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It showed anti-inflammatory, neuroprotective, and antioxidant activity in many experimental studies. This study was aimed at exploring the hepatoprotective potential of secukinumab against diethylnitrosamine (DEN)-induced acute liver injury in mice, with an emphasis on its anti-inflammatory, antioxidant, and antipyroptotic properties. Thirty-six male mice were randomly divided into six groups\u2014group one (Control): mice did not receive any treatment; group two (SEC20): mice received SEC (20\u00a0mg\/kg, i.p.) only; group three (DEN group): mice received DEN (150\u00a0mg\/kg, i.p.); group four (SEC5\u2009+\u2009DEN): mice received SEC (5\u00a0mg\/kg, i.p.) then injected with DEN 1\u00a0h after SEC administration; group five (SEC10\u2009+\u2009DEN): mice received SEC (10\u00a0mg\/kg, i.p.), then injected with DEN 1\u00a0h after SEC administration; and group six (SEC20\u2009+\u2009DEN): mice received SEC (20\u00a0mg\/kg, i.p.) then injected with DEN 1\u00a0h after SEC administration. Compared to DEN-injected mice, secukinumab at the dose of 5, 10, and 20\u00a0mg\/kg significantly decreased serum levels of ALT, AST, GGT, and LDH as well as hepatic levels of MDA, IL-17A, p-ERK, p-eIF2\u03b1, CHOP, NLRP3, and IL-1\u03b2, in addition to increased serum level of albumin as well as hepatic levels of GSH and TAC. Histopathologically, secukinumab attenuated DEN-induced histopathological irregularities in hepatic tissues. Moreover, secukinumab markedly reduced the hepatic expression of NF-\u03baB and Caspase-1. Secukinumab at the doses (5, 10, and 20\u00a0mg) showed hepatoprotective, antioxidant, and anti-inflammatory effects against DEN-induced hepatotoxicity in mice.<\/jats:p>","DOI":"10.1007\/s00210-026-05142-x","type":"journal-article","created":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T02:49:26Z","timestamp":1774579766000},"page":"13513-13526","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Secukinumab mitigates diethyl nitrosamine-induced acute liver injury in mice via modulating p-ERK\/p-eIF2\u03b1\/CHOP and NLRP3\/Caspase-1\/IL-1\u03b2 pathways"],"prefix":"10.1007","volume":"399","author":[{"given":"Zaid F.","family":"AL-rasheedi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omnia A.","family":"Nour","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dalia H.","family":"El-Kashef","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,27]]},"reference":[{"key":"5142_CR1","doi-asserted-by":"publisher","first-page":"3291","DOI":"10.1007\/s12035-020-01972-9","volume":"57","author":"AE-S Abdel-Maged","year":"2020","unstructured":"Abdel-Maged AE-S, Gad AM, Rashed LA, Azab SS, Mohamed EA, Awad AS (2020) Repurposing of secukinumab as neuroprotective in cuprizone-induced multiple sclerosis experimental model via inhibition of oxidative, inflammatory, and neurodegenerative signaling. 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