{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T18:16:18Z","timestamp":1793038578633,"version":"4.5.0"},"reference-count":116,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Arsenic trioxide (ATO) has shown substantial efficacy in the treatment of patients with acute promyelocytic leukemia, and the utilization of ATO as a potential treatment for other tumors is currently being investigated; thus, its clinical application is becoming more widespread. However, the toxicity of ATO has prevented many patients from receiving this highly beneficial treatment. The clinical features, mechanisms, and preventive measures for ATO hepatotoxicity, as well as potential curative strategies, are discussed in this review. This review not only discusses existing drugs for the treatment of hepatotoxicity but also focuses on potential future therapeutic agents, providing forward-looking guidance for the clinical use of small molecule extracts, trace elements, antidiabetic drugs, and vitamins.<\/jats:p>","DOI":"10.3389\/fphar.2025.1536388","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T06:39:42Z","timestamp":1740033582000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":23,"title":["Hepatotoxicity induced by arsenic trioxide: clinical features, mechanisms, preventive and potential therapeutic strategies"],"prefix":"10.3389","volume":"16","author":[{"given":"Jun","family":"Wen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aiwen","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziliang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoxiao","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaoling","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark R.","family":"Litzow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiuju","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"111325","DOI":"10.1016\/j.intimp.2023.111325","article-title":"Dapagliflozin alleviates arsenic trioxide-induced hepatic injury in rats via modulating PI3K\/AkT\/mTOR, STAT3\/SOCS3\/p53\/MDM2 signaling pathways and miRNA-21, miRNA-122 expression","volume":"127","author":"Abdel-Wahab","year":"2024","journal-title":"Int. Immunopharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"5795","DOI":"10.1182\/blood-2011-02-329367","article-title":"Revisiting the differentiation paradigm in acute promyelocytic leukemia","volume":"117","author":"Ablain","year":"2011","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1396","DOI":"10.3109\/0886022X.2015.1074462","article-title":"Naringin ameliorates sodium arsenite-induced renal and hepatic toxicity in rats: decisive role of KIM-1, Caspase-3, TGF-\u03b2, and TNF-\u03b1","volume":"37","author":"Adil","year":"2015","journal-title":"Ren. Fail"},{"key":"B4","doi-asserted-by":"publisher","first-page":"3199","DOI":"10.3390\/ijerph16173199","article-title":"Co-exposure to SiO(2) nanoparticles and arsenic induced augmentation of oxidative stress and mitochondria-dependent apoptosis in human cells","volume":"16","author":"Ahamed","year":"2019","journal-title":"Int. J. Environ. Res. Public Health"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.22038\/IJBMS.2017.9567","article-title":"Protective effect of metformin on toxicity of butyric acid and arsenic in isolated liver mitochondria and langerhans islets in male mice: an in vitro study","volume":"20","author":"Ahangarpour","year":"2017","journal-title":"Iran. J. Basic Med. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"127067","DOI":"10.1016\/j.jtemb.2022.127067","article-title":"Thymoquinone supplementation mitigates arsenic-induced cytotoxic and genotoxic alterations in rat liver","volume":"74","author":"Alam","year":"2022","journal-title":"J. Trace Elem. Med. Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/j.tips.2017.02.005","article-title":"Ferroptosis inhibition: mechanisms and opportunities","volume":"38","author":"Angeli","year":"2017","journal-title":"Trends Pharmacol. Sci."},{"key":"B8","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/0891-5849(96)00174-8","article-title":"Arsenic induces oxidant stress and NF-kappa B activation in cultured aortic endothelial cells","volume":"21","author":"Barchowsky","year":"1996","journal-title":"Free Radic. Biol. Med."},{"key":"B9","doi-asserted-by":"publisher","first-page":"377","DOI":"10.29261\/pakvetj\/2024.154","article-title":"Protective effects of moringa oleifera leaf extract against silver nanoparticles and arsenic induced hepatotoxicity in rats","volume":"44","author":"Bashir","year":"2024","journal-title":"Pak Vet. J."