{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T17:48:18Z","timestamp":1769881698204,"version":"3.49.0"},"reference-count":41,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Life Sciences"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.lfs.2025.123634","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T11:53:23Z","timestamp":1744631603000},"page":"123634","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":2,"special_numbering":"C","title":["Roflumilast counteracts high-dose dexamethasone-induced steatohepatitis, metabolic abnormalities and aortic injury via inhibiting TNF-\u03b1\/NF-\u03baB, NLRP3\/IL-1\u03b2 and ER stress sensors"],"prefix":"10.1016","volume":"372","author":[{"given":"Mohammed Fulayyih","family":"Aloufi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sara H.","family":"Hazem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rania R.","family":"Abdelaziz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghada M.","family":"Suddek","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.lfs.2025.123634_bb0005","doi-asserted-by":"crossref","first-page":"1048","DOI":"10.3389\/fphar.2018.01048","article-title":"Phosphodiesterase-4 inhibitors for the treatment of inflammatory diseases","volume":"9","author":"Li","year":"2018","journal-title":"Front. Pharmacol."},{"issue":"9","key":"10.1016\/j.lfs.2025.123634_bb0010","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1038\/labinvest.2017.59","article-title":"Roflumilast reverses polymicrobial sepsis-induced liver damage by inhibiting inflammation in mice","volume":"97","author":"Feng","year":"2017","journal-title":"Lab. Investig."},{"issue":"1","key":"10.1016\/j.lfs.2025.123634_bb0015","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1172\/JCI41681","article-title":"LXR\u03b2 is required for glucocorticoid-induced hyperglycemia and hepatosteatosis in mice","volume":"121","author":"Patel","year":"2011","journal-title":"J. Clin. Invest."},{"key":"10.1016\/j.lfs.2025.123634_bb0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.intimp.2024.112323","article-title":"The hidden dangers of short-term glucocorticoid use in children: a genomic analysis","volume":"135","author":"Xu","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"10.1016\/j.lfs.2025.123634_bb0025","doi-asserted-by":"crossref","DOI":"10.1016\/j.taap.2023.116774","article-title":"Saroglitazar mitigated NASH-associated hepatic injury in dexamethasone-treated rats via modulating autophagy, apoptosis, and necroptosis","volume":"482","author":"Amer","year":"2024","journal-title":"Toxicol. Appl. Pharmacol."},{"issue":"2","key":"10.1016\/j.lfs.2025.123634_bb0030","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1002\/dmrr.2486","article-title":"Steroid-induced diabetes: a clinical and molecular approach to understanding and treatment","volume":"30","author":"Hwang","year":"2014","journal-title":"Diabetes Metab. Res. Rev."},{"issue":"3","key":"10.1016\/j.lfs.2025.123634_bb0035","article-title":"Effectiveness of Roflumilast in treating chronic obstructive pulmonary disease: a systematic review and Meta-analysis","volume":"14","author":"Naseem","year":"2022","journal-title":"Cureus"},{"key":"10.1016\/j.lfs.2025.123634_bb0040","first-page":"147","article-title":"Roflumilast: first phosphodiesterase 4 inhibitor approved for treatment of COPD","volume":"4","author":"Giembycz","year":"2010","journal-title":"Drug Des. Devel. Ther."},{"issue":"4","key":"10.1016\/j.lfs.2025.123634_bb0045","doi-asserted-by":"crossref","first-page":"299","DOI":"10.4046\/trd.2018.0015","article-title":"Incidence of adverse effects and discontinuation rate between patients receiving 250 micrograms and 500 micrograms of Roflumilast: a comparative study","volume":"81","author":"Joo","year":"2018","journal-title":"Tuberc Respir Dis (Seoul)."