Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

Using particulate matter (PM) mass as exposure metric does not reveal the intrinsic PM chemical characteristics or toxic potential, which is crucial for monitoring the sources of emission causing adverse health effects and developing risk mitigating strategies. Oxidative stress and ensuing lipid per...

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Autores principales:	Sumit K. Dey, Kavya Sugur, Venkataramana G. Venkatareddy, Pradhi Rajeev, Tarun Gupta, Rajesh K. Thimmulappa
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Particulate matter Oxidative potential Lipid peroxidation Lung Oxidized phospholipids Medicine (General) R5-920 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/dd0859bf5db14f17b40381050765d38e
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spelling	oai:doaj.org-article:dd0859bf5db14f17b40381050765d38e2021-11-26T04:28:57ZLipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses2213-231710.1016/j.redox.2021.102189https://doaj.org/article/dd0859bf5db14f17b40381050765d38e2021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2213231721003499https://doaj.org/toc/2213-2317Using particulate matter (PM) mass as exposure metric does not reveal the intrinsic PM chemical characteristics or toxic potential, which is crucial for monitoring the sources of emission causing adverse health effects and developing risk mitigating strategies. Oxidative stress and ensuing lipid peroxidation (LPO) in the lung are crucial underlying mechanisms of action by which PM drives cardiorespiratory disease. In the current study, we have postulated and demonstrated that the intrinsic potential of PM to elicit LPO, defined as “LPO index” as a novel approach for characterizing oxidative potential of PM (PMOP) and predicting biological toxicity. First, we exposed unsaturated phosphatidylcholine (PC), an abundant phospholipid in the cell membrane, pulmonary surfactant, and lipoproteins to PM and analyzed the total burden of LPO byproducts generated as a measure of LPO index using a LPO reporter dye, BODIPY-C11. PM exposure resulted in a concentration-dependent increase in LPO. Second, we developed a novel method to expose the captured serum apoB100 lipoprotein particles to PM or its constituents and assessed the levels of specific oxidized-phospholipid on apoB100 particles by immunoassay using E06 monoclonal antibody (mab) that recognizes only PC containing oxidized-phospholipids (Ox-PCs). The immunoassay was highly sensitive to evaluate the PM LPO index and was modifiable by metal quenchers and exogenous antioxidant and radical quenchers. Third, to prove the pathophysiological relevance of Ox-PCs, we found that PM exposure generates Ox-PCs in mice lungs, pulmonary surfactant and lung cells. Fourth, we observed that treatment of macrophages with BAL fluid from PM exposed mice or PM-exposed pulmonary surfactant stimulated IL-6 production, which was abrogated by neutralization of Ox-PCs by mab E06 suggesting that Ox-PCs in lungs are proinflammatory. Overall, our study suggests that Ox-PCs as a probe of PM LPO index is a biologically relevant pathogenic biomarker and has a high value for evaluating PMOP.Sumit K. DeyKavya SugurVenkataramana G. VenkatareddyPradhi RajeevTarun GuptaRajesh K. ThimmulappaElsevierarticleParticulate matterOxidative potentialLipid peroxidationLungOxidized phospholipidsMedicine (General)R5-920Biology (General)QH301-705.5ENRedox Biology, Vol 48, Iss , Pp 102189- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Particulate matter Oxidative potential Lipid peroxidation Lung Oxidized phospholipids Medicine (General) R5-920 Biology (General) QH301-705.5
spellingShingle	Particulate matter Oxidative potential Lipid peroxidation Lung Oxidized phospholipids Medicine (General) R5-920 Biology (General) QH301-705.5 Sumit K. Dey Kavya Sugur Venkataramana G. Venkatareddy Pradhi Rajeev Tarun Gupta Rajesh K. Thimmulappa Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
description	Using particulate matter (PM) mass as exposure metric does not reveal the intrinsic PM chemical characteristics or toxic potential, which is crucial for monitoring the sources of emission causing adverse health effects and developing risk mitigating strategies. Oxidative stress and ensuing lipid peroxidation (LPO) in the lung are crucial underlying mechanisms of action by which PM drives cardiorespiratory disease. In the current study, we have postulated and demonstrated that the intrinsic potential of PM to elicit LPO, defined as “LPO index” as a novel approach for characterizing oxidative potential of PM (PMOP) and predicting biological toxicity. First, we exposed unsaturated phosphatidylcholine (PC), an abundant phospholipid in the cell membrane, pulmonary surfactant, and lipoproteins to PM and analyzed the total burden of LPO byproducts generated as a measure of LPO index using a LPO reporter dye, BODIPY-C11. PM exposure resulted in a concentration-dependent increase in LPO. Second, we developed a novel method to expose the captured serum apoB100 lipoprotein particles to PM or its constituents and assessed the levels of specific oxidized-phospholipid on apoB100 particles by immunoassay using E06 monoclonal antibody (mab) that recognizes only PC containing oxidized-phospholipids (Ox-PCs). The immunoassay was highly sensitive to evaluate the PM LPO index and was modifiable by metal quenchers and exogenous antioxidant and radical quenchers. Third, to prove the pathophysiological relevance of Ox-PCs, we found that PM exposure generates Ox-PCs in mice lungs, pulmonary surfactant and lung cells. Fourth, we observed that treatment of macrophages with BAL fluid from PM exposed mice or PM-exposed pulmonary surfactant stimulated IL-6 production, which was abrogated by neutralization of Ox-PCs by mab E06 suggesting that Ox-PCs in lungs are proinflammatory. Overall, our study suggests that Ox-PCs as a probe of PM LPO index is a biologically relevant pathogenic biomarker and has a high value for evaluating PMOP.
format	article
author	Sumit K. Dey Kavya Sugur Venkataramana G. Venkatareddy Pradhi Rajeev Tarun Gupta Rajesh K. Thimmulappa
author_facet	Sumit K. Dey Kavya Sugur Venkataramana G. Venkatareddy Pradhi Rajeev Tarun Gupta Rajesh K. Thimmulappa
author_sort	Sumit K. Dey
title	Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
title_short	Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
title_full	Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
title_fullStr	Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
title_full_unstemmed	Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
title_sort	lipid peroxidation index of particulate matter: novel metric for quantifying intrinsic oxidative potential and predicting toxic responses
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/dd0859bf5db14f17b40381050765d38e
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Lipid peroxidation index of particulate matter: Novel metric for quantifying intrinsic oxidative potential and predicting toxic responses

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