},{"key":"B10","first-page":"305","article-title":"Protective effects of eugenol against hepatotoxicity induced by arsenic trioxide: an antileukemic drug","volume":"43","author":"Binu","year":"2018","journal-title":"Iran. J. Med. Sci."},{"key":"B11","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.etap.2017.12.005","article-title":"Acetyl-l-carnitine attenuates arsenic-induced liver injury by abrogation of mitochondrial dysfunction, inflammation, and apoptosis in rats","volume":"58","author":"Bodaghi-Namileh","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1517\/14656566.2012.677436","article-title":"Arsenic trioxide for management of acute promyelocytic leukemia: current evidence on its role in front-line therapy and recurrent disease","volume":"13","author":"Breccia","year":"2012","journal-title":"Expert Opin. Pharmacother."},{"key":"B13","doi-asserted-by":"publisher","first-page":"363","DOI":"10.3109\/10715760903555836","article-title":"Thiol redox systems and protein kinases in hepatic stellate cell regulatory processes","volume":"44","author":"Brunati","year":"2010","journal-title":"Free Radic. Res."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1295","DOI":"10.1016\/S1470-2045(15)00193-X","article-title":"Arsenic trioxide and all-trans retinoic acid treatment for acute promyelocytic leukaemia in all risk groups (AML17): results of a randomised, controlled, phase 3 trial","volume":"16","author":"Burnett","year":"2015","journal-title":"Lancet Oncol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"232","DOI":"10.3760\/cma.j.issn.1007-3418.2011.03.023","article-title":"The application of the anti-inflammatory and hepatoprotective drugs on drug-induced liver disease","volume":"19","author":"Chen","year":"2011","journal-title":"Chin. J. Hepatology"},{"key":"B16","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41423-022-00956-0","article-title":"Arsenic trioxide elicits prophylactic and therapeutic immune responses against solid tumors by inducing necroptosis and ferroptosis","volume":"20","author":"Chen","year":"2023","journal-title":"Cell Mol. Immunol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"6425","DOI":"10.1182\/blood-2010-11-283598","article-title":"From an old remedy to a magic bullet: molecular mechanisms underlying the therapeutic effects of arsenic in fighting leukemia","volume":"117","author":"Chen","year":"2011","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jnutbio.2016.09.001","article-title":"Pomegranate protects against arsenic-induced p53-dependent ROS-mediated inflammation and apoptosis in liver cells","volume":"38","author":"Choudhury","year":"2016","journal-title":"J. Nutr. Biochem."},{"key":"B19","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1021\/tx400441h","article-title":"Chemical mechanism of arsenic biomethylation","volume":"27","author":"Cullen","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"117607","DOI":"10.1016\/j.lfs.2020.117607","article-title":"Role of PML SUMOylation in arsenic trioxide-induced fibrosis in HSCs","volume":"251","author":"Dai","year":"2020","journal-title":"Life Sci."},{"key":"B21","doi-asserted-by":"publisher","first-page":"113924","DOI":"10.1016\/j.fct.2023.113924","article-title":"Hepatoprotective and anti-hyperglycemic effects of ferulic acid in arsenic-exposed mice","volume":"178","author":"Daryagasht","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1421438","DOI":"10.1155\/2018\/1421438","article-title":"Carnosic acid, a natural diterpene, attenuates arsenic-induced hepatotoxicity via reducing oxidative stress, MAPK activation, and apoptotic cell death pathway","volume":"2018","author":"Das","year":"2018","journal-title":"Oxid. Med. Cell Longev."},{"key":"B23","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1016\/S2468-1253(17)30266-2","article-title":"Risk stratification after paracetamol overdose using mechanistic biomarkers: results from two prospective cohort studies","volume":"3","author":"Dear","year":"2018","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1979","DOI":"10.1021\/tx500313k","article-title":"Pathway of human AS3MT arsenic methylation","volume":"27","author":"Dheeman","year":"2014","journal-title":"Chem. Res. Toxicol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1002\/tox.23324","article-title":"Imbalanced inflammatory response in subchronic arsenic-induced liver injury and the protective effects of Ginkgo biloba extract in rats: potential role of cytokines mediated cell-cell interactions","volume":"36","author":"Dong","year":"2021","journal-title":"Environ. Toxicol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s12011-019-01975-1","article-title":"Co-Exposure to arsenic-fluoride results in endoplasmic reticulum stress-induced apoptosis through the PERK signaling pathway in the liver of offspring rats","volume":"197","author":"Dong","year":"2020","journal-title":"Biol. Trace Elem. Res."