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Thus, this study was designed to explore the prospect of repurposing rupatadine (RUPA), a dual antagonist of histamine and platelet\u2010activating factor (PAF), against CISP\u2010evoked hepatotoxicity in rats. Rats were\n                    <jats:italic>i.p<\/jats:italic>\n                    . injected with CISP (6\u2009mg\/kg) for the induction of hepatotoxicity on the 8th day of the study in the presence and absence of RUPA in two dosages (3, 6\u2009mg\/kg) orally for 14\u2009days. Different biochemical parameters and histopathological assessments, along with the mechanistic characterizations of the possible protective impact of the RUPA were conducted. Administration of CISP evoked hepatic histopathological modifications and raised serum liver enzyme levels and hepatic MDA content, PAF, and histamine levels, along with diminishing the serum albumin level, hepatic SOD activity, and GSH level. Moreover, CISP remarkably augmented the levels of HMGB1, TLR4, p\u2010NF\u2010\u03baB p65, IL\u20106, TNF\u2010\u03b1, IL\u201018, IL\u20101\u03b2, NLRP3, and cleaved caspase\u20101 proteins with an evident decline in the level of IL\u201010. On the contrary, pretreatment with either RUPA.3 or RUPA.6 dramatically ameliorated these alterations triggered by CISP injection. RUPA counteracts hepatotoxicity evoked by CISP in rats via its anti\u2010oxidative as well as anti\u2010inflammatory properties via repression of hepatic HMGB1\/TLR4\/NF\u2010\u03baB and thus restricts the activation of NLRP3\/caspase\u20101 signaling cascade.\n                  <\/jats:p>","DOI":"10.1002\/jbt.71050","type":"journal-article","created":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T10:57:24Z","timestamp":1785409044000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rupatadine Ameliorates Cisplatin\u2010Induced Hepatotoxicity in Rats: Targeting HMGB1\/TLR4\/NF\u2010\u03baB and NLRP3\/Caspase\u20101 Signaling Pathways"],"prefix":"10.1002","volume":"40","author":[{"given":"Shaimaa Mohamed","family":"Abdelrahman","sequence":"first","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amany Abdlrehim","family":"Bekhit","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Minia University Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4469-9266","authenticated-orcid":false,"given":"Olivia N.","family":"Beshay","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy Minia University Minia Egypt"},{"name":"Department of Biochemistry, Faculty of Pharmacy Minia National University New Minia Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,30]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102925"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2014.07.025"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2026.1745023"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2024.106939"},{"key":"e_1_2_13_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-04785-z"},{"key":"e_1_2_13_7_1","doi-asserted-by":"publisher","DOI":"10.14218\/JCTH.2024.00317"},{"key":"e_1_2_13_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1223"},{"key":"e_1_2_13_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2021.174279"},{"key":"e_1_2_13_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2025.1522206"},{"key":"e_1_2_13_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2024.113006"},{"key":"e_1_2_13_12_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2021.634607"},{"key":"e_1_2_13_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10620-007-9982-2"},{"key":"e_1_2_13_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-022-18899-4"},{"key":"e_1_2_13_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/14740338.2016.1221399"},{"key":"e_1_2_13_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-020-01856-8"},{"key":"e_1_2_13_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.121710"},{"key":"e_1_2_13_18_1","doi-asserted-by":"publisher","DOI":"10.1139\/cjpp-2021-0330"},{"key":"e_1_2_13_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2024.116826"},{"key":"e_1_2_13_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10787-023-01147-7"},{"key":"e_1_2_13_21_1","doi-asserted-by":"crossref","unstructured":"X. xiLv X. xingWang K.Li et al. 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