{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T20:12:45Z","timestamp":1790885565878,"version":"4.1.0"},"reference-count":91,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100007950","name":"Tanta University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100007950","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Genes Nutr"],"published-print":{"date-parts":[[2025,12]]},"DOI":"10.1186\/s12263-025-00784-7","type":"journal-article","created":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T13:33:49Z","timestamp":1764596029000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["The ameliorative effect of pioglitazone and\/or cod liver oil on hepatotoxicity induced by carbon tetrachloride in rats"],"prefix":"10.1186","volume":"20","author":[{"given":"Thoria","family":"Donia","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dina M.","family":"Elfeky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahar Saad El-Din","family":"Bessa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ehab","family":"Tousson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek M.","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4717-4481","authenticated-orcid":false,"given":"Marian N.","family":"Gerges","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"issue":"1","key":"784_CR1","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.cgh.2021.10.036","volume":"21","author":"C Griffin","year":"2023","unstructured":"Griffin C, et al. Underestimation of cirrhosis-related mortality in the medicare eligible population, 1999\u20132018. Clin Gastroenterol Hepatol. 2023;21(1):223\u20135. e3.","journal-title":"Clin Gastroenterol Hepatol"},{"issue":"1","key":"784_CR2","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1038\/s41392-024-02072-z","volume":"10","author":"C Gan","year":"2025","unstructured":"Gan C, et al. Liver diseases: epidemiology, causes, trends and predictions. Signal Transduct Target Therapy. 2025;10(1):33.","journal-title":"Signal Transduct Target Therapy"},{"key":"784_CR3","doi-asserted-by":"publisher","first-page":"683719","DOI":"10.3389\/fpubh.2021.683719","volume":"9","author":"R Melaram","year":"2021","unstructured":"Melaram R. Environmental risk factors implicated in liver disease: a mini-review. Front Public Health. 2021;9:683719.","journal-title":"Front Public Health"},{"issue":"2","key":"784_CR4","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1016\/j.jhep.2023.03.017","volume":"79","author":"H Devarbhavi","year":"2023","unstructured":"Devarbhavi H, et al. Global burden of liver disease: 2023 update. J Hepatol. 2023;79(2):516\u201337.","journal-title":"J Hepatol"},{"key":"784_CR5","doi-asserted-by":"crossref","unstructured":"Wazir H, et al. Diagnosis and treatment of liver disease: current trends and future directions. Cureus. 2023;15(12).","DOI":"10.7759\/cureus.49920"},{"issue":"4","key":"784_CR6","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1089\/wound.2019.1032","volume":"9","author":"EH Steen","year":"2020","unstructured":"Steen EH, et al. The role of the anti-inflammatory cytokine interleukin-10 in tissue fibrosis. Adv Wound Care. 2020;9(4):184\u201398.","journal-title":"Adv Wound Care"},{"key":"784_CR7","doi-asserted-by":"publisher","first-page":"645703","DOI":"10.3389\/fphar.2021.645703","volume":"12","author":"SY An","year":"2021","unstructured":"An SY, Petrescu AD, DeMorrow S. Targeting certain interleukins as novel treatment options for liver fibrosis. Front Pharmacol. 2021;12:645703.","journal-title":"Front Pharmacol"},{"issue":"10","key":"784_CR8","doi-asserted-by":"publisher","first-page":"e0241199","DOI":"10.1371\/journal.pone.0241199","volume":"15","author":"EdSG Amoras","year":"2020","unstructured":"Amoras EdSG, et al. Intrahepatic Interleukin 10 expression modulates fibrinogenesis during chronic HCV infection. PLoS ONE. 2020;15(10):e0241199.","journal-title":"PLoS ONE"},{"key":"784_CR9","doi-asserted-by":"publisher","first-page":"109445","DOI":"10.1016\/j.cellsig.2019.109445","volume":"66","author":"Y-H Huang","year":"2020","unstructured":"Huang Y-H, et al. Interleukin-10 induces senescence of activated hepatic stellate cells via STAT3-p53 pathway to attenuate liver fibrosis. Cell Signal. 