},{"key":"B113","doi-asserted-by":"publisher","first-page":"2073","DOI":"10.1002\/tox.2332410","article-title":"Imbalanced inflammatory response in subchronic arsenic-induced liver injury and the protective effects of Ginkgo biloba extract in rats: potential role of cytokines mediated cell-cell interactions","volume":"39","author":"Dong","year":"2021","journal-title":"Environ. Toxicol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1007\/s00204-009-0499-7","article-title":"Metabolism of arsenic in human liver: the role of membrane transporters","volume":"84","author":"Drobn\u00e1","year":"2010","journal-title":"Archives Toxicol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"118965","DOI":"10.1016\/j.lfs.2020.118965","article-title":"Mechanisms involved in the possible protective effect of chrysin against sodium arsenite-induced liver toxicity in rats","volume":"267","author":"Fatemi","year":"2021","journal-title":"Life Sci."},{"key":"B29","doi-asserted-by":"publisher","first-page":"4180","DOI":"10.1007\/s12011-023-03968-7","article-title":"Arsenic-induced ferroptosis in chicken hepatocytes via the mitochondrial ROS pathway","volume":"202","author":"Gao","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"B30","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1016\/j.taap.2010.11.016","article-title":"Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice","volume":"251","author":"Ghatak","year":"2011","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1080\/10428194.2021.1978084","article-title":"The pharmacokinetics of therapeutic arsenic trioxide in acute promyelocytic leukemia patients","volume":"63","author":"Ghiuzeli","year":"2022","journal-title":"Leuk. Lymphoma"},{"key":"B32","doi-asserted-by":"publisher","first-page":"29989","DOI":"10.1074\/jbc.M109.090530","article-title":"Autophagy is a critical mechanism for the induction of the antileukemic effects of arsenic trioxide","volume":"285","author":"Goussetis","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s41419-021-03868-5","article-title":"Interactions between m6A modification and miRNAs in malignant tumors","volume":"12","author":"Han","year":"2021","journal-title":"Cell Death Dis."},{"key":"B34","doi-asserted-by":"publisher","first-page":"e67","DOI":"10.1097\/MPH.0b013e31827e91bc","article-title":"Hepatotoxicity from arsenic trioxide for pediatric acute promyelocytic leukemia","volume":"35","author":"Hao","year":"2013","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"B35","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1289\/ehp.1307545","article-title":"Chronic arsenic exposure and angiogenesis in human bronchial epithelial cells via the ROS\/miR-199a-5p\/HIF-1\u03b1\/COX-2 pathway","volume":"122","author":"He","year":"2014","journal-title":"Environ. Health Perspect."},{"key":"B36","doi-asserted-by":"publisher","first-page":"2587","DOI":"10.1007\/s00204-020-02772-9","article-title":"Biotransformation of arsenic and toxicological implication of arsenic metabolites","volume":"94","author":"Hirano","year":"2020","journal-title":"Arch. Toxicol."},{"key":"B37","doi-asserted-by":"publisher","first-page":"2806","DOI":"10.3390\/molecules27092806","article-title":"Dictyophora polysaccharide attenuates as-mediated PINK1\/parkin pathway-induced mitophagy in L-02 cell through scavenging ROS","volume":"27","author":"Hu","year":"2022","journal-title":"Molecules"},{"key":"B38","doi-asserted-by":"publisher","first-page":"79","DOI":"10.1016\/j.etap.2018.05.012","article-title":"The PKC\u03b4-Nrf2-ARE signalling pathway may be involved in oxidative stress in arsenic-induced liver damage in rats","volume":"62","author":"Hu","year":"2018","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B116","doi-asserted-by":"publisher","first-page":"1115","DOI":"10.1038\/cr.2017.999","article-title":"Ythdc2 is an N(6)-methyladenosine binding protein that regulates mammalian spermatogenesis","volume":"27","author":"Hsu","year":"2017","journal-title":"Cell Res"},{"key":"B39","doi-asserted-by":"publisher","first-page":"110","DOI":"10.3390\/toxics11020110","article-title":"Evaluation of the possible protective role of nobiletin against arsenic-induced liver damage in male albino rats","volume":"11","author":"Ijaz","year":"2023","journal-title":"Toxics"},{"key":"B40","doi-asserted-by":"publisher","first-page":"69","DOI":"10.3390\/molecules21010069","article-title":"Biochanin A ameliorates arsenic-induced hepatoand hematotoxicity in rats","volume":"21","author":"Jalaludeen","year":"2016","journal-title":"Molecules"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1913","DOI":"10.2146\/ajhp080342","article-title":"Arsenic trioxide as first-line treatment for acute promyelocytic leukemia","volume":"66","author":"Leu","year":"2009","journal-title":"Am. J. Health Syst. Pharm."