{"id":3458,"date":"2026-07-22T01:27:31","date_gmt":"2026-07-22T01:27:31","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=3458"},"modified":"2026-07-22T01:27:31","modified_gmt":"2026-07-22T01:27:31","slug":"tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\/","title":{"rendered":"TDCPP induces ferroptosis in THP-1 macrophages through mitochondrial regulation of Fe2\u202f+ homeostasis"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone wp-image-3459\" src=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/07\/20260626-APK-300x169.jpg\" alt=\"\" width=\"850\" height=\"479\" srcset=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/07\/20260626-APK-300x169.jpg 300w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/07\/20260626-APK-1024x576.jpg 1024w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/07\/20260626-APK-768x432.jpg 768w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/07\/20260626-APK.jpg 1280w\" sizes=\"auto, (max-width: 850px) 100vw, 850px\" \/><\/p>\n<h2 class=\"section-title u-h4 u-margin-l-top u-margin-xs-bottom\">Abstract<\/h2>\n<div id=\"abs0010\">\n<div id=\"sp0035\" class=\"u-margin-s-bottom\">Widespread environmental exposure to tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a commonly used organophosphate esters, has raised significant concerns due to its structural similarity to organophosphate pesticides with known immunotoxicity. However, the immunotoxic and underlying mechanisms remain insufficiently understood. In this study, we used mRNA sequencing (mRNA-seq) to investigate the mechanisms underlying TDCPP-induced immunotoxicity following long-term low-dose exposure in THP-1 macrophages. Our findings revealed that TDCPP induces ROS generation, antioxidant depletion, iron accumulation, and lipid peroxidation lead to ferroptosis, as evidenced by lipid peroxidation and mitochondrial morphological changes observed via electron microscopy. Furthermore, TDCPP exposure led to a collapse of the cellular antioxidant defense system. The accumulation of Fe\u00b2\u207a and H\u2082O\u2082 triggered the Fenton reaction, resulting in oxidative stress and immune disorder. At the individual level, intravenous administration of TDCPP in BALB\/C mice increased serum MDA levels and decreased GSH content, significantly affecting Fe\u00b2\u207a homeostasis in lymphocytes, confirming the systemic effects of TDCPP exposure. This study is the first to demonstrate TDCPP activates ferroptosis in macrophages through mitochondrial iron imbalance and oxidative stress, resulting in lipid peroxidation in mouse blood and iron imbalance in lymphocytes, providing a theoretical basis for potential health risks in humans. There is an urgent need for further regulatory action and the development of safer alternatives.<\/div>\n<\/div>\n<div><\/div>\n<div>Full Article:\u00a0<a href=\"https:\/\/www.sciencedirect.com\/science\/article\/pii\/S014765132600761X?via%3Dihub\">https:\/\/www.sciencedirect.com\/science\/article\/pii\/S014765132600761X?via%3Dihub<\/a><\/div>\n","protected":false},"excerpt":{"rendered":"<p>Abstract Widespread environmental exposure to tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a commonly used organophosphate esters, has raised significant concerns due to its structural similarity to organophosphate pesticides with known immunotoxicity. However, the immunotoxic and underlying mechanisms remain insufficiently understood. In this study, we used mRNA sequencing (mRNA-seq) to investigate the mechanisms underlying TDCPP-induced immunotoxicity following long-term [&hellip;]<\/p>\n","protected":false},"author":9345,"featured_media":3459,"comment_status":"closed","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"site-sidebar-layout":"default","site-content-layout":"","ast-site-content-layout":"default","site-content-style":"default","site-sidebar-style":"default","ast-global-header-display":"","ast-banner-title-visibility":"","ast-main-header-display":"","ast-hfb-above-header-display":"","ast-hfb-below-header-display":"","ast-hfb-mobile-header-display":"","site-post-title":"","ast-breadcrumbs-content":"","ast-featured-img":"","footer-sml-layout":"","ast-disable-related-posts":"","theme-transparent-header-meta":"default","adv-header-id-meta":"","stick-header-meta":"default","header-above-stick-meta":"","header-main-stick-meta":"","header-below-stick-meta":"","astra-migrate-meta-layouts":"set","ast-page-background-enabled":"default","ast-page-background-meta":{"desktop":{"background-color":"var(--ast-global-color-4)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"ast-content-background-meta":{"desktop":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"tablet":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""},"mobile":{"background-color":"var(--ast-global-color-5)","background-image":"","background-repeat":"repeat","background-position":"center center","background-size":"auto","background-attachment":"scroll","background-type":"","background-media":"","overlay-type":"","overlay-color":"","overlay-opacity":"","overlay-gradient":""}},"footnotes":""},"categories":[5],"tags":[],"class_list":["post-3458","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-publications"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.0 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>TDCPP induces ferroptosis in THP-1 macrophages through mitochondrial regulation of Fe2\u202f+ homeostasis - Pharmacology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"TDCPP induces ferroptosis in THP-1 macrophages through mitochondrial regulation of Fe2\u202f+ homeostasis - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"Abstract Widespread environmental exposure to tris (1,3-dichloro-2-propyl) phosphate (TDCPP), a commonly used organophosphate esters, has raised significant concerns due to its structural similarity to organophosphate pesticides with known immunotoxicity. However, the immunotoxic and underlying mechanisms remain insufficiently understood. In this study, we used mRNA sequencing (mRNA-seq) to investigate the mechanisms underlying TDCPP-induced immunotoxicity following long-term [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\/\" \/>\n<meta property=\"og:site_name\" content=\"Pharmacology\" \/>\n<meta property=\"article:published_time\" content=\"2026-07-22T01:27:31+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/07\/20260626-APK.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"1280\" \/>\n\t<meta property=\"og:image:height\" content=\"720\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Woon Fei\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Woon Fei\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\\\/\\\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\\\/\"},\"author\":{\"name\":\"Woon Fei\",\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/#\\\/schema\\\/person\\\/ea3ccd10ab2f2bba51fd804396287cb0\"},\"headline\":\"TDCPP induces ferroptosis in THP-1 macrophages through mitochondrial regulation of Fe2\u202f+ homeostasis\",\"datePublished\":\"2026-07-22T01:27:31+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\\\/\"},\"wordCount\":237,\"publisher\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/wp-content\\\/uploads\\\/sites\\\/33\\\/2026\\\/07\\\/20260626-APK.jpg\",\"articleSection\":[\"Publications\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\\\/\",\"url\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/tdcpp-induces-ferroptosis-in-thp-1-macrophages-through-mitochondrial-regulation-of-fe2-homeostasis\\\/\",\"name\":\"TDCPP induces ferroptosis in THP-1 macrophages through mitochondrial regulation of Fe2\u202f+ homeostasis - 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