2020;66:109445.","journal-title":"Cell Signal"},{"key":"784_CR10","doi-asserted-by":"crossref","unstructured":"Bai X, Su G, Zhai S. Recent advances in nanomedicine for the diagnosis and therapy of liver fibrosis. Nanomaterials (Basel). 2020;10(10).","DOI":"10.3390\/nano10101945"},{"issue":"3","key":"784_CR11","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1007\/s13679-023-00519-y","volume":"12","author":"ID Vachliotis","year":"2023","unstructured":"Vachliotis ID, Polyzos SA. The role of tumor necrosis factor-alpha in the pathogenesis and treatment of nonalcoholic fatty liver disease. Curr Obes Rep. 2023;12(3):191\u2013206.","journal-title":"Curr Obes Rep"},{"key":"784_CR12","doi-asserted-by":"crossref","unstructured":"Tiegs G, Horst AK. TNF in the liver: targeting a central player in inflammation. In: Seminars in Immunopathology. Springer; 2022.","DOI":"10.1007\/s00281-022-00910-2"},{"issue":"5","key":"784_CR13","doi-asserted-by":"publisher","first-page":"1290","DOI":"10.3390\/biomedicines11051290","volume":"11","author":"VJ Clemente-Su\u00e1rez","year":"2023","unstructured":"Clemente-Su\u00e1rez VJ, et al. The role of adipokines in health and disease. Biomedicines. 2023;11(5):1290.","journal-title":"Biomedicines"},{"issue":"10","key":"784_CR14","doi-asserted-by":"publisher","first-page":"708","DOI":"10.4254\/wjh.v10.i10.708","volume":"10","author":"W Udomsinprasert","year":"2018","unstructured":"Udomsinprasert W, Honsawek S, Poovorawan Y. Adiponectin as a novel biomarker for liver fibrosis. World J Hepatol. 2018;10(10):708.","journal-title":"World J Hepatol"},{"key":"784_CR15","doi-asserted-by":"publisher","first-page":"110785","DOI":"10.1016\/j.biopha.2020.110785","volume":"131","author":"SC Shabalala","year":"2020","unstructured":"Shabalala SC, et al. The effect of adiponectin in the pathogenesis of non-alcoholic fatty liver disease (NAFLD) and the potential role of polyphenols in the modulation of adiponectin signaling. Biomed Pharmacother. 2020;131:110785.","journal-title":"Biomed Pharmacother"},{"issue":"10","key":"784_CR16","doi-asserted-by":"publisher","first-page":"1853","DOI":"10.1111\/jgh.15926","volume":"37","author":"C Tontikidou","year":"2022","unstructured":"Tontikidou C, et al. Circulating adiponectin in patients with nonalcoholic fatty liver disease-related liver fibrosis: a systematic review and a meta\u2010analysis. J Gastroenterol Hepatol. 2022;37(10):1853\u201364.","journal-title":"J Gastroenterol Hepatol"},{"key":"784_CR17","doi-asserted-by":"publisher","first-page":"115871","DOI":"10.1016\/j.bcp.2023.115871","volume":"218","author":"SM Barbalho","year":"2023","unstructured":"Barbalho SM, Mendez-Sanchez N, Laurindo LF. AdipoRon and ADP355, adiponectin receptor agonists, in Metabolic-associated fatty liver disease (MAFLD) and nonalcoholic steatohepatitis (NASH): A systematic review. Biochem Pharmacol. 2023;218:115871.","journal-title":"Biochem Pharmacol"},{"key":"784_CR18","doi-asserted-by":"crossref","unstructured":"Heydari M, et al. Data on adiponectin from 2010 to 2020: therapeutic target and prognostic factor for liver diseases? Int J Mol Sci. 2020;21(15).","DOI":"10.3390\/ijms21155242"},{"key":"784_CR19","doi-asserted-by":"crossref","unstructured":"Al Neyadi SS, et al. Novel thiazolidinedione and rhodanine derivatives regulate glucose metabolism, improve insulin sensitivity, and activate the peroxisome proliferator-activated \u03b3 receptor. ACS Omega. 2024.","DOI":"10.1021\/acsomega.3c07149"},{"issue":"2","key":"784_CR20","doi-asserted-by":"publisher","first-page":"E163","DOI":"10.1152\/ajpendo.00023.2018","volume":"315","author":"S Kalavalapalli","year":"2018","unstructured":"Kalavalapalli S, et al. Pioglitazone improves hepatic mitochondrial function in a mouse model of nonalcoholic steatohepatitis. Am J Physiology-Endocrinology Metabolism. 2018;315(2):E163\u201373.","journal-title":"Am J Physiology-Endocrinology Metabolism"},{"issue":"4","key":"784_CR21","doi-asserted-by":"publisher","first-page":"411","DOI":"10.3233\/CBM-170157","volume":"20","author":"W Deng","year":"2017","unstructured":"Deng W, et al. Pioglitazone suppresses inflammation and fibrosis in nonalcoholic fatty liver disease by down-regulating PDGF and TIMP-2: evidence from in vitro study. Cancer Biomarkers. 2017;20(4):411\u20135.","journal-title":"Cancer Biomarkers"},{"key":"784_CR22","doi-asserted-by":"publisher","first-page":"615409","DOI":"10.3389\/fendo.2021.615409","volume":"12","author":"J Lian","year":"2021","unstructured":"Lian J, Fu J. Pioglitazone for NAFLD patients with prediabetes or type 2 diabetes mellitus: a meta-analysis. Front Endocrinol. 