},{"key":"B42","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1016\/j.canlet.2020.10.023","article-title":"MicroRNA-15b in extracellular vesicles from arsenite-treated macrophages promotes the progression of hepatocellular carcinomas by blocking the LATS1-mediated Hippo pathway","volume":"497","author":"Li","year":"2021","journal-title":"Cancer Lett."},{"key":"B43","doi-asserted-by":"publisher","first-page":"2306","DOI":"10.3892\/or.2020.7764","article-title":"Tannic acid attenuates hepatic oxidative stress, apoptosis and inflammation by activating the Keap1-Nrf2\/ARE signaling pathway in arsenic trioxide-toxicated rats","volume":"44","author":"Li","year":"2020","journal-title":"Oncol. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"315205","DOI":"10.1155\/2015\/315205","article-title":"Lutein has a protective effect on hepatotoxicity induced by arsenic via Nrf2 signaling","volume":"2015","author":"Li","year":"2015","journal-title":"Biomed. Res. Int."},{"key":"B45","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1038\/s41419-017-0018-3","article-title":"Arsenic trioxide promoting ETosis in acute promyelocytic leukemia through mTOR-regulated autophagy","volume":"9","author":"Li","year":"2018","journal-title":"Cell Death Dis."},{"key":"B46","first-page":"738","article-title":"Magnesium isoglycyrrhizinate used in the treatment of chemotherapeutic drugs-induced acute liver dysfunction: a phase III clinical trial","volume":"32","author":"Li-Na","year":"2012","journal-title":"Tumor"},{"key":"B47","doi-asserted-by":"publisher","first-page":"e3159","DOI":"10.1038\/cddis.2017.482","article-title":"Metformin ameliorates arsenic trioxide hepatotoxicity via inhibiting mitochondrial complex I","volume":"8","author":"Ling","year":"2017","journal-title":"Cell Death Dis."},{"key":"B48","doi-asserted-by":"publisher","first-page":"647687","DOI":"10.3389\/fphar.2021.647687","article-title":"Pharmacokinetic characteristics, tissue bioaccumulation and toxicity profiles of oral arsenic trioxide in rats: implications for the treatment and risk assessment of acute promyelocytic leukemia","volume":"12","author":"Liu","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"524","DOI":"10.3390\/molecules22040524","article-title":"Protective effect of bicyclol on anti-tuberculosis drug induced liver injury in rats","volume":"22","author":"Liu","year":"2017","journal-title":"Molecules"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.2147\/dddt.S247947","article-title":"Protective effects of crocetin on arsenic trioxide-induced hepatic injury: involvement of suppression in oxidative stress and inflammation through activation of Nrf2 signaling pathway in rats","volume":"14","author":"Liu","year":"2020","journal-title":"Drug Des. Devel Ther."},{"key":"B51","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1056\/NEJMoa1300874","article-title":"Retinoic acid and arsenic trioxide for acute promyelocytic leukemia","volume":"369","author":"Lo-Coco","year":"2013","journal-title":"N. Engl. J. Med."},{"key":"B52","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1007\/s00277-015-2477-x","article-title":"Evaluating frequency of PML-RARA mutations and conferring resistance to arsenic trioxide-based therapy in relapsed acute promyelocytic leukemia patients","volume":"94","author":"Lou","year":"2015","journal-title":"Ann. Hematol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"114687","DOI":"10.1016\/j.taap.2019.114687","article-title":"Influence of AS3MT polymorphisms on arsenic metabolism and liver injury in APL patients treated with arsenic trioxide","volume":"379","author":"Lu","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1016\/j.etap.2010.09.011","article-title":"Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by dietary phosphate","volume":"31","author":"Majumdar","year":"2011","journal-title":"Environ. Toxicol. Pharmacol."},{"key":"B55","doi-asserted-by":"publisher","first-page":"384","DOI":"10.1007\/s12072-023-10633-7","article-title":"Chinese guideline for the diagnosis and treatment of drug-induced liver injury: an update","volume":"18","author":"Mao","year":"2024","journal-title":"Hepatol. Int."