{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T04:20:11Z","timestamp":1787977211333,"version":"build-2784847793"},"reference-count":63,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T00:00:00Z","timestamp":1758758400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["42177416"],"award-info":[{"award-number":["42177416"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["42477452"],"award-info":[{"award-number":["42477452"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Scientific Research Innovative Team of Hubei University of Science and Technology","award":["2023T08"],"award-info":[{"award-number":["2023T08"]}]},{"name":"Key Special Project for Social Development R&D of Xianning City Science and Technology Program","award":["2023SFYF095"],"award-info":[{"award-number":["2023SFYF095"]}]},{"name":"Joint supported by Hubei Provincial Natural Science Foundation and Xianning of China","award":["2025AFD389"],"award-info":[{"award-number":["2025AFD389"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Background: Dibutyl phthalate (DBP) is a prevalent environmental pollutant that can accumulate in organisms, becoming amplified after the food cycle and ultimately affecting human health. Recent studies have provided evidence suggesting a potential association between exposure to DBP and cardiovascular diseases (CVDs). Objectives: This study\u2019s objective is to investigate the toxic cardiovascular effects of long-term exposure to DBP, particularly its impact on the heart and blood vessels. To be specific, we hypothesized and verified the potential mechanisms underlying DBP-induced cardiac and vascular injuries, focusing on oxidative stress, pyroptosis, inflammatory responses, and metabolic pathways. Methods: The rats were divided into 5 groups: Control group, DBP-Low group, DBP-Medium group, DBP-High group, and DBP-High + Vitamin E group. The entire experimental period lasted 12 weeks. We conducted examinations on echocardiography, histopathology, oxidative stress biomarkers, pyroptosis-related biomarkers, and inflammatory cytokine biomarkers. Additionally, we carried out serum metabolomics analysis. Result: Our research findings indicate that long-term exposure to DBP can cause significant toxic effects on the cardiovascular system. Specifically, DBP leads to changes in oxidative stress indicators (ROS and an increase in MDA levels, alongside a decrease in GSH levels) and protein levels related to pyroptosis (NLRP3, Caspase-1 and GSDMD levels increase) in cardiac and vascular tissues, triggering oxidative inflammatory responses (IL-1\u03b2 and IL-18 levels increase), damaging the heart and blood vessels (organizational structure deformation and collagen fiber infiltration) and ultimately affecting their functions (abnormalities in cardiac function and hemodynamics). Additionally, the results of metabolomics studies suggest that metabolic pathways (Biotin metabolism, TCA cycle, Vitamin B6 metabolism, Pantothenate and CoA biosynthesis, and Riboflavin metabolism) and metabolites may also be of great significance. Conclusion: Long-term exposure to DBP can induce cardiovascular toxicity in rats, manifesting as cardiac and vascular damage, as well as alterations in organ function. This process is characterized by oxidative stress, activation of the pyroptosis pathway, inflammatory responses, and modifications to metabolic pathways.<\/jats:p>","DOI":"10.3390\/toxics13100815","type":"journal-article","created":{"date-parts":[[2025,9,25]],"date-time":"2025-09-25T13:48:05Z","timestamp":1758808085000},"page":"815","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Probing the Cardiovascular Toxic Effects of Long-Term Exposure to Dibutyl Phthalate in Sprague-Dawley Rats Based on Oxidative Inflammation and Metabolic Pathways: Implications for the Heart and Blood Vessel"],"prefix":"10.3390","volume":"13","author":[{"given":"Xiao","family":"Liang","sequence":"first","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"School of Public Health and Nursing, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Huang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"School of Public Health and Nursing, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Wu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deyu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhuangzhuang","family":"Wei","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"Centre for Biological Science and Technology, Key Laboratory of Cell Proliferation and Regulation Biology of Ministry of Education, Faculty of Arts and Sciences, Beijing Normal University, Zhuhai 519000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Ma","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8015-6299","authenticated-orcid":false,"given":"Xu","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"Institute of Natural Antioxidants and Antioxidant Inflammation, Dali University, Dali 671003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiyu","family":"Bao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Bao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environmental Related Diseases and One Health, Xianning Medical College, Hubei University of Science and Technology, Xianning 437100, China"},{"name":"School of Public Health and Nursing, Hubei University of Science and Technology, Xianning 437100, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"134920","DOI":"10.1016\/j.jhazmat.2024.134920","article-title":"Microplastics emerge as a hotspot for dibutyl phthalate sources in rivers and oceans: Leaching behavior and potential risks","volume":"475","author":"Lin","year":"2024","journal-title":"J. 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