2021;12:615409.","journal-title":"Front Endocrinol"},{"key":"784_CR23","doi-asserted-by":"publisher","first-page":"108984","DOI":"10.1016\/j.diabres.2021.108984","volume":"178","author":"G Della Pepa","year":"2021","unstructured":"Della Pepa G, et al. Pioglitazone even at low dosage improves NAFLD in type 2 diabetes: clinical and pathophysiological insights from a subgroup of the TOSCA. IT randomised trial. Diabetes Res Clin Pract. 2021;178:108984.","journal-title":"Diabetes Res Clin Pract"},{"issue":"4","key":"784_CR24","doi-asserted-by":"publisher","first-page":"677","DOI":"10.62110\/sciencein.cbl.2024.v11.677","volume":"11","author":"SK Rai","year":"2024","unstructured":"Rai SK, et al. Pioglitazone and Ezetimibe combination improves liver histopathology and biochemistry in experimental MASH models. Chem Biology Lett. 2024;11(4):677\u2013677.","journal-title":"Chem Biology Lett"},{"key":"784_CR25","doi-asserted-by":"crossref","unstructured":"Sasie SD, et al. Impact of cod liver oil consumption in infants and children: a systematic review. 2022.","DOI":"10.21203\/rs.3.rs-2139509\/v1"},{"issue":"7","key":"784_CR26","doi-asserted-by":"publisher","first-page":"749","DOI":"10.1089\/jmf.2020.0114","volume":"24","author":"M Kontostathi","year":"2021","unstructured":"Kontostathi M, et al. Influence of omega-3 fatty acid-rich fish oils on hyperlipidemia: effect of eel, sardine, trout, and Cod oils on hyperlipidemic mice. J Med Food. 2021;24(7):749\u201355.","journal-title":"J Med Food"},{"key":"784_CR27","doi-asserted-by":"crossref","unstructured":"Mal M, et al. Role of cod liver oil in preventing myocardial infarction. Cureus. 2021;13(6).","DOI":"10.7759\/cureus.16067"},{"issue":"3","key":"784_CR28","doi-asserted-by":"publisher","first-page":"1067","DOI":"10.12991\/jrespharm.1694222","volume":"29","author":"Z Salsabila","year":"2025","unstructured":"Salsabila Z, et al. Incorporation of Cod liver oil to centella Asiatica (Gotu Kola) gummy candy as a cognitive enhancement supplement. J Res Pharm. 2025;29(3):1067\u201377.","journal-title":"J Res Pharm"},{"key":"784_CR29","doi-asserted-by":"crossref","unstructured":"Boucher BJ. Vitamin D deficiency in British South Asians, a persistent but avoidable problem associated with many health risks (including rickets, T2DM, CVD, COVID-19 and pregnancy complications): the case for correcting this deficiency. Endocr Connections. 2022;11(12).","DOI":"10.1530\/EC-22-0234"},{"issue":"1","key":"784_CR30","doi-asserted-by":"publisher","first-page":"bgae081","DOI":"10.1093\/carcin\/bgae081","volume":"46","author":"MI Garay","year":"2025","unstructured":"Garay MI, et al. Novel inhibitory effect of Omega-3 fatty acids regulating pancreatic cancer progression. Carcinogenesis. 2025;46(1):bgae081.","journal-title":"Carcinogenesis"},{"key":"784_CR31","doi-asserted-by":"publisher","first-page":"1192099","DOI":"10.3389\/fpubh.2023.1192099","volume":"11","author":"MS Vell","year":"2023","unstructured":"Vell MS, et al. Omega-3 intake is associated with liver disease protection. Front Public Health. 2023;11:1192099.","journal-title":"Front Public Health"},{"key":"784_CR32","first-page":"100142","volume":"13","author":"P Das","year":"2024","unstructured":"Das P, et al. Advances in therapeutic applications of fish oil: A review. Measurement: Food. 2024;13:100142.","journal-title":"Measurement: Food"},{"key":"784_CR33","doi-asserted-by":"publisher","first-page":"1524830","DOI":"10.3389\/fnut.2025.1524830","volume":"12","author":"L Zhou","year":"2025","unstructured":"Zhou L, Sun D, Bai H. Efficacy of fish oil supplementation on metabolic dysfunction-associated steatotic liver disease: a meta-analysis. Front Nutr. 2025;12:1524830.","journal-title":"Front Nutr"},{"issue":"4","key":"784_CR34","first-page":"1261","volume":"57","author":"F Ionic\u0103","year":"2016","unstructured":"Ionic\u0103 F, et al. Antifibrotic action of Telmisartan in experimental carbon tetrachloride-induced liver fibrosis in Wistar rats. Romanian J Morphology Embryol = Revue Roumaine De Morphologie Et Embryologie. 