{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:20:32Z","timestamp":1787624432274,"version":"build-2736575974"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"11","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,8]]},"DOI":"10.1007\/s00210-026-05436-0","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T03:19:48Z","timestamp":1779679188000},"page":"17505-17522","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disruption of upstream ox-LDL signaling and HSP90-mediated NLRP3 stability protects against experimental steatohepatitis"],"prefix":"10.1007","volume":"399","author":[{"given":"Alaa","family":"Karam","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amir Mohamed","family":"Abdelhamid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sameh","family":"Saber","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"issue":"1","key":"5436_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.0959-9673.2006.00465.x","volume":"87","author":"QM Anstee","year":"2006","unstructured":"Anstee QM, Goldin RD (2006) Mouse models in non-alcoholic fatty liver disease and steatohepatitis research. Int J Exp Pathol 87(1):1\u201316","journal-title":"Int J Exp Pathol"},{"issue":"1","key":"5436_CR2","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1186\/s11658-023-00462-9","volume":"28","author":"Y Chen","year":"2023","unstructured":"Chen Y, Ye X, Escames G, Lei W, Zhang X, Li M et al (2023) The NLRP3 inflammasome: contributions to inflammation-related diseases. Cell Mol Biol Lett 28(1):51","journal-title":"Cell Mol Biol Lett"},{"issue":"1","key":"5436_CR3","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1186\/s12876-015-0248-8","volume":"15","author":"L-W Chong","year":"2015","unstructured":"Chong L-W, Hsu Y-C, Lee T-F, Lin Y, Chiu Y-T, Yang K-C et al (2015) Fluvastatin attenuates hepatic steatosis-induced fibrogenesis in rats through inhibiting paracrine effect of hepatocyte on hepatic stellate cells. BMC Gastroenterol 15(1):22","journal-title":"BMC Gastroenterol"},{"issue":"1","key":"5436_CR4","doi-asserted-by":"publisher","first-page":"53","DOI":"10.14218\/JCTH.2014.00035","volume":"3","author":"B Delire","year":"2015","unstructured":"Delire B, St\u00e4rkel P, Leclercq I (2015) Animal models for fibrotic liver diseases: what we have, what we need, and what is under development. J Clin Transl Hepatol 3(1):53\u201366","journal-title":"J Clin Transl Hepatol"},{"key":"5436_CR5","doi-asserted-by":"publisher","first-page":"122966","DOI":"10.1016\/j.lfs.2024.122966","volume":"354","author":"EA Elmorsy","year":"2024","unstructured":"Elmorsy EA, Saber S, Hamad RS, Abdel-Reheim MA, Nadwa EH, Alibrahim AOE et al (2024) Modulating the HSP90 control over NF\u03baB\/NLRP3\/Caspase-1 axis is a new therapeutic target in the management of liver fibrosis: insights into the role of TAS-116 (Pimitespib). Life Sci 354:122966","journal-title":"Life Sci"},{"key":"5436_CR6","doi-asserted-by":"publisher","first-page":"107002","DOI":"10.1016\/j.ejps.2025.107002","volume":"206","author":"EA Elmorsy","year":"2025","unstructured":"Elmorsy EA, Elsisi HA, Alkhamiss AS, Alsoqih NS, Khodeir MM, Alsalloom AA et al (2025) Activation of SIRT1 by SRT1720 alleviates dyslipidemia, improves insulin sensitivity and exhibits liver-protective effects in diabetic rats on a high-fat diet: new insights into the SIRT1\/Nrf2\/NF\u03baB signaling pathway. Eur J Pharm Sci 206:107002","journal-title":"Eur J Pharm Sci"},{"key":"5436_CR7","doi-asserted-by":"publisher","first-page":"113460","DOI":"10.1016\/j.intimp.2024.113460","volume":"143","author":"F Elnaghy","year":"2024","unstructured":"Elnaghy F, Shehatou GSG, Abd El-Kader EM, Saber S (2024) Diltiazem