},{"key":"B56","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1038\/sj.leu.2404165","article-title":"Hepatotoxicity profile of single agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia, its impact on clinical outcome and the effect of genetic polymorphisms on the incidence of hepatotoxicity","volume":"20","author":"Mathews","year":"2006","journal-title":"Leukemia"},{"key":"B57","doi-asserted-by":"publisher","first-page":"3866","DOI":"10.1200\/JCO.2010.28.5031","article-title":"Single-agent arsenic trioxide in the treatment of newly diagnosed acute promyelocytic leukemia: long-term follow-up data","volume":"28","author":"Mathews","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"B58","doi-asserted-by":"publisher","first-page":"1389024","DOI":"10.3389\/fphar.2024.1389024","article-title":"Phytochemical profiling and anticancer potential of gardenia latifolia extracts against arsenic trioxide induced liver fibrosis in rat model","volume":"15","author":"Mehboob","year":"2024","journal-title":"Front. Pharmacol."},{"key":"B59","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/j.etp.2010.08.002","article-title":"Hepatoprotective role and antioxidant capacity of selenium on arsenic-induced liver injury in rats","volume":"64","author":"Messarah","year":"2012","journal-title":"Exp. Toxicol. Pathol."},{"key":"B60","doi-asserted-by":"publisher","first-page":"124","DOI":"10.3109\/15376516.2013.869778","article-title":"Arsenic-induced hepatic mitochondrial toxicity in rats and its amelioration by diallyl trisulfide","volume":"24","author":"Miltonprabu","year":"2014","journal-title":"Toxicol. Mech. Methods"},{"key":"B61","doi-asserted-by":"publisher","first-page":"127154","DOI":"10.1016\/j.jtemb.2023.127154","article-title":"Diosmin exerts hepatoprotective and antihyperglycemic effects against sodium arsenite-induced toxicity through the modulation of oxidative stress and inflammation in mice","volume":"78","author":"Mirzaei","year":"2023","journal-title":"J. Trace Elem. Med. Biol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"643","DOI":"10.1515\/jbcpp-2016-0020","article-title":"Protection against arsenic-induced hematological and hepatic anomalies by supplementation of vitamin C and vitamin E in adult male rats","volume":"27","author":"Mondal","year":"2016","journal-title":"J. Basic Clin. Physiol. Pharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2857","DOI":"10.1039\/d2na00167e","article-title":"Morin encapsulated chitosan nanoparticles (MCNPs) ameliorate arsenic induced liver damage through improvement of the antioxidant system and prevention of apoptosis and inflammation in mice","volume":"4","author":"Mondal","year":"2022","journal-title":"Nanoscale Adv."},{"key":"B64","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1001\/archinte.167.16.1752","article-title":"Serious adverse drug events reported to the Food and Drug Administration, 1998-2005","volume":"167","author":"Moore","year":"2007","journal-title":"Arch. Intern Med."},{"key":"B65","doi-asserted-by":"publisher","first-page":"6886","DOI":"10.1182\/bloodadvances.2023010559","article-title":"Vitamin C and D supplementation in acute myeloid leukemia","volume":"7","author":"Mouchel","year":"2023","journal-title":"Blood Adv."},{"key":"B66","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.cbi.2015.04.006","article-title":"Ameliorative efficacy of tetrahydrocurcumin against arsenic induced oxidative damage, dyslipidemia and hepatic mitochondrial toxicity in rats","volume":"235","author":"Muthumani","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"B67","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1093\/toxsci\/kfs154","article-title":"Release of apoptotic cytochrome C from mitochondria by dimethylarsinous acid occurs through interaction with voltage-dependent anion channel in vitro","volume":"128","author":"Naranmandura","year":"","journal-title":"Toxicol. Sci."},{"key":"B68","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/j.taap.2012.02.017","article-title":"The endoplasmic reticulum is a target organelle for trivalent dimethylarsinic acid (DMAIII)-induced cytotoxicity","volume":"260","author":"Naranmandura","year":"","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1094","DOI":"10.1021\/tx200156k","article-title":"Mitochondria are the main target organelle for trivalent monomethylarsonous acid (MMA(III))-induced cytotoxicity","volume":"24","author":"Naranmandura","year":"2011","journal-title":"Chem. Res. Toxicol."