{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T05:06:18Z","timestamp":1790139978228,"version":"4.0.1"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Diquat (DQ), a widely used bipyridyl herbicide, induces acute liver injury primarily through oxidative stress, and effective targeted therapies remain lacking.\n                      <jats:italic>Lactobacillus rhamnosus<\/jats:italic>\n                      GG (LGG) exhibits antioxidant potential, but its role in DQ-induced liver injury has not been fully clarified. This study investigated the protective effects of LGG and its associated metabolite 5-methoxyindole-3-acetic acid (5-MIAA) and explored the underlying mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A DQ-induced acute liver injury model was established in C57BL\/6 mice with LGG pretreatment and Nrf2 inhibitor (ML385) intervention. Liver function, histopathology, oxidative stress markers, and Nrf2\/HO-1 expression were assessed.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , DQ-treated HepG2 cells were exposed to varying concentrations of 5-MIAA, and cell viability and pathway-related molecules were analyzed using CCK-8 and Western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      DQ exposure markedly elevated ALT and AST levels, aggravated hepatic necrosis and inflammation, increased ROS and MDA levels, decreased SOD and GSH-Px activities, and suppressed Nrf2 and HO-1 expression. LGG pretreatment significantly alleviated liver injury and oxidative stress while restoring Nrf2\/HO-1 expression. ML385 partially attenuated the protective effects of LGG.\n                      <jats:italic>In vitro<\/jats:italic>\n                      , 5-MIAA dose-dependently improved viability of DQ-injured HepG2 cells and upregulated Nrf2 and HO-1 expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>LGG mitigates DQ-induced acute liver injury by activating the Nrf2\/HO-1 pathway and reducing oxidative stress, while 5-MIAA may represent a potential bioactive compound with similar hepatoprotective effects. These findings provide mechanistic support for probiotic-based strategies in toxicant-induced liver injury.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1904443","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T04:45:24Z","timestamp":1790138724000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Protective effects of Lactobacillus rhamnosus GG and 5-methoxyindole-3-acetic acid against diquat-induced acute liver injury involve activation of the Nrf2\/HO-1 signaling pathway"],"prefix":"10.3389","volume":"17","author":[{"given":"Yu","family":"Wang","sequence":"first","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenbin","family":"Gao","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yonghong","family":"Wang","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxuan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiahao","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Physiology, Mcgill University","place":["Montreal, QC, Canada"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Li","sequence":"additional","affiliation":[{"name":"Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Tongji Shanxi Hospital","place":["Taiyuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1289\/ehp.85-1568326","article-title":"An assessment of the role of redox cycling in mediating the toxicity of paraquat and nitrofurantoin","volume":"85","author":"Adam","year":"1990","journal-title":"Environ. 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