mitigates acute liver injury by targeting NF\u03baB-TXNIP\/NLRP3 axis in rats: new insights beyond calcium channel blockade. Int Immunopharmacol 143:113460","journal-title":"Int Immunopharmacol"},{"issue":"1","key":"5436_CR8","doi-asserted-by":"publisher","first-page":"14436","DOI":"10.1038\/s41598-025-98894-0","volume":"15","author":"D Fujimoto","year":"2025","unstructured":"Fujimoto D, Umemoto S, Mizumoto T, Kanki T, Hata Y, Nishiguchi Y et al (2025) Alvespimycin is identified as a novel therapeutic agent for diabetic kidney disease by chemical screening targeting extracellular vesicles. Sci Rep 15(1):14436","journal-title":"Sci Rep"},{"key":"5436_CR9","doi-asserted-by":"publisher","first-page":"115452","DOI":"10.1016\/j.intimp.2025.115452","volume":"165","author":"RS Hamad","year":"2025","unstructured":"Hamad RS, Hasan WA, Saber S, Elmorsy EA, Farrag AA, Anwer HM et al (2025) MDL-800 protects against inflammatory and metabolic dysfunction: role of SIRT6 in the cross-regulation of NF\u03baB, AMPK, and PPAR signaling in rats. Int Immunopharmacol 165:115452","journal-title":"Int Immunopharmacol"},{"key":"5436_CR10","doi-asserted-by":"publisher","first-page":"115852","DOI":"10.1016\/j.intimp.2025.115852","volume":"168","author":"RS Hamad","year":"2026","unstructured":"Hamad RS, Hasan WA, Elmorsy EA, Farrag AA, Abdelaziz MA, Alalawy AI et al (2026) AGK2 and nicotinamide riboside reveal SIRT2\u055as protective role in a diabetic\u2013dietary rat model of NASH via deacetylation of NLRP3, LKB1, and FOXO3a and restoration of AMPK\u2013ACC\/PGC-1\u03b1\u2013Nrf2 signaling. Int Immunopharmacol 168:115852","journal-title":"Int Immunopharmacol"},{"issue":"6","key":"5436_CR11","doi-asserted-by":"publisher","first-page":"1827","DOI":"10.1002\/art.22632","volume":"56","author":"Y Haruna","year":"2007","unstructured":"Haruna Y, Morita Y, Yada T, Satoh M, Fox DA, Kashihara N (2007) Fluvastatin reverses endothelial dysfunction and increased vascular oxidative stress in rat adjuvant-induced arthritis. Arthritis Rheum 56(6):1827\u20131835","journal-title":"Arthritis Rheum"},{"issue":"4","key":"5436_CR12","doi-asserted-by":"publisher","first-page":"236","DOI":"10.1016\/S0011-393X(03)00060-2","volume":"64","author":"Y Homma","year":"2003","unstructured":"Homma Y, Homma K, Iizuka S, Iigaya K (2003) Effects of fluvastatin on plasma levels of low-density lipoprotein subfractions, oxidized low-density lipoprotein, and soluble adhesion molecules: a twenty-four-week, open-label, dose-increasing study. Curr Ther Res Clin Exp 64(4):236\u2013247","journal-title":"Curr Ther Res Clin Exp"},{"issue":"3","key":"5436_CR13","doi-asserted-by":"publisher","first-page":"101289","DOI":"10.1016\/j.jhepr.2024.101289","volume":"7","author":"V Houttu","year":"2025","unstructured":"Houttu V, Boulund U, Troelstra M, Csader S, Stols-Gon\u00e7alves D, Mak AL et al (2025) Deep phenotyping of patients with MASLD upon high-intensity interval training. JHEP Reports 7(3):101289","journal-title":"JHEP Reports"},{"issue":"5","key":"5436_CR14","doi-asserted-by":"publisher","first-page":"F1149","DOI":"10.1152\/ajprenal.00240.2017","volume":"313","author":"N Iguchi","year":"2017","unstructured":"Iguchi N, D\u00f6nmez M\u0130, Malykhina AP, Carrasco A, Wilcox DT (2017) Preventative effects of a HIF inhibitor, 17-DMAG, on partial bladder outlet obstruction-induced bladder dysfunction. Am J Physiol-Renal Physiol 313(5):F1149\u2013F1160","journal-title":"Am J Physiol-Renal Physiol"},{"key":"5436_CR15","doi-asserted-by":"publisher","first-page":"113000","DOI":"10.1016\/j.intimp.2024.113000","volume":"141","author":"AY Kira","year":"2024","unstructured":"Kira AY, Elmorsy EA, Hamad RS, Abdel-Reheim