{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,7]],"date-time":"2025-10-07T01:13:26Z","timestamp":1759799606200,"version":"build-2065373602"},"reference-count":55,"publisher":"Georg Thieme Verlag KG","issue":"08","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We investigated, in vivo, the chemopreventive efficacy of sinapic acid, as a\n                        known radical scavenger and antioxidant on mortality and toxicity in a\n                        N-ethyl-N-nitrosourea (ENU)-induced chronic lymphocytic leukemia (CLL) model\n                        in mice.<\/jats:p><jats:p>Mice were divided into three groups: control (normal saline), ENU (80\u2009mg\/kg,\n                        i.p., single dose on day 31), and sinapic acid+ENU (pretreated with 30\u2009mg\/kg\n                        of sinapic acid, i.p., daily for 30 days, followed by 80\u2009mg\/kg of ENU). Body\n                        weight changes and mortality were monitored over 120 days. After this\n                        period, the animals were sacrificed, and lymphocytes, the target cells in\n                        CLL, were isolated and evaluated for various cellular parameters.<\/jats:p><jats:p>Sinapic acid significantly (P&lt;0.001) increased mouse survival up to 71%,\n                        delayed time of death, and prevented weight loss following ENU exposure.\n                        Additionally, sinapic acid inhibited the formation of reactive oxygen\n                        species (ROS) (P&lt;0.001), lysosomal and mitochondrial dysfunction\n                        (P&lt;0.001), and lipid peroxidation (P&lt;0.05) in the isolated\n                        lymphocytes. These findings indicate a protective effect of sinapic acid\n                        against ENU-induced lethal toxicity.<\/jats:p><jats:p>This study confirms that sinapic acid may serve as a promising\n                        chemopreventive agent against carcinogenicity induced by alkylating agents,\n                        primarily through the inhibition of oxidative stress and\n                        lysosomal\/mitochondrial dysfunction.<\/jats:p>","DOI":"10.1055\/a-2687-0870","type":"journal-article","created":{"date-parts":[[2025,9,8]],"date-time":"2025-09-08T22:47:00Z","timestamp":1757371620000},"page":"334-342","source":"Crossref","is-referenced-by-count":0,"title":["Sinapic Acid Protects Mortality and Toxicity Induced by\n                    N-Ethyl-N-Nitrosourea, a Full Carcinogen Agent, in Mice"],"prefix":"10.1055","volume":"75","author":[{"given":"Ahmad","family":"Salimi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil\n                    University of Medical Sciences, Ardabil, Iran"},{"name":"Traditional Medicine and Hydrotherapy Research Center, Ardabil\n                    University of Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahshad","family":"Pourgholi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil\n                    University of Medical Sciences, Ardabil, Iran"},{"name":"Students Research Committee, Faculty of Pharmacy, Ardabil University of\n                    Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saleh","family":"Khezri","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil\n                    University of Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shadi","family":"Haddadi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil\n                    University of Medical Sciences, Ardabil, Iran"},{"name":"Students Research Committee, Faculty of Pharmacy, Ardabil University of\n                    Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bahare","family":"Asgari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, School of Pharmacy, Ardabil\n                    University of Medical Sciences, Ardabil, Iran"},{"name":"Students Research Committee, Faculty of Pharmacy, Ardabil University of\n                    Medical Sciences, Ardabil, Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,9,8]]},"reference":[{"key":"ref1","first-page":"e00053","article-title":"Carcinogenic effects of nitrosodimethylamine (NDMA) contamination in ranitidine:\n                    defining the relationship with renal malignancies","volume":"1","author":"S A Gold","year":"2023","journal-title":"JU Open Plus"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1002\/mpo.1126","article-title":"Therapy-related leukemia associated with alkylating agents","volume":"36","author":"S M Davies","year":"2001","journal-title":"Medical and Pediatric Oncology: The Official Journal of\n                    SIOP\u2014International Society of Pediatric Oncology (Societ\u00e9 Internationale\n                    d\u2019Oncologie P\u00e9diatrique"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"456","DOI":"10.1016\/B978-1-4377-1015-1.00044-8","article-title":"44 - Secondary cancers in cancer survivors. Supportive Oncology","author":"D L Friedman","year":"2011","journal-title":"Saint Louis: W.B. Saunders"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"101070","DOI":"10.1016\/j.blre.2023.101070","article-title":"\u2018Secondary\u2019acute lymphoblastic\/lymphocytic leukemia-done playing second\n                    fiddle?","author":"YJR A Riazat-Kesh","year":"2023","journal-title":"Blood Reviews"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1080\/10428190701769657","article-title":"Influence of DNA damage and repair upon the risk of treatment related\n                    leukemia","volume":"49","author":"V Guillem","year":"2008","journal-title":"Leukemia & lymphoma"},{"key":"ref6","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1177\/1947601911408076","article-title":"Genetic abnormalities and challenges in the treatment of acute myeloid\n                    leukemia","volume":"2","author":"C C Kumar","year":"2011","journal-title":"Genes & cancer"},{"key":"ref7","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.cbi.2009.11.025","article-title":"Cytogenetic and genetic pathways in therapy-related acute myeloid leukemia","volume":"184","author":"Z Qian","year":"2010","journal-title":"Chemico-biological