},{"issue":"4","key":"10.1016\/j.lfs.2025.123634_bb0050","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1007\/s10753-017-0567-8","article-title":"Roflumilast reduces cerebral inflammation in a rat model of experimental subarachnoid hemorrhage","volume":"40","author":"Wu","year":"2017","journal-title":"Inflammation"},{"issue":"6","key":"10.1016\/j.lfs.2025.123634_bb0055","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1097\/FBP.0000000000000640","article-title":"Positive effects of roflumilast on behavior, neuroinflammation, and white matter injury in mice with global cerebral ischemia","volume":"32","author":"Vilhena","year":"2021","journal-title":"Behav. Pharmacol."},{"issue":"6","key":"10.1016\/j.lfs.2025.123634_bb0060","doi-asserted-by":"crossref","first-page":"302","DOI":"10.3892\/etm.2023.12001","article-title":"Roflumilast reduces myocardial ischemia reperfusion injury in vivo and in vitro by activating the AMPK signaling pathway","volume":"25","author":"Liao","year":"2023","journal-title":"Exp. Ther. Med."},{"issue":"Pt B","key":"10.1016\/j.lfs.2025.123634_bb0065","article-title":"Roflumilast extenuates inflammation and oxidative stress in cadmium-induced hepatic and testicular injury in rats","volume":"124","author":"Sulayman Aboulqassim","year":"2023","journal-title":"Int. Immunopharmacol."},{"issue":"3","key":"10.1016\/j.lfs.2025.123634_bb0070","doi-asserted-by":"crossref","DOI":"10.1002\/prp2.791","article-title":"Dexamethasone promotes the endoplasmic reticulum stress response of bone marrow mesenchymal stem cells by activating the PERK-Nrf2 signaling pathway","volume":"9","author":"Cheng","year":"2021","journal-title":"Pharmacol. Res. Perspect."},{"key":"10.1016\/j.lfs.2025.123634_bb0075","doi-asserted-by":"crossref","DOI":"10.1016\/j.jep.2022.115154","article-title":"Geniposide ameliorated dexamethasone-induced endoplasmic reticulum stress and mitochondrial apoptosis in osteoblasts","volume":"291","author":"Xiao","year":"2022","journal-title":"J. Ethnopharmacol."},{"issue":"1","key":"10.1016\/j.lfs.2025.123634_bb0080","doi-asserted-by":"crossref","first-page":"81","DOI":"10.3171\/jns.1986.64.1.0081","article-title":"Effect of high-dose dexamethasone on outcome from severe head injury","volume":"64","author":"Dearden","year":"1986","journal-title":"J. Neurosurg."},{"issue":"9","key":"10.1016\/j.lfs.2025.123634_bb0085","doi-asserted-by":"crossref","first-page":"831","DOI":"10.1056\/NEJMoa030254","article-title":"Initial treatment of immune thrombocytopenic purpura with high-dose dexamethasone","volume":"349","author":"Cheng","year":"2003","journal-title":"N. Engl. J. Med."},{"issue":"7","key":"10.1016\/j.lfs.2025.123634_bb0090","doi-asserted-by":"crossref","first-page":"1913","DOI":"10.1007\/s11739-021-02800-1","article-title":"High-dose dexamethasone treatment for COVID-19 severe acute respiratory distress syndrome: a retrospective study","volume":"16","author":"Vecchi\u00e9","year":"2021","journal-title":"Intern. Emerg. Med."},{"key":"10.1016\/j.lfs.2025.123634_bb0095","article-title":"Dose dependent hepatic and endothelial changes in rats treated with dexamethasone","volume":"9(5):Ff08-10","author":"Kumar","year":"2015","journal-title":"J. Clin. Diagn. Res."},{"issue":"1","key":"10.1016\/j.lfs.2025.123634_bb0100","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1186\/s43088-019-0021-0","article-title":"Thymus vulgaris extract modulates dexamethasone induced liver injury and restores the hepatic antioxidant redox system","volume":"8","author":"Abou-Seif","year":"2019","journal-title":"Beni-Suef University Journal of Basic and Applied Sciences."