2016;57(4):1261\u201372.","journal-title":"Romanian J Morphology Embryol = Revue Roumaine De Morphologie Et Embryologie"},{"issue":"7","key":"784_CR35","doi-asserted-by":"publisher","first-page":"748","DOI":"10.1080\/10715762.2019.1624742","volume":"53","author":"RR Radwan","year":"2019","unstructured":"Radwan RR, Hasan HF. Pioglitazone ameliorates hepatic damage in irradiated rats via regulating anti-inflammatory and antifibrogenic signalling pathways. Free Radic Res. 2019;53(7):748\u201357.","journal-title":"Free Radic Res"},{"issue":"1","key":"784_CR36","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1179\/1351000214Y.0000000097","volume":"20","author":"I Sherif","year":"2015","unstructured":"Sherif I, Al-Gayyar M. Cod liver oil in sodium nitrite induced hepatic injury: does it have a potential protective effect? Redox Rep. 2015;20(1):11\u20136.","journal-title":"Redox Rep"},{"issue":"4","key":"784_CR37","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta delta C(T)) method. Methods. 2001;25(4):402\u20138.","journal-title":"Methods"},{"key":"784_CR38","unstructured":"Bancroft JD, Layton C, Suvarna SK. Bancroft\u2019s theory and practice of histological techniques. Churchill Livingstone Elsevier; 2013."},{"issue":"5","key":"784_CR39","doi-asserted-by":"publisher","first-page":"743","DOI":"10.1016\/S0168-8278(99)80123-8","volume":"30","author":"Y Suzuki","year":"1999","unstructured":"Suzuki Y, et al. Histological changes in liver biopsies after one year of lamivudine treatment in patients with chronic hepatitis B infection. J Hepatol. 1999;30(5):743\u20138.","journal-title":"J Hepatol"},{"issue":"4","key":"784_CR40","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1177\/29.4.6166661","volume":"29","author":"S-M Hsu","year":"1981","unstructured":"Hsu S-M, Raine L, Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochemistry. 1981;29(4):577\u201380.","journal-title":"J Histochem Cytochemistry"},{"issue":"8","key":"784_CR41","doi-asserted-by":"publisher","first-page":"1619","DOI":"10.1021\/acs.chemrestox.9b00164","volume":"32","author":"TB Wahed","year":"2019","unstructured":"Wahed TB, et al. Protective role of syzygium cymosum leaf extract against carbofuran-induced hematological and hepatic toxicities. Chem Res Toxicol. 2019;32(8):1619\u201329.","journal-title":"Chem Res Toxicol"},{"issue":"2","key":"784_CR42","doi-asserted-by":"publisher","first-page":"383","DOI":"10.1016\/j.intimp.2014.05.014","volume":"21","author":"NO Al-Harbi","year":"2014","unstructured":"Al-Harbi NO, et al. Carbon tetrachloride-induced hepatotoxicity in rat is reversed by treatment with riboflavin. Int Immunopharmacol. 2014;21(2):383\u20138.","journal-title":"Int Immunopharmacol"},{"issue":"9","key":"784_CR43","doi-asserted-by":"publisher","first-page":"1124","DOI":"10.2174\/0115665240257603230919103539","volume":"24","author":"MM Fareed","year":"2024","unstructured":"Fareed MM, et al. Deciphering molecular mechanisms of carbon tetrachloride-induced hepatotoxicity: A brief systematic review. Curr Mol Med. 2024;24(9):1124\u201334.","journal-title":"Curr Mol Med"},{"issue":"5","key":"784_CR44","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1016\/j.bj.2020.04.011","volume":"44","author":"MR Khalil","year":"2021","unstructured":"Khalil MR, et al. Therapeutic effect of bone marrow mesenchymal stem cells in a rat model of carbon tetrachloride induced liver fibrosis. Biomedical J. 2021;44(5):598\u2013610.","journal-title":"Biomedical J"},{"key":"784_CR45","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1016\/j.nutos.2022.06.004","volume":"44","author":"D Akinloye","year":"2022","unstructured":"Akinloye D, et al. Acalypha Wilkesiana Java white restored carbon tetrachloride (CCl4)-induced reno-hepatic tissue dysfunction in female albino rats. Clin Nutr Open Sci. 2022;44:66\u201391.","journal-title":"Clin Nutr Open Sci"},{"issue":"2","key":"784_CR46","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1515\/reveh-2020-0048","volume":"36","author":"V Unsal","year":"2021","unstructured":"Unsal V, Cicek M, Sabancilar \u0130. Toxicity of carbon tetrachloride, free radicals and role of antioxidants. Rev Environ Health. 2021;36(2):279\u201395.","journal-title":"Rev Environ Health"},{"issue":"7","key":"784_CR47","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.3748\/wjg.v10.i7.1047","volume":"10","author":"GJ Yuan","year":"2004","unstructured":"Yuan GJ, Zhang ML, Gong ZJ. Effects of PPARg agonist Pioglitazone on rat hepatic fibrosis. World J Gastroenterol. 