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APE1\/Ref\u20101 is an emerging therapeutic target in inflammatory conditions. This study aimed to investigate the effects of APX3330, a small molecule inhibitor of APE1's Ref\u20101 on <jats:italic>mdx<\/jats:italic> mouse pathology, a model of DMD. Six\u2010week\u2010old <jats:italic>mdx<\/jats:italic> mice and wild type (WT) C57Bl\/10 mice were treated with APX3330 (25\u2009mg\u00b7kg<jats:sup>\u22121<\/jats:sup>) or vehicle for 6\u2009weeks. Ex\u00a0vivo contractile function, histological and biochemical analysis were performed in extensor digitorum longus (EDL) and soleus muscles. APE1\/Ref\u20101 protein was greater in <jats:italic>mdx<\/jats:italic> hindlimb muscles compared to WT (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and APE1\/Ref\u20101 protein abundance was not altered by treatment with APX3330. In dystrophic EDL muscles, APX3330 treated mice had fewer (47%) infiltrating CD68\u2010positive monocytes\/macrophages (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) compared to vehicle\u2010treated <jats:italic>mdx<\/jats:italic> mice. Markers of oxidative stress, NRF2\/KEAP\u20101, were unchanged, yet phospho\u2010NF\u2010\u03baB abundance was higher with treatment (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). APX3330 treatment neither improve force output and fatiguability of isolated hindlimb muscles, nor affect muscle pathology. As APE1\/Ref\u20101 inhibition modestly lowered inflammation, with no improved contractile function, targeting solely inflammation and oxidative stress in 6\u2010week\u2010old <jats:italic>mdx<\/jats:italic> mice appears insufficient.<\/jats:p>","DOI":"10.14814\/phy2.70494","type":"journal-article","created":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T09:32:17Z","timestamp":1754040737000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["<scp>APE1<\/scp>\/Ref\u20101 inhibition via <scp>APX3330<\/scp> lowers monocyte\/macrophage infiltration without ameliorating the structure and function of dystrophic <i>mdx<\/i> hindlimb muscles"],"prefix":"10.14814","volume":"13","author":[{"given":"Hannah","family":"Lalunio","sequence":"first","affiliation":[{"name":"Department of Medicine\u2014Western Health, Melbourne Medical School The University of Melbourne  Melbourne Victoria Australia"},{"name":"Australian Institute 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Health and Sport (IHeS) Victoria University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kulmira","family":"Nurgali","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2014Western Health, Melbourne Medical School The University of Melbourne  Melbourne Victoria Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS) Victoria University  Melbourne Victoria Australia"},{"name":"Institute of Health and Sport (IHeS) Victoria University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1398-3694","authenticated-orcid":false,"given":"Alan","family":"Hayes","sequence":"additional","affiliation":[{"name":"Department of Medicine\u2014Western Health, Melbourne Medical School The University of Melbourne  Melbourne Victoria Australia"},{"name":"Australian Institute for Musculoskeletal Science (AIMSS) Victoria University  Melbourne Victoria Australia"},{"name":"Institute of Health and Sport (IHeS) Victoria University  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,8]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2015-103387"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI30556"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cdd.4401025"},{"key":"e_1_2_11_5_1","first-page":"89","article-title":"Skeletal muscle fiber types in C57BL6J mice","volume":"21","author":"Augusto V.","year":"2004","journal-title":"Journal of Morphological 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