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In this study, we aimed to evaluate the effects of astaxanthin on oxidative stress, inflammation, and mitochondrial health in peripheral blood mononuclear cells (PBMC) isolated from Arabian racehorses. Horse-derived peripheral blood mononuclear cells exposed to hydrogen peroxide (H\u2082O\u2082) presented increased reactive oxygen species (ROS) accumulation and overexpression of pro-inflammatory cytokines such as IL-1\u03b2, IL-6, IFN-\u03b3, and TNF-\u03b1. The addition of astaxanthin to cell culture reduced H\u2082O\u2082-induced inflammatory response by decreasing the expression levels of all the tested pro-inflammatory cytokines. Moreover, astaxanthin displayed a potential antioxidant response by increasing the expression of genes related to antioxidative defense, such as <jats:italic>NRF1<\/jats:italic>, <jats:italic>SOD2<\/jats:italic>, and <jats:italic>GPX<\/jats:italic>. Interestingly, PBMCs isolated from the horses orally supplemented with astaxanthin increased the expression of the mitophagy-related genes <jats:italic>PINK1<\/jats:italic> and <jats:italic>PARKIN<\/jats:italic>. Moreover, genes related to mitochondrial dynamics and energy production, such as <jats:italic>PPARGC1B<\/jats:italic>,<jats:italic> NDUFA9<\/jats:italic>, and <jats:italic>MRPL24<\/jats:italic>, as well as genes associated with mitochondrial function, structure and dynamics, such as <jats:italic>PIGBOS<\/jats:italic>,<jats:italic> MRLP24<\/jats:italic>,<jats:italic> PUSL1<\/jats:italic> and <jats:italic>TFAM<\/jats:italic> were upregulated in PBMCs isolated from astaxanthin supplemented horses. Altogether, these findings indicate that astaxanthin may be a beneficial dietary supplement for equine health, supporting resilience against oxidative stress and inflammatory challenges, and improving the recovery and performance of racing horses.<\/jats:p>","DOI":"10.1038\/s41598-025-93661-7","type":"journal-article","created":{"date-parts":[[2025,4,26]],"date-time":"2025-04-26T07:03:02Z","timestamp":1745650982000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Astaxanthin supplementation in Arabian racing horses mitigates oxidative stress and inflammation in peripheral blood mononuclear cells through enhanced mitophagy"],"prefix":"10.1038","volume":"15","author":[{"given":"Beata","family":"Giercuszkiewicz-Hecold","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Pajuelo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zofia","family":"Steczkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cywinska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krzysztof","family":"Marycz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,4,26]]},"reference":[{"key":"93661_CR1","first-page":"7167","volume":"27","author":"G Bj\u00f8rklund","year":"2022","unstructured":"Bj\u00f8rklund, G. et al. 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