},{"issue":"1","key":"10.1016\/j.lfs.2025.123634_bb0105","doi-asserted-by":"crossref","first-page":"65","DOI":"10.5455\/jice.20160124113555","article-title":"Hepatoprotective effects of parsley, basil, and chicory aqueous extracts against dexamethasone-induced in experimental rats","volume":"5","author":"Soliman","year":"2016","journal-title":"J Intercult Ethnopharmacol."},{"issue":"4","key":"10.1016\/j.lfs.2025.123634_bb0110","first-page":"505","article-title":"Adverse effects of corticosteroids on the cardiovascular system","volume":"16","author":"Sholter","year":"2000","journal-title":"Can. J. Cardiol."},{"key":"10.1016\/j.lfs.2025.123634_bb0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.phrs.2021.106004","article-title":"Overexpression of PDE4D in mouse liver is sufficient to trigger NAFLD and hypertension in a CD36-TGF-\u03b21 pathway: therapeutic role of roflumilast","volume":"175","author":"Tao","year":"2022","journal-title":"Pharmacol. Res."},{"key":"10.1016\/j.lfs.2025.123634_bb0120","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3389\/fimmu.2016.00123","article-title":"The cAMP pathway as therapeutic target in autoimmune and inflammatory diseases","volume":"7","author":"Raker","year":"2016","journal-title":"Front. Immunol."},{"issue":"5","key":"10.1016\/j.lfs.2025.123634_bb0125","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.4049\/jimmunol.153.5.2052","article-title":"NF-kappa B and Sp1 regulate transcription of the human monocyte chemoattractant protein-1 gene","volume":"153","author":"Ueda","year":"1994","journal-title":"J. Immunol."},{"issue":"6","key":"10.1016\/j.lfs.2025.123634_bb0130","doi-asserted-by":"crossref","first-page":"G1083","DOI":"10.1152\/ajpgi.00568.2005","article-title":"Mechanisms of neutrophil-induced liver cell injury during hepatic ischemia-reperfusion and other acute inflammatory conditions","volume":"290","author":"Jaeschke","year":"2006","journal-title":"Am. J. Physiol. Gastrointest. Liver Physiol."},{"key":"10.1016\/j.lfs.2025.123634_bb0135","doi-asserted-by":"crossref","first-page":"1226044","DOI":"10.3389\/fcell.2023.1226044","article-title":"ROS induced lipid peroxidation and their role in ferroptosis","volume":"11","author":"Endale","year":"2023","journal-title":"Front. Cell Dev. Biol."},{"issue":"21","key":"10.1016\/j.lfs.2025.123634_bb0140","first-page":"2003","article-title":"Oxidative stress, mitochondrial damage and neurodegenerative diseases","volume":"8","author":"Guo","year":"2013","journal-title":"Neural Regen. Res."},{"issue":"3","key":"10.1016\/j.lfs.2025.123634_bb0145","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.smim.2014.05.004","article-title":"Regulation of NF-\u03baB by TNF family cytokines","volume":"26","author":"Hayden","year":"2014","journal-title":"Semin. Immunol."},{"key":"10.1016\/j.lfs.2025.123634_bb0150","first-page":"2","article-title":"Dopamine activates NF-\u03baB and primes the NLRP3 inflammasome in primary human macrophages. Brain Behav Immun","author":"Nolan","year":"2020","journal-title":"Health"},{"issue":"47","key":"10.1016\/j.lfs.2025.123634_bb0155","doi-asserted-by":"crossref","first-page":"18525","DOI":"10.1073\/pnas.0809677105","article-title":"Antioxidants reduce endoplasmic reticulum stress and improve protein secretion","volume":"105","author":"Malhotra","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"1","key":"10.1016\/j.lfs.2025.123634_bb0160","doi-asserted-by":"crossref","first-page":"434","DOI":"10.3390\/ijms14010434","article-title":"An involvement of oxidative stress in endoplasmic reticulum stress and its associated diseases","volume":"14","author":"Bhandary","year":"2012","journal-title":"Int. J. Mol. Sci."},{"key":"10.1016\/j.lfs.2025.123634_bb0165","article-title":"NF-\u03baB and its crosstalk with endoplasmic reticulum stress in atherosclerosis","volume":"9","author":"Li","year":"2022","journal-title":"Front Cardiovasc Med."