MA, Elhemely MA, El Adle KN et al (2024) Nicardipine-chitosan nanoparticles alleviate thioacetamide-induced acute liver injury by targeting NF\u03baB\/NLRP3\/IL-1\u03b2 signaling in rats: unraveling new roles beyond calcium channel blocking. Int Immunopharmacol 141:113000","journal-title":"Int Immunopharmacol"},{"issue":"2","key":"5436_CR16","doi-asserted-by":"publisher","first-page":"e220184","DOI":"10.1530\/JOE-22-0184","volume":"257","author":"S-Y Leu","year":"2023","unstructured":"Leu S-Y, Tsang Y-L, Ho L-C, Yang C-C, Shao A-N, Chang C-Y et al (2023) NLRP3 inflammasome activation, metabolic danger signals, and protein binding partners. J Endocrinol 257(2):e220184","journal-title":"J Endocrinol"},{"key":"5436_CR17","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24108970","author":"X Li","year":"2023","unstructured":"Li X, Du Y, Xue C, Kang X, Sun C, Peng H et al (2023) SIRT2 deficiency aggravates diet-induced nonalcoholic fatty liver disease through modulating gut microbiota and metabolites. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms24108970","journal-title":"Int J Mol Sci"},{"issue":"8","key":"5436_CR18","doi-asserted-by":"publisher","DOI":"10.3390\/ph16081123","volume":"16","author":"OA Mohammed","year":"2023","unstructured":"Mohammed OA, Abdel-Reheim MA, Saleh LA, Alamri MMS, Alfaifi J, Adam MIE et al (2023a) Alvespimycin exhibits potential anti-TGF-\u03b2 signaling in the setting of a proteasome activator in rats with bleomycin-induced pulmonary fibrosis: a promising novel approach. Pharmaceuticals Basel 16(8):1123","journal-title":"Pharmaceuticals Basel"},{"issue":"8","key":"5436_CR19","doi-asserted-by":"publisher","DOI":"10.3390\/ph16081080","volume":"16","author":"OA Mohammed","year":"2023","unstructured":"Mohammed OA, Abdel-Reheim MA, Alamri MMS, Alfaifi J, Adam MIE, Saleh LA et al (2023b) STA9090 as a potential therapeutic agent for liver fibrosis by modulating the HSP90\/T\u03b2RII\/proteasome interplay: novel insights from in vitro and in vivo investigations. Pharmaceuticals Basel 16(8):1080","journal-title":"Pharmaceuticals Basel"},{"issue":"21","key":"5436_CR20","doi-asserted-by":"publisher","DOI":"10.3390\/ijms252111386","volume":"25","author":"N Mosalmanzadeh","year":"2024","unstructured":"Mosalmanzadeh N, Pence BD (2024) Oxidized low-density lipoprotein and its role in immunometabolism. Int J Mol Sci 25(21):11386","journal-title":"Int J Mol Sci"},{"issue":"1","key":"5436_CR21","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-02418-9","volume":"15","author":"B Muffova","year":"2025","unstructured":"Muffova B, Kauerova S, Paukner K, Bartuskova H, Poledne R, Kralova Lesna I (2025) Anti-inflammatory effect of fluvastatin on polarized macrophages and its dependence on the mevalonate pathway. Sci Rep 15(1):19237","journal-title":"Sci Rep"},{"issue":"7","key":"5436_CR22","doi-asserted-by":"publisher","first-page":"e11765","DOI":"10.1371\/journal.pone.0011765","volume":"5","author":"K Rajam\u00e4ki","year":"2010","unstructured":"Rajam\u00e4ki K, Lappalainen J, \u00d6\u00f6rni K, V\u00e4lim\u00e4ki E, Matikainen S, Kovanen PT et al (2010) Cholesterol crystals activate the NLRP3 inflammasome in human macrophages: a novel link between cholesterol metabolism and inflammation. PLoS One 5(7):e11765","journal-title":"PLoS One"},{"issue":"6","key":"5436_CR23","doi-asserted-by":"publisher","first-page":"569","DOI":"10.1139\/cjpp-2017-0728","volume":"96","author":"S Saber","year":"2018","unstructured":"Saber S, Mahmoud AAA, Helal NS, El-Ahwany E, Abdelghany RH (2018) Renin\u2013angiotensin system inhibition ameliorates CCl4-induced liver fibrosis in mice through the inactivation of nuclear transcription