2004;10(7):1047\u201351.","journal-title":"World J Gastroenterol"},{"issue":"3","key":"784_CR48","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1007\/s00535-017-1415-1","volume":"53","author":"Y Sumida","year":"2018","unstructured":"Sumida Y, Yoneda M. Current and future Pharmacological therapies for NAFLD\/NASH. J Gastroenterol. 2018;53(3):362\u201376.","journal-title":"J Gastroenterol"},{"key":"784_CR49","doi-asserted-by":"publisher","first-page":"1111430","DOI":"10.3389\/fendo.2023.1111430","volume":"14","author":"Z Wang","year":"2023","unstructured":"Wang Z, et al. Response to Pioglitazone in non-alcoholic fatty liver disease patients with vs. without type 2 diabetes: a meta-analysis of randomized controlled trials. Front Endocrinol. 2023;14:1111430.","journal-title":"Front Endocrinol"},{"issue":"11","key":"784_CR50","doi-asserted-by":"publisher","first-page":"1435","DOI":"10.3109\/13880209.2013.796564","volume":"51","author":"MF Salama","year":"2013","unstructured":"Salama MF, et al. Hepatoprotective effects of Cod liver oil against sodium nitrite toxicity in rats. Pharm Biol. 2013;51(11):1435\u201343.","journal-title":"Pharm Biol"},{"issue":"3","key":"784_CR51","doi-asserted-by":"publisher","first-page":"253","DOI":"10.1515\/jbcpp-2013-0143","volume":"26","author":"AE Omugba","year":"2015","unstructured":"Omugba AE, et al. Modulatory effects of Cod liver oil on the antioxidant status and oxidative stress induced by acute exposure to carbon tetrachloride (CCL4) in experimental animal models. J Basic Clin Physiol Pharmacol. 2015;26(3):253\u20137.","journal-title":"J Basic Clin Physiol Pharmacol"},{"issue":"4","key":"784_CR52","doi-asserted-by":"publisher","first-page":"538","DOI":"10.5115\/acb.23.101","volume":"56","author":"GN Ouais","year":"2023","unstructured":"Ouais GN, Hassan DM. A comparative study on the hepatoprotective effect of selenium-nanoparticles and dates flesh extract on carbon tetrachloride induced liver damage in albino rats. Anat Cell Biology. 2023;56(4):538\u201351.","journal-title":"Anat Cell Biology"},{"issue":"11","key":"784_CR53","doi-asserted-by":"publisher","first-page":"3044","DOI":"10.3390\/cells10113044","volume":"10","author":"S-Y Liu","year":"2021","unstructured":"Liu S-Y, et al. Pioglitazone ameliorates acute endotoxemia-induced acute on chronic renal dysfunction in cirrhotic ascitic rats. Cells. 2021;10(11):3044.","journal-title":"Cells"},{"issue":"5","key":"784_CR54","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3892\/etm.2023.11931","volume":"25","author":"Z Wu","year":"2023","unstructured":"Wu Z, et al. The hepatoprotective effect of aspirin on carbon tetrachloride\u2013induced hepatic fibrosis via Inhibition of TGF\u03b2\u20131 pathway and pro\u2013inflammatory cytokines IL\u20131\u03b2 and COX\u20132 in rats. Experimental Therapeutic Med. 2023;25(5):232.","journal-title":"Experimental Therapeutic Med"},{"issue":"2","key":"784_CR55","doi-asserted-by":"publisher","first-page":"e88498","DOI":"10.1371\/journal.pone.0088498","volume":"9","author":"X Huang","year":"2014","unstructured":"Huang X, et al. Protection effect of Kallistatin on carbon tetrachloride-induced liver fibrosis in rats via antioxidative stress. PLoS ONE. 2014;9(2):e88498.","journal-title":"PLoS ONE"},{"key":"784_CR56","doi-asserted-by":"crossref","unstructured":"Kim J, Seki E. Hyaluronan in liver fibrosis: basic mechanisms, clinical implications, and therapeutic targets. Hepatol Commun. 2023;7(4).","DOI":"10.1097\/HC9.0000000000000083"},{"issue":"8","key":"784_CR57","first-page":"832","volume":"18","author":"SK Mohan","year":"2015","unstructured":"Mohan SK, Veeraraghavan VP, Jainu M. Effect of pioglitazone, Quercetin and hydroxy citric acid on extracellular matrix components in experimentally induced non-alcoholic steatohepatitis. Iran J Basic Med Sci. 2015;18(8):832\u20136.","journal-title":"Iran J Basic Med Sci"},{"issue":"7","key":"784_CR58","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.3748\/wjg.v10.i7.1047","volume":"10","author":"G-J Yuan","year":"2004","unstructured":"Yuan G-J, Zhang M-L, Gong Z-J. Effects of PPARg agonist Pioglitazone on rat hepatic fibrosis. World J Gastroenterol. 