{"id":3560,"date":"2026-09-08T06:22:09","date_gmt":"2026-09-08T06:22:09","guid":{"rendered":"https:\/\/medicine.nus.edu.sg\/medphc\/?p=3560"},"modified":"2026-09-08T06:22:09","modified_gmt":"2026-09-08T06:22:09","slug":"spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway","status":"publish","type":"post","link":"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\/","title":{"rendered":"Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1\u2013dependent antioxidant pathway"},"content":{"rendered":"<p><img loading=\"lazy\" decoding=\"async\" class=\"alignnone  wp-image-3561\" src=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/09\/20260411-GS-300x169.jpg\" alt=\"\" width=\"850\" height=\"479\" srcset=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/09\/20260411-GS-300x169.jpg 300w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/09\/20260411-GS-1024x576.jpg 1024w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/09\/20260411-GS-768x432.jpg 768w, https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/09\/20260411-GS.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=\"abss0002\" class=\"abstract author\">\n<h3 id=\"cesectitle0003\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\"><em><span style=\"font-size: 14pt;\">Background<\/span><\/em><\/h3>\n<div id=\"spara011\" class=\"u-margin-s-bottom\">Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy.<\/div>\n<\/div>\n<div id=\"abss0003\" class=\"abstract author\">\n<h3 id=\"cesectitle0004\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\"><em><span style=\"font-size: 14pt;\">Purpose<\/span><\/em><\/h3>\n<div id=\"spara012\" class=\"u-margin-s-bottom\">To determine the therapeutic potential and mechanistic basis of SPD in septic cardiac dysfunction.<\/div>\n<\/div>\n<div id=\"abss0004\" class=\"abstract author\">\n<h3 id=\"cesectitle0005\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\"><em><span style=\"font-size: 14pt;\">Methods<\/span><\/em><\/h3>\n<div id=\"spara013\" class=\"u-margin-s-bottom\">Network pharmacology, RNA sequencing, a cecal ligation and puncture (CLP) mouse model, and multiple cellular assays were integrated to assess the protective actions of SPD. Mitochondrial function, mitophagy flux, and oxidative stress were evaluated using transmission electron microscopy (TEM), immunohistochemistry (IHC), Western blotting, structured illumination microscopy (SIM), mitochondrial membrane potential assays, oxygen consumption rate (OCR) analysis, and mitochondrial DNA (mtDNA) quantification. Transcriptomic clustering and pathway enrichment identified molecular targets, which were validated through siRNA-mediated gene silencing.<\/div>\n<\/div>\n<div id=\"abss0005\" class=\"abstract author\">\n<h3 id=\"cesectitle0006\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\"><em><span style=\"font-size: 14pt;\">Results<\/span><\/em><\/h3>\n<div id=\"spara014\" class=\"u-margin-s-bottom\">SPD markedly attenuated SICM <em>in vivo<\/em> and <em>in vitro<\/em> by improving both mitochondrial quantity and quality. It restored sepsis-impaired mitophagy by upregulating LC3B and ATG7, promoting autophagosome maturation, and enhancing cellular ubiquitination. Transcriptomic profiling highlighted metallothionein-1 (MT1) as a key node in metal-ion response pathways. SPD activated the NRF2\u2013MT1\u2013SOD2 antioxidant axis, reduced mitochondrial reactive oxygen species (mtROS) under lipopolysaccharide (LPS) stimulation, and reversed sepsis-induced suppression of SOD2. MT1 knockdown abolished SPD-mediated SOD2 stabilization and mtROS clearance, confirming its essential role in SPD\u2019s cardioprotective effects.<\/div>\n<\/div>\n<div id=\"abss0006\" class=\"abstract author\">\n<h3 id=\"cesectitle0007\" class=\"u-h4 u-margin-m-top u-margin-xs-bottom\"><em><span style=\"font-size: 14pt;\">Conclusion<\/span><\/em><\/h3>\n<div id=\"spara015\" class=\"u-margin-s-bottom\">SPD mitigates SICM by orchestrating the restoration of mitochondrial quality control, normalization of mitophagic flux, and stabilization of cellular redox homeostasis. These findings support SPD as a promising therapeutic candidate for septic cardiomyopathy.<\/div>\n<\/div>\n<div><\/div>\n<div>Full Article: https:\/\/www.sciencedirect.com\/science\/article\/abs\/pii\/S0944711326004083?via%3Dihub<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Abstract Background Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy. Purpose To determine the therapeutic potential and mechanistic basis [&hellip;]<\/p>\n","protected":false},"author":9345,"featured_media":3561,"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-3560","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>Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1\u2013dependent antioxidant pathway - 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\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1\u2013dependent antioxidant pathway - Pharmacology\" \/>\n<meta property=\"og:description\" content=\"Abstract Background Sepsis-induced cardiomyopathy (SICM) is characterized by mitochondrial dysfunction, impaired mitophagic flux, and overwhelming oxidative stress. 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Purpose To determine the therapeutic potential and mechanistic basis [&hellip;]\" \/>\n<meta property=\"og:url\" content=\"https:\/\/medicine.nus.edu.sg\/medphc\/publications\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\/\" \/>\n<meta property=\"og:site_name\" content=\"Pharmacology\" \/>\n<meta property=\"article:published_time\" content=\"2026-09-08T06:22:09+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/medicine.nus.edu.sg\/medphc\/wp-content\/uploads\/sites\/33\/2026\/09\/20260411-GS.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\\\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\\\/#article\",\"isPartOf\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\\\/\"},\"author\":{\"name\":\"Woon Fei\",\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/#\\\/schema\\\/person\\\/ea3ccd10ab2f2bba51fd804396287cb0\"},\"headline\":\"Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1\u2013dependent antioxidant pathway\",\"datePublished\":\"2026-09-08T06:22:09+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\\\/\"},\"wordCount\":290,\"publisher\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/#organization\"},\"image\":{\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\\\/#primaryimage\"},\"thumbnailUrl\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/wp-content\\\/uploads\\\/sites\\\/33\\\/2026\\\/09\\\/20260411-GS.jpg\",\"articleSection\":[\"Publications\"],\"inLanguage\":\"en-US\"},{\"@type\":\"WebPage\",\"@id\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\\\/\",\"url\":\"https:\\\/\\\/medicine.nus.edu.sg\\\/medphc\\\/publications\\\/spermidine-alleviates-sepsis-induced-cardiomyopathy-by-improving-mitochondrial-quality-and-quantity-via-a-metallothionein-1-dependent-antioxidant-pathway\\\/\",\"name\":\"Spermidine alleviates sepsis-induced cardiomyopathy by improving mitochondrial quality and quantity via a Metallothionein 1\u2013dependent antioxidant pathway - 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Spermidine (SPD), a natural polyamine known to enhance autophagy and preserve cardiac function in aging and metabolic disorders, has not been systematically evaluated in the context of septic cardiomyopathy. 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