},{"key":"B70","doi-asserted-by":"publisher","first-page":"105391","DOI":"10.1016\/j.pestbp.2023.105391","article-title":"Citicoline ameliorates arsenic-induced hepatotoxicity and diabetes in mice by overexpression of VAMP2, PPAR-\u03b3, As3MT, and SIRT3","volume":"192","author":"Nikravesh","year":"2023","journal-title":"Pestic. Biochem. Physiol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"114760","DOI":"10.1016\/j.taap.2019.114760","article-title":"Chemotherapeutic doses of arsenic trioxide delays hepatic regeneration by oxidative stress and hepatocyte apoptosis in partial hepatectomy rat","volume":"382","author":"Nithyananthan","year":"2019","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"3315","DOI":"10.1182\/blood.v94.10.3315.422k16_3315_3324","article-title":"Studies on treatment of acute promyelocytic leukemia with arsenic trioxide: remission induction, follow-up, and molecular monitoring in 11 newly diagnosed and 47 relapsed acute promyelocytic leukemia patients","volume":"94","author":"Niu","year":"1999","journal-title":"Blood"},{"key":"B73","doi-asserted-by":"publisher","first-page":"S132","DOI":"10.1016\/j.jhep.2005.11.027","article-title":"Hepatotoxicity of antiretrovirals: incidence, mechanisms and management","volume":"44","author":"N\u00fa\u00f1ez","year":"2006","journal-title":"J. Hepatol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1002\/tox.23966","article-title":"Selenium and zinc alleviate hepatotoxicity induced by heavy metal mixture (cadmium, mercury, lead and arsenic) via attenuation of inflammo-oxidant pathways","volume":"39","author":"Ozoani","year":"2024","journal-title":"Environ. Toxicol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1016\/j.taap.2007.09.020","article-title":"Dithiothreitol abrogates the effect of arsenic trioxide on normal rat liver mitochondria and human hepatocellular carcinoma cells","volume":"226","author":"Paul","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"B76","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.envint.2015.04.002","article-title":"Epimutagenesis: a prospective mechanism to remediate arsenic-induced toxicity","volume":"81","author":"Paul","year":"2015","journal-title":"Environ. Int."},{"key":"B77","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1289\/ehp.1001937","article-title":"Associations of plasma selenium with arsenic and genomic methylation of leukocyte DNA in Bangladesh","volume":"119","author":"Pilsner","year":"2011","journal-title":"Environ. Health Perspect."},{"key":"B78","doi-asserted-by":"publisher","first-page":"3751","DOI":"10.1182\/blood-2010-02-269621","article-title":"Arsenic trioxide improves event-free and overall survival for adults with acute promyelocytic leukemia: north American Leukemia Intergroup Study C9710","volume":"116","author":"Powell","year":"2010","journal-title":"Blood"},{"key":"B79","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s00244-018-0511-4","article-title":"The arsenic contamination of drinking and groundwaters in Bangladesh: featuring biogeochemical aspects and implications on public health","volume":"75","author":"Raessler","year":"2018","journal-title":"Arch. Environ. Contam. Toxicol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.cotox.2017.10.011","article-title":"Oxidative stress and acute hepatic injury","volume":"7","author":"Ramachandran","year":"2018","journal-title":"Curr. Opin. Toxicol."},{"key":"B81","doi-asserted-by":"publisher","first-page":"1080","DOI":"10.1007\/s12011-020-02222-8","article-title":"Effects of selenium on arsenic-induced liver lesions in broilers","volume":"199","author":"Ren","year":"2021","journal-title":"Biol. Trace Elem. Res."},{"key":"B82","doi-asserted-by":"publisher","first-page":"118438","DOI":"10.1016\/j.lfs.2020.118438","article-title":"An appraisal on molecular and biochemical signalling cascades during arsenic-induced hepatotoxicity","volume":"260","author":"Renu","year":"2020","journal-title":"Life Sci."},{"key":"B83","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1002\/tox.21940","article-title":"Effects of nanoparticle-encapsulated curcumin on arsenic-induced liver toxicity in rats","volume":"30","author":"Sankar","year":"2015","journal-title":"Environ. Toxicol."},{"key":"B84","doi-asserted-by":"publisher","first-page":"1546297","DOI":"10.1155\/2022\/1546297","article-title":"Arsenic-induced injury of mouse hepatocytes through lysosome and mitochondria: an in vitro study","volume":"2022","author":"Santra","year":"2022","journal-title":"Int. J. Hepatol."},{"key":"B85","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1081\/clt-100100949","article-title":"Hepatic damage caused by chronic arsenic toxicity in experimental animals","volume":"38","author":"Santra","year":"2000","journal-title":"J. Toxicol. Clin. Toxicol."