A Brake on Toxicity: Iron Suppresses Organic-Induced Superoxide Generation in Macrophages.
5 affiliations
- 1Thrust of Sustainable Energy and Environment, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou511400, China.
- 2Department of Chemistry, University of California, Irvine, Irvine, California92697, United States.
- 3State Key Laboratory of Advanced Environmental Technology, Guangzhou Institute of Geochemistry, Chinese Academy of Sciences, Guangzhou510640, China.
- 4School of Atmospheric Sciences, Sun Yat-Sen University, Zhuhai519082, China.
- 5Thrust of Earth, Ocean and Atmospheric Sciences, The Hong Kong University of Science and Technology (Guangzhou), Guangzhou511400, China.
Abstract
Iron (Fe) is the predominant metal in brake wear particles (BWPs) and urban particulate matter, yet its role in modulating oxidative stress toxicity remains poorly understood. Here, we show that BWPs induce slight cellular superoxide (•O2-) at low doses (<10 μg mL-1) but suppress it dose-dependently at higher doses. In contrast, highway PM2.5 neither significantly induces nor suppresses cellular •O2- generation. Using Fe alone or mixed with isoprene secondary organic aerosols or 9,10-phenanthrenequinone, typical organic compounds known to induce cellular •O2- via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we demonstrate that both Fe2+ and Fe3+ actively suppress baseline and organic-induced •O2- in a dose-dependent manner. Through inhibition experiments and qRT-PCR analysis, we suggest the following mechanisms for Fe suppression on cellular •O2-: exogenous Fe replenishes the intracellular labile iron pool or complexes with organics. This alleviates organic-induced iron deficiency, reduces NADPH oxidase activity, thereby reducing •O2- release. Fe simultaneously consumes •O2- via direct chemical reactions. This work reveals iron as a suppressor rather than a promoter of organic-induced •O2- generation in macrophages, operating through restoration of iron homeostasis and direct chemical quenching. These findings underscore the importance of considering both metal and organic constituents in assessing the health impacts of complex environmental mixtures.
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BibTeX
@article{shen2026brake,
title = {{A Brake on Toxicity: Iron Suppresses Organic-Induced Superoxide Generation in Macrophages.}},
author = {Yuting Shen and Kasey C Edwards and Sukriti Kapur and Tianle Pan and Weiwei Hu and Shengzhen Zhou and Manabu Shiraiwa and Ting Fang},
journal = {Environmental science \& technology},
year = {2026},
month = sep,
doi = {10.1021/acs.est.6c06554},
url = {https://europepmc.org/article/MED/42916243},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - A Brake on Toxicity: Iron Suppresses Organic-Induced Superoxide Generation in Macrophages.
AU - Yuting Shen
AU - Kasey C Edwards
AU - Sukriti Kapur
AU - Tianle Pan
AU - Weiwei Hu
AU - Shengzhen Zhou
AU - Manabu Shiraiwa
AU - Ting Fang
PY - 2026
DA - 2026/09/01
JO - Environmental science & technology
DO - 10.1021/acs.est.6c06554
UR - https://europepmc.org/article/MED/42916243
AB - Iron (Fe) is the predominant metal in brake wear particles (BWPs) and urban particulate matter, yet its role in modulating oxidative stress toxicity remains poorly understood. Here, we show that BWPs induce slight cellular superoxide (•O2-) at low doses (<10 μg mL-1) but suppress it dose-dependently at higher doses. In contrast, highway PM2.5 neither significantly induces nor suppresses cellular •O2- generation. Using Fe alone or mixed with isoprene secondary organic aerosols or 9,10-phenanthrenequinone, typical organic compounds known to induce cellular •O2- via nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation, we demonstrate that both Fe2+ and Fe3+ actively suppress baseline and organic-induced •O2- in a dose-dependent manner. Through inhibition experiments and qRT-PCR analysis, we suggest the following mechanisms for Fe suppression on cellular •O2-: exogenous Fe replenishes the intracellular labile iron pool or complexes with organics. This alleviates organic-induced iron deficiency, reduces NADPH oxidase activity, thereby reducing •O2- release. Fe simultaneously consumes •O2- via direct chemical reactions. This work reveals iron as a suppressor rather than a promoter of organic-induced •O2- generation in macrophages, operating through restoration of iron homeostasis and direct chemical quenching. These findings underscore the importance of considering both metal and organic constituents in assessing the health impacts of complex environmental mixtures.
SN - 0013-936X
SN - 1520-5851
ER -