{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:36:30Z","timestamp":1776677790805,"version":"3.51.2"},"reference-count":56,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T00:00:00Z","timestamp":1776643200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Offspring of preeclamptic (PE) mothers are at increased risk of end-organ damage. Given the widespread use of NSAIDs during pregnancy and their reported ability to mitigate organ damage in PE mothers, this study examined whether prenatal naproxen modifies PE-induced lung injury in male and female offspring. PE was induced by orally administered L-nitro-arginine-methyl ester (L-NAME, 50 mg\/kg\/day for 7 days) to mothers prior to labor, and lung tissues were excised from 3-month-old offspring. Histopathology revealed increased interstitial inflammation and fibrosis in PE versus non-PE offspring lungs. This was more prominent in male than in female PE offspring and was coupled with more pulmonary expression of Axl tyrosine kinase receptor and downstream interleukin-1\u03b1 (IL-1\u03b1) and antiangiogenic Fms-Like Tyrosine Kinase-1(sFlt1) effectors. These sex-related defects disappeared in offspring of PE dams treated prenatally with naproxen (1 mg\/kg\/day for 7 days). Further, PE offspring exhibited elevations in other inflammatory cytokines, IL-2 and TNF\u03b1, and apoptotic markers, caspase-3 and caspase-cleaved cytokeratin 18 (M-30) and total soluble cytokeratin 18 (M-65). The latter effects were evenly seen in both sexes and similarly offset by naproxen. These findings implicate Axl\/IL-1\u03b1\/sFlt1 signaling in the greater lung injury in male PE offspring and suggest a protective effect of gestational naproxen therapy.<\/jats:p>","DOI":"10.3390\/ijms27083653","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T08:24:23Z","timestamp":1776673463000},"page":"3653","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Naproxen Reprograms Histopathological and Molecular Facets of the Sex-Based Lung Injury in Adult Offspring of Preeclamptic Rats"],"prefix":"10.3390","volume":"27","author":[{"given":"Sherien A.","family":"Abdelhady","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Biochemistry, Faculty of Pharmacy, Horus University in Egypt, New Damietta 21521, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5289-1488","authenticated-orcid":false,"given":"Reem H.","family":"Elhamammy","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Pharmacy, Alexandria University, Alexandria 21526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohamed H.","family":"Noureldin","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Division of Clinical and Biological Sciences, College of Pharmacy, Arab Academy for Science, Technology and Maritime Transport, Alexandria 21625, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasmine","family":"Shahine","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, Pharos University in Alexandria, Alexandria 21526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nevine M.","family":"El-Deeb","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Alexandria University, Alexandria 21526, Egypt"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahmoud M.","family":"El-Mas","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Alexandria 21526, Egypt"},{"name":"Department of Pharmacology and Toxicology, College of Medicine, Kuwait University, Shadadiya 13060, Kuwait"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1042\/CS20150702","article-title":"The role of inflammation in the pathology of preeclampsia","volume":"130","author":"Harmon","year":"2016","journal-title":"Clin. 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