},{"key":"B86","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1177\/0748233710365694","article-title":"Ascorbic acid improves mitochondrial function in liver of arsenic-treated rat","volume":"26","author":"Singh","year":"2010","journal-title":"Toxicol. Ind. Health"},{"key":"B87","doi-asserted-by":"publisher","first-page":"1157","DOI":"10.1007\/s00204-013-1034-4","article-title":"Oxidative stress: the mitochondria-dependent and mitochondria-independent pathways of apoptosis","volume":"87","author":"Sinha","year":"2013","journal-title":"Arch. Toxicol."},{"key":"B88","doi-asserted-by":"publisher","first-page":"108561","DOI":"10.1016\/j.envres.2019.108561","article-title":"Food as medicine: selenium enriched lentils offer relief against chronic arsenic poisoning in Bangladesh","volume":"176","author":"Smits","year":"2019","journal-title":"Environ. Res."},{"key":"B89","first-page":"104","article-title":"Hydroxytyrosol improving metabolic response by amelioration of oxidative stress following arsenic exposure in rat liver","volume":"15","author":"Soni","year":"2020","journal-title":"Res. J. Biotechnol."},{"key":"B90","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1111\/bjh.16151","article-title":"Differentiation syndrome in acute promyelocytic leukaemia","volume":"187","author":"Stahl","year":"2019","journal-title":"Br. J. Haematol."},{"key":"B91","doi-asserted-by":"publisher","first-page":"2231738","DOI":"10.1080\/16078454.2023.2231738","article-title":"Sulfhydryl compound levels are associated with ATO-induced side effects in acute promyelocytic leukemia patients","volume":"28","author":"Sui","year":"2023","journal-title":"Hematology"},{"key":"B92","doi-asserted-by":"publisher","first-page":"1380","DOI":"10.1038\/ajg.2012.138","article-title":"A prospective nationwide study of drug-induced liver injury in Korea","volume":"107","author":"Suk","year":"2012","journal-title":"Am. J. Gastroenterol."},{"key":"B93","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1111\/liv.15290","article-title":"Efficacy and safety of bicyclol for treating patients with idiosyncratic acute drug-induced liver injury: a multicenter, randomized, phase II trial","volume":"42","author":"Tang","year":"2022","journal-title":"Liver Int."},{"key":"B94","doi-asserted-by":"publisher","first-page":"1203","DOI":"10.33594\/000000082","article-title":"Sulforaphane potentially ameliorates arsenic induced hepatotoxicity in albino Wistar rats: implication of PI3K\/Akt\/Nrf2 signaling pathway","volume":"52","author":"Thangapandiyan","year":"2019","journal-title":"Cell Physiol. Biochem."},{"key":"B95","doi-asserted-by":"publisher","first-page":"684","DOI":"10.1080\/01635581.2018.1460676","article-title":"L-ascorbic acid and \u03b1-tocopherol reduces hepatotoxicity associated with arsenic trioxide chemotherapy by modulating Nrf2 and Bcl2 transcription factors in chang liver cells","volume":"70","author":"Vineetha","year":"2018","journal-title":"Nutr. Cancer"},{"key":"B96","doi-asserted-by":"publisher","first-page":"1170","DOI":"10.1016\/j.leukres.2011.06.002","article-title":"The efficacy and safety of arsenic trioxide with or without all-trans retinoic acid for the treatment of acute promyelocytic leukemia: a meta-analysis","volume":"35","author":"Wang","year":"2011","journal-title":"Leuk. Res."},{"key":"B97","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1038\/s41408-022-00753-y","article-title":"An effective and chemotherapy-free strategy of all-trans retinoic acid and arsenic trioxide for acute promyelocytic leukemia in all risk groups (APL15 trial)","volume":"12","author":"Wang","year":"2022","journal-title":"Blood Cancer J."},{"key":"B98","doi-asserted-by":"publisher","first-page":"5083","DOI":"10.1007\/s12011-023-03584-5","article-title":"Reduced peripheral blood mitochondrial DNA copy number as identification biomarker of suspected arsenic-induced liver damage","volume":"201","author":"Wang","year":"2023","journal-title":"Biol. Trace Elem. Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"2102","DOI":"10.1111\/liv.14204","article-title":"Efficacy and safety of magnesium isoglycyrrhizinate injection in patients with acute drug-induced liver injury: a phase II trial","volume":"39","author":"Wang","year":"2019","journal-title":"Liver Int."},{"key":"B115","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.stem.2017.11.0162","article-title":"METTL14 inhibits hematopoietic stem\/progenitor differentiation and promotes leukemogenesis via mRNA m(6)A modification","volume":"22","author":"Weng","year":"2018","journal-title":"Cell Stem Cell"},{"key":"B100","doi-asserted-by":"publisher","first-page":"130276","DOI":"10.1016\/j.jhazmat.2022.130276","article-title":"The lncRNA HOTAIR via miR-17-5p is involved in arsenite-induced hepatic fibrosis through regulation of Th17 cell differentiation","volume":"443","author":"Wu","year":"2023","journal-title":"J. Hazard Mater"},{"key":"B101","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1007\/s12011-016-0810-4","article-title":"Oxidative damage induced by arsenic in mice or rats: a systematic review and meta-analysis","volume":"176","author":"Xu","year":"2017","journal-title":"Biol. Trace Elem. Res."