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Lipopolysaccharide (LPS) can activate diverse inflammatory pathways and has been implicated in hepatotoxicity. The store-operated calcium entry (SOCE), a key process for maintaining cellular calcium homeostasis, was shown to modulate inflammatory signaling. Reactive oxygen species, which serve a significant role in maintaining cellular function and homeostasis, are often elevated during inflammation, contributing to tissue injury. Therefore, we hypothesized that blocking the SOCE pathway would inhibit LPS-induced hepatotoxicity by suppressing inflammation and oxidative stress.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>To test this, female BALB\/c mice were randomly divided into the following experimental groups: control, LPS, LPS + SOCE inhibitor 2-aminoethoxy diphenyl borate (2APB), and 2APB alone. After 24\u00a0h of treatment, serum and liver samples were collected from the mice for histopathological, biochemical, and molecular analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Inhibition of SOCE led to a decrease in the elevated liver function enzymes (ALT and AST) and protected the liver parenchymal cells as observed by histopathological assessment. Furthermore, blockade of SOCE significantly suppressed the level of\n                      <jats:italic toggle=\"yes\">il-1b<\/jats:italic>\n                      ,\n                      <jats:italic toggle=\"yes\">il-6<\/jats:italic>\n                      , and\n                      <jats:italic toggle=\"yes\">cox2<\/jats:italic>\n                      genes in the liver tissues of mice treated with LPS. The expression of antioxidant genes (\n                      <jats:italic toggle=\"yes\">gsta1<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">gpx1<\/jats:italic>\n                      ) was also significantly reduced by LPS treatment, while SOCE inhibition only restored the\n                      <jats:italic toggle=\"yes\">gpx1<\/jats:italic>\n                      expression. Additionally, treatment with 2APB attenuated LPS-induced oxidative stress in the liver of mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Collectively, our work demonstrated the critical involvement of SOCE in regulating inflammation and oxidative stress associated with LPS treatment, thereby reducing hepatotoxicity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251411659","type":"journal-article","created":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T06:57:57Z","timestamp":1767941877000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Inhibition of store-operated calcium entry mitigates lipopolysaccharide-induced hepatotoxicity via modulating inflammatory and oxidative stress responses"],"prefix":"10.1177","volume":"45","author":[{"given":"Mohammed","family":"Alqinyah","sequence":"first","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8933-3490","authenticated-orcid":false,"given":"Abdullah S.","family":"Alhamed","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasseen A.","family":"Alassmrry","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed","family":"Mohany","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6690-3155","authenticated-orcid":false,"given":"Khaldoon","family":"Aljerian","sequence":"additional","affiliation":[{"name":"University of Alberta, Edmonton, Canada"},{"name":"University of Alberta, Edmonton, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1890-1291","authenticated-orcid":false,"given":"Khalid","family":"Alhazzani","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohammad M.","family":"Algahtani","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hussain N.","family":"Alhamami","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2937-540X","authenticated-orcid":false,"given":"Ahmed Z.","family":"Alanazi","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Faris","family":"Almutairi","sequence":"additional","affiliation":[{"name":"King Saud University"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2026,1,8]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1080\/10937404.2023.2261848"},{"key":"e_1_3_6_3_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.32689"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.23208"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21217894"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2010.183"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.3904\/kjim.2010.25.4.364"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1186\/s40164-024-00527-1"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00281-022-00910-2"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cyto.2008.01.006"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.3390\/vaccines5040034"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.01.011"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1186\/1755-1536-3-21"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41401-020-00597-x"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","unstructured":"Biswas SK. 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