2004;10(7):1047.","journal-title":"World J Gastroenterol"},{"issue":"6","key":"784_CR59","first-page":"9470","volume":"8","author":"Y Wu","year":"2015","unstructured":"Wu Y, et al. Protective effect of the \u03c9-3 polyunsaturated fatty acids on the schistosomiasis liver fibrosis in mice. Int J Clin Exp Med. 2015;8(6):9470\u20136.","journal-title":"Int J Clin Exp Med"},{"issue":"2","key":"784_CR60","doi-asserted-by":"publisher","first-page":"2491","DOI":"10.1021\/acsomega.3c07126","volume":"9","author":"AA Sorour","year":"2024","unstructured":"Sorour AA, et al. Structure modification converts the hepatotoxic Tacrine into novel hepatoprotective analogs. ACS Omega. 2024;9(2):2491\u2013503.","journal-title":"ACS Omega"},{"issue":"1","key":"784_CR61","doi-asserted-by":"publisher","first-page":"215","DOI":"10.3390\/molecules23010215","volume":"23","author":"X Peng","year":"2018","unstructured":"Peng X, et al. Curcumin attenuates on carbon tetrachloride-induced acute liver injury in mice via modulation of the Nrf2\/HO-1 and TGF-\u03b21\/Smad3 pathway. Molecules. 2018;23(1):215.","journal-title":"Molecules"},{"issue":"1","key":"784_CR62","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/j.jfda.2017.04.007","volume":"26","author":"Y-J Chiu","year":"2018","unstructured":"Chiu Y-J, et al. Hepatoprotective effect of the ethanol extract of polygonum orientale on carbon tetrachloride-induced acute liver injury in mice. J Food Drug Anal. 2018;26(1):369\u201379.","journal-title":"J Food Drug Anal"},{"issue":"1","key":"784_CR63","doi-asserted-by":"publisher","first-page":"15245","DOI":"10.1038\/s41598-023-42250-7","volume":"13","author":"SM El-Kot","year":"2023","unstructured":"El-Kot SM, et al. Effect of Silymarin on the relative gene expressions of some inflammatory cytokines in the liver of CCl4-intoxicated male rats. Sci Rep. 2023;13(1):15245.","journal-title":"Sci Rep"},{"issue":"13","key":"784_CR64","first-page":"2316","volume":"125","author":"L Su","year":"2012","unstructured":"Su L. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats. Chin Med J. 2012;125(13):2316\u201321.","journal-title":"Chin Med J"},{"issue":"13","key":"784_CR65","first-page":"2316","volume":"125","author":"JS Zhao","year":"2012","unstructured":"Zhao JS, et al. Pioglitazone ameliorates nonalcoholic steatohepatitis by down-regulating hepatic nuclear factor-kappa B and cyclooxygenases-2 expression in rats. Chin Med J (Engl). 2012;125(13):2316\u201321.","journal-title":"Chin Med J (Engl)"},{"key":"784_CR66","doi-asserted-by":"publisher","first-page":"108391","DOI":"10.1016\/j.pharmthera.2023.108391","volume":"245","author":"H Chen","year":"2023","unstructured":"Chen H, et al. PPAR-\u03b3 signaling in nonalcoholic fatty liver disease: pathogenesis and therapeutic targets. Pharmacol Ther. 2023;245:108391.","journal-title":"Pharmacol Ther"},{"issue":"1","key":"784_CR67","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1007\/s10571-017-0554-5","volume":"38","author":"S Villapol","year":"2018","unstructured":"Villapol S. Roles of peroxisome proliferator-activated receptor gamma on brain and peripheral inflammation. Cell Mol Neurobiol. 2018;38(1):121\u201332.","journal-title":"Cell Mol Neurobiol"},{"issue":"5","key":"784_CR68","doi-asserted-by":"publisher","first-page":"422","DOI":"10.1016\/j.nutres.2013.02.011","volume":"33","author":"MEP Nobre","year":"2013","unstructured":"Nobre MEP, et al. Eicosapentaenoic acid and docosahexaenoic acid exert anti-inflammatory and antinociceptive effects in rodents at low doses. Nutr Res. 2013;33(5):422\u201333.","journal-title":"Nutr Res"},{"key":"784_CR69","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.toxrep.2024.01.007","volume":"12","author":"AI Algefare","year":"2024","unstructured":"Algefare AI, et al. Geraniol prevents CCl4-induced hepatotoxicity via suppression of hepatic oxidative stress, pro-inflammation and apoptosis in rats. Toxicol Rep. 2024;12:128\u201334.","journal-title":"Toxicol Rep"},{"issue":"1","key":"784_CR70","first-page":"469","volume":"70","author":"AB Hsouna","year":"2023","unstructured":"Hsouna AB, et al. Immunomodulatory effect of Linalool (Lin) against CCl4-induced hepatotoxicity and oxidative damage in rats. Biotechnol Appl Chem. 2023;70(1):469\u201377.","journal-title":"Biotechnol Appl Chem"},{"issue":"3","key":"784_CR71","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1002\/oby.21769","volume":"25","author":"Z Xu","year":"2017","unstructured":"Xu Z, et al. PPAR-\u03b3 agonist ameliorates liver pathology accompanied by increasing regulatory B and T cells in high\u2010fat\u2010diet mice. Obesity. 