediate their effects on macrophage cell biology, their biosynthesis, and responses to a normal and pathological microenvironment.
Journal ArticleDOI
Plant Polyphenols as Dietary Antioxidants in Human Health and Disease
TL;DR: It is suggested that long term consumption of diets rich in plant polyphenols offer protection against development of cancers, cardiovascular diseases, diabetes, osteoporosis and neurodegenerative diseases.
Journal ArticleDOI
Myeloperoxidase: friend and foe
TL;DR: It is concluded that the MPO system plays an important role in the microbicidal activity of phagocytes and the role of theMPO system in tissue injury.
Journal ArticleDOI
Polyphenols: antioxidants and beyond
TL;DR: This supplemental issue of The American Journal of Clinical Nutrition offers an overview of the experimental, clinical, and epidemiologic evidence of the effects of polyphenols on health.
Journal ArticleDOI
Myeloperoxidase, a catalyst for lipoprotein oxidation, is expressed in human atherosclerotic lesions.
TL;DR: Findings identify myeloperoxidase as a component of human vascular lesions and suggest that this heme protein can generate reactive species that damage lipids and proteins may contribute to atherogenesis by catalyzing oxidative reactions in the vascular wall.