factor kappa B. Can J Physiol Pharmacol 96(6):569\u2013576","journal-title":"Can J Physiol Pharmacol"},{"key":"5436_CR24","doi-asserted-by":"publisher","first-page":"113247","DOI":"10.1016\/j.biopha.2022.113247","volume":"153","author":"AA Shaaban","year":"2022","unstructured":"Shaaban AA, Abdelhamid AM, Shaker ME, Cavalu S, Maghiar AM, Alsayegh AA et al (2022) Combining the HSP90 inhibitor TAS-116 with metformin effectively degrades the NLRP3 and attenuates inflammasome activation in rats: a new management paradigm for ulcerative colitis. Biomed Pharmacother 153:113247","journal-title":"Biomed Pharmacother"},{"key":"5436_CR25","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.toxlet.2019.01.001","volume":"304","author":"L Sharma","year":"2019","unstructured":"Sharma L, Gupta D, Abdullah ST (2019) Thioacetamide potentiates high cholesterol and high fat diet induced steato-hepatitic changes in livers of C57BL\/6J mice: a novel eight weeks model of fibrosing NASH. Toxicol Lett 304:21\u201329","journal-title":"Toxicol Lett"},{"issue":"9","key":"5436_CR26","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj6289","volume":"10","author":"L Spel","year":"2024","unstructured":"Spel L, Hou C, Theodoropoulou K, Zaffalon L, Wang Z, Bertoni A et al (2024) HSP90\u03b2 controls NLRP3 autoactivation. Sci Adv 10(9):eadj6289","journal-title":"Sci Adv"},{"issue":"12","key":"5436_CR27","doi-asserted-by":"publisher","DOI":"10.3390\/cells12121648","volume":"12","author":"RAK Srivastava","year":"2023","unstructured":"Srivastava RAK (2023) A review of progress on targeting LDL receptor-dependent and -independent pathways for the treatment of hypercholesterolemia, a major risk factor of ASCVD. Cells Basel 12(12):1648","journal-title":"Cells Basel"},{"issue":"2","key":"5436_CR28","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/j.bpg.2011.02.004","volume":"25","author":"P Starkel","year":"2011","unstructured":"Starkel P, Leclercq IA (2011) Animal models for the study of hepatic fibrosis. Best Pract Res Clin Gastroenterol 25(2):319\u2013333","journal-title":"Best Pract Res Clin Gastroenterol"},{"issue":"9","key":"5436_CR29","doi-asserted-by":"publisher","DOI":"10.3390\/ph16091211","volume":"16","author":"P Theofilis","year":"2023","unstructured":"Theofilis P, Oikonomou E, Chasikidis C, Tsioufis K, Tousoulis D (2023) Inflammasomes in atherosclerosis\u2014from pathophysiology to treatment. Pharmaceuticals Basel 16(9):1211","journal-title":"Pharmaceuticals Basel"},{"key":"5436_CR30","doi-asserted-by":"crossref","unstructured":"Torres-Pe\u00f1a JD, Mart\u00edn-Piedra L, Fuentes-Jim\u00e9nez F (2021) Statins in non-alcoholic steatohepatitis. Front Cardiovasc Med Volume 8:2021","DOI":"10.3389\/fcvm.2021.777131"},{"issue":"1","key":"5436_CR31","doi-asserted-by":"publisher","first-page":"119","DOI":"10.4254\/wjh.v14.i1.119","volume":"14","author":"I Tzanaki","year":"2022","unstructured":"Tzanaki I, Agouridis AP, Kostapanos MS (2022) Is there a role of lipid-lowering therapies in the management of fatty liver disease? World J Hepatol 14(1):119\u2013139","journal-title":"World J Hepatol"},{"issue":"27","key":"5436_CR32","doi-asserted-by":"publisher","first-page":"9244","DOI":"10.1073\/pnas.0800163105","volume":"105","author":"KH Wrighton","year":"2008","unstructured":"Wrighton KH, Lin X, Feng X-H (2008) Critical regulation of TGF\u03b2 signaling by Hsp90. Proc Natl Acad Sci U S A 105(27):9244\u20139249","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"5436_CR33","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1007\/s12035-024-04290-6","volume":"62","author":"L Xiang","year":"2025","unstructured":"Xiang L, Lou J, Zhao J, Geng Y, Zhang J, Wu