2017;25(3):581\u201390.","journal-title":"Obesity"},{"issue":"3","key":"784_CR72","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.tem.2015.01.002","volume":"26","author":"NK Saxena","year":"2015","unstructured":"Saxena NK, Anania FA. Adipocytokines and hepatic fibrosis. Trends Endocrinol Metabolism. 2015;26(3):153\u201361.","journal-title":"Trends Endocrinol Metabolism"},{"issue":"4","key":"784_CR73","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1292\/jvms.17-0641","volume":"80","author":"H Hashimoto","year":"2018","unstructured":"Hashimoto H, et al. Adiponectin deficiency-induced diabetes increases TNF\u03b1 and FFA via downregulation of PPAR\u03b1. J Vet Med Sci. 2018;80(4):662\u20136.","journal-title":"J Vet Med Sci"},{"issue":"6","key":"784_CR74","doi-asserted-by":"publisher","first-page":"1796","DOI":"10.1053\/j.gastro.2003.08.029","volume":"125","author":"Y Kamada","year":"2003","unstructured":"Kamada Y, et al. Enhanced carbon tetrachloride-induced liver fibrosis in mice lacking adiponectin. Gastroenterology. 2003;125(6):1796\u2013807.","journal-title":"Gastroenterology"},{"issue":"10","key":"784_CR75","doi-asserted-by":"publisher","first-page":"e110405","DOI":"10.1371\/journal.pone.0110405","volume":"9","author":"P Kumar","year":"2014","unstructured":"Kumar P, et al. Adiponectin agonist ADP355 attenuates CCl4-induced liver fibrosis in mice. PLoS ONE. 2014;9(10):e110405.","journal-title":"PLoS ONE"},{"issue":"1","key":"784_CR76","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s41936-021-00224-z","volume":"82","author":"S Elmasry","year":"2021","unstructured":"Elmasry S, Moawad M. The hepatoprotective effect of gooseberry and black mulberry extracts against carbon tetrachloride-induced liver injury in rats. J Basic Appl Zool. 2021;82(1):33.","journal-title":"J Basic Appl Zool"},{"issue":"9","key":"784_CR77","doi-asserted-by":"publisher","first-page":"1824","DOI":"10.3390\/antiox11091824","volume":"11","author":"AM Alnuqaydan","year":"2022","unstructured":"Alnuqaydan AM, et al. Tamarix articulata induced prevention of hepatotoxicity effects of in vivo carbon tetrachloride by modulating pro-inflammatory serum and antioxidant enzymes to reverse the liver fibrosis. Antioxidants. 2022;11(9):1824.","journal-title":"Antioxidants"},{"key":"784_CR78","doi-asserted-by":"crossref","unstructured":"Tailleux A, Wouters K, Staels B. Roles of PPARs in NAFLD: potential therapeutic targets. Biochim Biophys Acta Mol Cell Biol Lipids. 2012;1821(5):809\u201318.","DOI":"10.1016\/j.bbalip.2011.10.016"},{"issue":"12","key":"784_CR79","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1111\/1440-1681.12020","volume":"39","author":"W Zhang","year":"2012","unstructured":"Zhang W, et al. Thiazolidinediones improve hepatic fibrosis in rats with non-alcoholic steatohepatitis by activating the adenosine monophosphate\u2010activated protein kinase signalling pathway. Clin Exp Pharmacol Physiol. 2012;39(12):1026\u201333.","journal-title":"Clin Exp Pharmacol Physiol"},{"issue":"7","key":"784_CR80","doi-asserted-by":"publisher","first-page":"679","DOI":"10.1111\/j.1365-2036.2009.04230.x","volume":"31","author":"G Masterton","year":"2010","unstructured":"Masterton G, Plevris J, Hayes P. omega-3 fatty acids\u2013a promising novel therapy for non\u2010alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010;31(7):679\u201392.","journal-title":"Aliment Pharmacol Ther"},{"issue":"16","key":"784_CR81","doi-asserted-by":"publisher","first-page":"e23889","DOI":"10.1096\/fj.202400733R","volume":"38","author":"WF Nierath","year":"2024","unstructured":"Nierath WF, et al. GSK805 inhibits alpha-smooth muscle expression and modulates liver inflammation without impairing the well\u2010being of mice. FASEB J. 2024;38(16):e23889.","journal-title":"FASEB J"},{"issue":"3","key":"784_CR82","doi-asserted-by":"publisher","first-page":"461","DOI":"10.1007\/s10616-016-9948-3","volume":"69","author":"A Inoue","year":"2017","unstructured":"Inoue A, et al. Regulation of matrix metalloproteinase-1 and alpha-smooth muscle actin expression by interleukin-1 alpha and tumour necrosis factor alpha in hepatic stellate cells. Cytotechnology. 