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Glucuronolactone (GLU) has been shown to be a potent antioxidant that helps alleviate oxidative stress. Therefore, this study aimed to investigate the effect of GLU on oxidative stress and lung injury induced by co-challenge with PRRSV and DON. Eighteen weaned piglets were randomly divided into three groups: control (CON), DON, and DON\u2009+\u2009GLU. After DON and\/or GLU treatment for two weeks, all pigs were intramuscularly injected with PRRSV and treated with DON and\/or GLU for another three weeks. Three weeks post-PRRSV infection, piglets in the DON group exhibited impaired growth performance, severe lung injury, and elevated viral loads. By contrast, piglets in the DON\u2009+\u2009GLU group showed improved growth performance and lung health, as well as reduced viral loads. GLU also inhibited inflammation, excessive autophagy and apoptosis induced by PRRSV and DON co-challenge in both porcine lung and MARC-145 cells, as indicated by reduced expression of pro-inflammatory factors, autophagy marker LC3, and apoptosis-related markers. Importantly, GLU can promote the phosphorylation and nuclear import of Nrf2, thereby enhancing antioxidant capacity and alleviating oxidative stress induced by PRRSV and DON co-challenge. Nrf2 inhibitor ML385 abolished the protective effect of GLU on inflammation and oxidative stress triggered by PRRSV and DON co-challenge. These findings suggest that GLU could mitigate oxidative stress to alleviate lung injury induced by PRRSV and DON co-challenge via activating the Nrf2 pathway, highlighting its potential as a dietary supplement in the pig industry.<\/jats:p>","DOI":"10.1186\/s13567-025-01596-8","type":"journal-article","created":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T15:06:39Z","timestamp":1754406399000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Glucuronolactone improves lung injury caused by PRRSV and DON co-challenge by enhancing the Nrf2-mediated antioxidant capacity in weaning piglets"],"prefix":"10.1186","volume":"56","author":[{"given":"Jing","family":"Hou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenbin","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Wu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shilong","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guohao","family":"Ye","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaoyang","family":"Tian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiaxi","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaiguo","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zongyong","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yueqin","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3144-2939","authenticated-orcid":false,"given":"Xuefen","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"1596_CR1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.3390\/toxins10030113","volume":"10","author":"R Ma","year":"2018","unstructured":"Ma R, Zhang L, Liu M, Su Y, Xie W, Zhang N, Dai J, Wang Y, Rajput SA, Qi D, Karrow NA, Sun LH (2018) Individual and combined occurrence of mycotoxins in feed ingredients and complete feeds in China. 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