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1197","DOI":"10.1002\/tox.24008","article-title":"Assessing the mechanisms and adjunctive therapy for arsenic-induced liver injury in rats","volume":"39","author":"Xu","year":"2024","journal-title":"Environ. Toxicol."},{"key":"B103","doi-asserted-by":"publisher","first-page":"6025","DOI":"10.1002\/jcp.30288","article-title":"miR-21-regulated M2 polarization of macrophage is involved in arsenicosis-induced hepatic fibrosis through the activation of hepatic stellate cells","volume":"236","author":"Xue","year":"2021","journal-title":"J. Cell Physiol."},{"key":"B114","doi-asserted-by":"publisher","first-page":"1062","DOI":"10.1038\/s41422-018-0097-411","article-title":"A dynamic N6-methyladenosine methylome regulates intrinsic and acquired resistance to tyrosine kinase inhibitors","volume":"28","author":"Yan","year":"2021","journal-title":"Cell Res."},{"key":"B104","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s12011-016-0821-1","article-title":"Activation of the Nrf2 signaling pathway involving KLF9 plays a critical role in allicin resisting against arsenic trioxide-induced hepatotoxicity in rats","volume":"176","author":"Yang","year":"","journal-title":"Biol. Trace Elem. Res."},{"key":"B105","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1007\/s12011-016-0821-1","article-title":"Activation of the Nrf2 signaling pathway involving KLF9 plays a critical role in allicin resisting against arsenic trioxide-induced hepatotoxicity in rats","volume":"176","author":"Yang","year":"","journal-title":"Biol. Trace Elem. Res."},{"key":"B106","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1016\/j.cell.2013.12.010","article-title":"Regulation of ferroptotic cancer cell death by GPX4","volume":"156","author":"Yang","year":"2014","journal-title":"Cell"},{"key":"B107","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1080\/15376516.2017.1368054","article-title":"The mechanism of protective effect of crocin against liver mitochondrial toxicity caused by arsenic III","volume":"28","author":"Yousefsani","year":"2018","journal-title":"Toxicol. Mech. Methods"},{"key":"B108","doi-asserted-by":"publisher","first-page":"1340","DOI":"10.1177\/10781552211024727","article-title":"Arsenic trioxide dose capping to decrease toxicity in the treatment of acute promyelocytic leukemia","volume":"28","author":"Zacholski","year":"2022","journal-title":"J. Oncol. Pharm. Pract."},{"key":"B109","doi-asserted-by":"publisher","first-page":"3773","DOI":"10.18632\/oncotarget.13931","article-title":"Melatonin protects against arsenic trioxide-induced liver injury by the upregulation of Nrf2 expression through the activation of PI3K\/AKT pathway","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"B110","doi-asserted-by":"publisher","first-page":"122","DOI":"10.1007\/s12011-023-03676-21","article-title":"Clinical indicators of hepatotoxicity in newly diagnosed acute promyelocytic leukemia patients undergoing arsenic trioxide treatment","volume":"202","author":"Zhang","year":"2024","journal-title":"Biol. Trace Elem. Res."},{"key":"B111","doi-asserted-by":"publisher","first-page":"617202","DOI":"10.1155\/2014\/617202","article-title":"Resveratrol, a natural antioxidant, has a protective effect on liver injury induced by inorganic arsenic exposure","volume":"2014","author":"Zhang","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"B112","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1186\/s40164-021-00205-6","article-title":"Importance of monitoring arsenic methylation metabolism in acute promyelocytic leukemia patients receiving the treatment of arsenic trioxide","volume":"10","author":"Zheng","year":"2021","journal-title":"Exp. Hematol. Oncol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1536388\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T06:39:49Z","timestamp":1740033589000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1536388\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":116,"alternative-id":["10.3389\/fphar.2025.1536388"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1536388","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]},"article-number":"1536388"}}