2017;69(3):461\u20138.","journal-title":"Cytotechnology"},{"key":"784_CR83","doi-asserted-by":"publisher","first-page":"672658","DOI":"10.3389\/fmed.2021.672658","volume":"8","author":"HT Nga","year":"2021","unstructured":"Nga HT, et al. Interleukin-10 attenuates liver fibrosis exacerbated by thermoneutrality. Front Med. 2021;8:672658.","journal-title":"Front Med"},{"issue":"12","key":"784_CR84","doi-asserted-by":"publisher","first-page":"1327","DOI":"10.1007\/s00109-015-1313-z","volume":"93","author":"Z Dong","year":"2015","unstructured":"Dong Z, et al. Adiponectin attenuates liver fibrosis by inducing nitric oxide production of hepatic stellate cells. J Mol Med. 2015;93(12):1327\u201339.","journal-title":"J Mol Med"},{"issue":"3","key":"784_CR85","doi-asserted-by":"publisher","first-page":"840","DOI":"10.1111\/jcmm.17131","volume":"26","author":"WV Zheng","year":"2022","unstructured":"Zheng WV, et al. Uridine alleviates carbon tetrachloride-induced liver fibrosis by regulating the activity of liver\u2010related cells. J Cell Mol Med. 2022;26(3):840\u201354.","journal-title":"J Cell Mol Med"},{"key":"784_CR86","doi-asserted-by":"publisher","first-page":"113020","DOI":"10.1016\/j.biopha.2022.113020","volume":"150","author":"N Zein","year":"2022","unstructured":"Zein N, et al. Oral supplementation of Policosanol alleviates carbon tetrachloride-induced liver fibrosis in rats. Biomed Pharmacother. 2022;150:113020.","journal-title":"Biomed Pharmacother"},{"key":"784_CR87","doi-asserted-by":"publisher","first-page":"109516","DOI":"10.1016\/j.biopha.2019.109516","volume":"121","author":"X Huang","year":"2020","unstructured":"Huang X, et al. Extract of averrhoacarambola L.(Oxalidaceae) roots ameliorates carbon tetrachloride-induced hepatic fibrosis in rats. Biomed Pharmacother. 2020;121:109516.","journal-title":"Biomed Pharmacother"},{"issue":"3","key":"784_CR88","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1139\/cjpp-2020-0159","volume":"99","author":"SA Ibrahim","year":"2021","unstructured":"Ibrahim SA, et al. Antifibrotic effects of Bezafibrate and Pioglitazone against thioacetamide-induced liver fibrosis in albino rats. Can J Physiol Pharmacol. 2021;99(3):313\u201320.","journal-title":"Can J Physiol Pharmacol"},{"key":"784_CR89","doi-asserted-by":"publisher","first-page":"122480","DOI":"10.1016\/j.lfs.2024.122480","volume":"340","author":"MM Ansari","year":"2024","unstructured":"Ansari MM, et al. Oral delivery of aescin-loaded gelatin nanoparticles ameliorates carbon tetrachloride-induced hepatotoxicity in Wistar rats. Life Sci. 2024;340:122480.","journal-title":"Life Sci"},{"issue":"7","key":"784_CR90","doi-asserted-by":"publisher","first-page":"1020","DOI":"10.1136\/gut.2005.079194","volume":"55","author":"IA Leclercq","year":"2006","unstructured":"Leclercq IA, et al. Limited therapeutic efficacy of Pioglitazone on progression of hepatic fibrosis in rats. Gut. 2006;55(7):1020\u20139.","journal-title":"Gut"},{"issue":"1","key":"784_CR91","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.phanu.2017.01.002","volume":"5","author":"AS Basheer","year":"2017","unstructured":"Basheer AS, et al. Hepatoprotective and antioxidant effects of fish oil on isoniazid-rifampin induced hepatotoxicity in rats. PharmaNutrition. 2017;5(1):29\u201333.","journal-title":"PharmaNutrition"}],"container-title":["Genes & Nutrition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12263-025-00784-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12263-025-00784-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12263-025-00784-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T14:51:30Z","timestamp":1781621490000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s12263-025-00784-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12]]},"references-count":91,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2025,12]]}},"alternative-id":["784"],"URL":"https:\/\/doi.org\/10.1186\/s12263-025-00784-7","relation":{},"ISSN":["1555-8932","1865-3499"],"issn-type":[{"value":"1555-8932","type":"print"},{"value":"1865-3499","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12]]},"assertion":[{"value":"23 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 October 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 December 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"25"}}