J Environ Sci (China). 2026 Aug;166:785-798. doi: 10.1016/j.jes.2025.11.007. Epub 2025 Nov 7.
ABSTRACT
Di(2-ethylhexyl) phthalate (DEHP), a widely used plasticizer, impairs cardiac development and increases the risk of cardiovascular disease. Astaxanthin (ASX), a natural carotenoid, has recognized cardiovascular benefits, but its protective effects against DEHP-induced cardiac injury and underlying mechanisms remain unclear. Using transcriptomic data, bioinformatic analysis identified signaling pathways associated with DEHP-induced cardiac injury. Network pharmacology integrated with machine learning predicted potential ASX targets. The cardioprotective effects of ASX were validated in C57BL/6 mice and H9c2 cells to explore mechanisms in vivo and in vitro. Bioinformatic analysis revealed autophagy as a central pathway in DEHP cardiotoxicity, with PPAR-α identified as a hub gene regulating autophagy. Experimental results showed that ASX significantly alleviated DEHP-induced cardiac injury, demonstrated by improved histopathology, reduced myocardial enzyme levels, and decreased oxidative stress. Western blotting confirmed that ASX reduced the expression of PPAR-α, Beclin 1, and LC3, whereas increasing p62 expression in DEHP-exposed mice and MEHP-treated H9c2 cells. These findings demonstrate that ASX mitigates DEHP-induced cardiac injury by suppressing autophagy through selective inhibition of PPAR-α. ASX supplementation may represent a promising dietary strategy to counteract cardiovascular toxicity from environmental pollutants.
PMID:42336584 | DOI:10.1016/j.jes.2025.11.007