Y et al (2025) Underlying mechanism of lysosomal membrane permeabilization in CNS injury: a literature review. Mol Neurobiol 62(1):626\u2013642","journal-title":"Mol Neurobiol"},{"issue":"1","key":"5436_CR34","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41392-022-01119-3","volume":"7","author":"X Xu","year":"2022","unstructured":"Xu X, Poulsen KL, Wu L, Liu S, Miyata T, Song Q et al (2022) Targeted therapeutics and novel signaling pathways in non-alcohol-associated fatty liver\/steatohepatitis (NAFL\/NASH). Signal Transduct Target Ther 7(1):287","journal-title":"Signal Transduct Target Ther"},{"key":"5436_CR35","first-page":"0551","volume":"7","author":"J Yang","year":"2024","unstructured":"Yang J, Jiao C, Liu N, Liu W, Wang Y, Pan Y et al (2024) Polydatin-mediated inhibition of HSP90\u03b1 disrupts NLRP3 complexes and alleviates acute pancreatitis. Research (Wash D c) 7:0551","journal-title":"Research (Wash D c)"},{"issue":"4","key":"5436_CR36","doi-asserted-by":"publisher","first-page":"9605","DOI":"10.1097\/JS9.0000000000004619","volume":"112","author":"G Yu","year":"2026","unstructured":"Yu G, Zhao J, Zhu X, Yang N, Lou J, Chen Z et al (2026) 3,4-Dimethoxychalcone-induced caloric restriction inhibits PANoptosis to promote ischemic and diabetic skin flap survival: experimental studies. Int J Surg 112(4):9605\u20139613","journal-title":"Int J Surg"},{"issue":"1","key":"5436_CR37","doi-asserted-by":"publisher","first-page":"3264","DOI":"10.1186\/s12889-024-20663-x","volume":"24","author":"C Yuan","year":"2024","unstructured":"Yuan C, Zhang C, Geng X, Feng C, Su Y, Wu Y et al (2024) Associations of an overall healthy lifestyle with the risk of metabolic dysfunction-associated fatty liver disease. BMC Public Health 24(1):3264","journal-title":"BMC Public Health"},{"issue":"6","key":"5436_CR38","doi-asserted-by":"publisher","DOI":"10.3390\/nu15061517","volume":"15","author":"S Zivkovic","year":"2023","unstructured":"Zivkovic S, Maric G, Cvetinovic N, Lepojevic-Stefanovic D, Bozic Cvijan B (2023) Anti-inflammatory effects of lipid-lowering drugs and supplements\u2014a narrative review. Nutrients 15(6):1517","journal-title":"Nutrients"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05436-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05436-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05436-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T01:24:04Z","timestamp":1787621044000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05436-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,25]]},"references-count":38,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["5436"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05436-0","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,25]]},"assertion":[{"value":"1 March 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 May 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 May 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All animal procedures were conducted in accordance with national regulations, the European Directive 2010\/63\/EU, and ARRIVE 2.0 guidelines. Ethical approval for the study was obtained from the Institutional Animal Care and Use Committee (IACUC), Faculty of Pharmacy, Delta University for Science and Technology (approval number: FPDU2019\/119).","order":1,"name":"Ethics","label":"Ethical approval","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable. This study involved no human participants.","order":2,"name":"Ethics","label":"Consent to participate","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":4,"name":"Ethics","label":"Clinical trial number","group":{"name":"EthicsHeading","label":"Declarations"}}]}}