},{"issue":"2","key":"10.1016\/j.lfs.2025.123634_bb0170","doi-asserted-by":"crossref","first-page":"183","DOI":"10.4062\/biomolther.2023.181","article-title":"Understanding the unfolded protein response (UPR) pathway: insights into neuropsychiatric disorders and therapeutic potentials","volume":"32","author":"Kim","year":"2024","journal-title":"Biomol Ther (Seoul)."},{"issue":"14","key":"10.1016\/j.lfs.2025.123634_bb0175","doi-asserted-by":"crossref","first-page":"6129","DOI":"10.1007\/s00253-020-10614-y","article-title":"Crosstalk between ER stress, NLRP3 inflammasome, and inflammation","volume":"104","author":"Li","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"issue":"4","key":"10.1016\/j.lfs.2025.123634_bb0180","doi-asserted-by":"crossref","first-page":"333","DOI":"10.4196\/kjpp.2014.18.4.333","article-title":"Exendin-4 improves nonalcoholic fatty liver disease by regulating glucose transporter 4 expression in Ob\/Ob mice","volume":"18","author":"Kim","year":"2014","journal-title":"Korean J Physiol Pharmacol."},{"issue":"5","key":"10.1016\/j.lfs.2025.123634_bb0185","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1007\/s13300-023-01393-6","article-title":"Practical guide to glucocorticoid induced Hyperglycaemia and diabetes","volume":"14","author":"Barker","year":"2023","journal-title":"Diabetes Therapy."},{"issue":"5","key":"10.1016\/j.lfs.2025.123634_bb0190","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1080\/13813455.2018.1479426","article-title":"Glucocorticoid exposure causes disrupted glucoregulation, cardiac inflammation and elevated dipeptidyl peptidase-4 activity independent of glycogen synthase kinase-3 in female rats","volume":"125","author":"Badmus","year":"2019","journal-title":"Arch. Physiol. Biochem."},{"key":"10.1016\/j.lfs.2025.123634_bb0195","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1016\/j.biochi.2019.09.011","article-title":"Protocatechuic acid exhibits hepatoprotective, vasculoprotective, antioxidant and insulin-like effects in dexamethasone-induced insulin-resistant rats","volume":"167","author":"El-Sonbaty","year":"2019","journal-title":"Biochimie"},{"issue":"4","key":"10.1016\/j.lfs.2025.123634_bb0200","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1111\/dom.12839","article-title":"The PDE4 inhibitor roflumilast reduces weight gain by increasing energy expenditure and leads to improved glucose metabolism","volume":"19","author":"M\u00f6llmann","year":"2017","journal-title":"Diabetes Obes. Metab."},{"key":"10.1016\/j.lfs.2025.123634_bb0205","doi-asserted-by":"crossref","DOI":"10.1016\/j.lfs.2024.122565","article-title":"Regulatory pathways and therapeutic potential of PDE4 in liver pathophysiology","volume":"345","author":"Zahra","year":"2024","journal-title":"Life Sci."}],"container-title":["Life Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320525002693?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0024320525002693?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,6,6]],"date-time":"2025-06-06T12:58:12Z","timestamp":1749214692000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0024320525002693"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":41,"alternative-id":["S0024320525002693"],"URL":"https:\/\/doi.org\/10.1016\/j.lfs.2025.123634","relation":{},"ISSN":["0024-3205"],"issn-type":[{"value":"0024-3205","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Roflumilast counteracts high-dose dexamethasone-induced steatohepatitis, metabolic abnormalities and aortic injury via inhibiting TNF-\u03b1\/NF-\u03baB, NLRP3\/IL-1\u03b2 and ER stress sensors","name":"articletitle","label":"Article Title"},{"value":"Life Sciences","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.lfs.2025.123634","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"123634"}}