interactions"},{"key":"ref8","doi-asserted-by":"publisher","first-page":"e2011069","DOI":"10.4084\/mjhid.2011.069","article-title":"Incidence of acute myeloid leukemia after breast cancer","volume":"3","author":"C G Valentini","year":"2011","journal-title":"Mediterranean journal of hematology and infectious\n                    diseases"},{"key":"ref9","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1186\/1745-6673-8-14","article-title":"Work-related leukemia: a systematic review","volume":"8","author":"I Polychronakis","year":"2013","journal-title":"Journal of occupational medicine and toxicology (London,\n                    England)"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"2584","DOI":"10.3109\/10428194.2014.894189","article-title":"Acute myeloid leukemia risk by industry and occupation","volume":"55","author":"R J Tsai","year":"2014","journal-title":"Leuk Lymphoma"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"zcad015","DOI":"10.1093\/narcan\/zcad015","article-title":"Molecular origins of mutational spectra produced by the environmental carcinogen\n                    N-nitrosodimethylamine and SN1 chemotherapeutic agents","volume":"5","author":"A L Armijo","year":"2023","journal-title":"NAR cancer"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"e23067","DOI":"10.1002\/jbt.23067","article-title":"A review of the mutagenic potential of N-ethyl-N-nitrosourea (ENU) to induce\n                    hematological malignancies","volume":"36","author":"P Nath","year":"2022","journal-title":"Journal of Biochemical and Molecular Toxicology"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12940-019-0525-z","article-title":"Impact of high drinking water nitrate levels on the endogenous formation of\n                    apparent N-nitroso compounds in combination with meat intake in healthy\n                    volunteers","volume":"18","author":"S G van Breda","year":"2019","journal-title":"Environmental Health"},{"key":"ref14","first-page":"e07884","article-title":"Risk assessment of N-nitrosamines in food","volume":"21","author":"D Schrenk","year":"2023","journal-title":"EFSA Journal"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1007\/s10552-005-0168-y","article-title":"A review: dietary and endogenously formed N-nitroso compounds and risk of\n                    childhood brain tumors","volume":"16","author":"M Dietrich","year":"2005","journal-title":"Cancer Causes & Control"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"503669","DOI":"10.1016\/j.mrgentox.2023.503669","article-title":"Adopting duplex sequencing technology for genetic toxicity testing: A\n                    proof-of-concept mutagenesis experiment with N-ethyl-N-nitrosourea (ENU)-exposed\n                    rats","volume":"891","author":"S L Smith-Roe","year":"2023","journal-title":"Mutation Research\/Genetic Toxicology and Environmental\n                    Mutagenesis"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1053\/j.seminoncol.2008.04.012","article-title":"Therapy-related myeloid leukemia","volume":"35","author":"L A Godley","year":"2008","journal-title":"Seminars in oncology"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"87","DOI":"10.2174\/1568009622666220816120353","article-title":"Characteristic Hallmarks of Aging and the Impact on Carcinogenesis","volume":"23","author":"S Terracina","year":"2023","journal-title":"Current Cancer Drug Targets"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"809308","DOI":"10.3389\/fphar.2021.809308","article-title":"Cancer Chemoprevention: A Strategic Approach Using Phytochemicals","volume":"12","author":"M Swetha","year":"2021","journal-title":"Frontiers in pharmacology"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"113384","DOI":"10.1016\/j.biopha.2022.113384","article-title":"Plant-derived bioactive compounds in colon cancer treatment: An updated\n                    review","volume":"153","author":"E Esmeeta","year":"2022","journal-title":"Biomedicine & Pharmacotherapy"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines10081948","article-title":"Plant-Derived Bioactive Compounds in Colorectal Cancer: Insights from Combined\n                    Regimens with Conventional Chemotherapy to Overcome Drug-Resistance","volume":"10","author":"L I Gavrilas","year":"2022","journal-title":"Biomedicines"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3390\/biom9110735","article-title":"Role of Reactive Oxygen Species in Cancer Progression: Molecular Mechanisms and\n                    Recent Advancements","volume":"9","author":"V Aggarwal","year":"2019","journal-title":"Biomolecules"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1111\/1541-4337.12041","article-title":"Sinapic acid and its derivatives: natural sources and bioactivity","volume":"13","author":"N Ni\u0107iforovi\u0107","year":"2014","journal-title":"Comprehensive reviews in food science and food safety"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"3571614","DOI":"10.1155\/2016\/3571614","article-title":"Sinapic Acid and Its Derivatives as Medicine in Oxidative Stress-Induced\n                    Diseases and Aging","volume":"2016","author":"C Chen","year":"2016","journal-title":"Oxidative medicine and cellular longevity"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2023.122390","article-title":"Chronic inflammation and cancer; the two sides of a coin","author":"Q Fernandes","year":"2023","journal-title":"Life Sciences"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s42269-022-00943-5","article-title":"Mechanisms involved in the anticancer effects of sinapic acid","volume":"46","author":"A Pandi","year":"2022","journal-title":"Bulletin of the National Research Centre"},{"key":"ref27","first-page":"1","article-title":"Histopathological and genetic changes proved the anti-cancer potential of free\n                    and nano-capsulated sinapic acid","volume":"62","author":"D A Badr","year":"2019","journal-title":"Applied Biological Chemistry"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1253","DOI":"10.1177\/0960327114522501","article-title":"Chemopreventive effect of sinapic acid on 1,2-dimethylhydrazine-induced\n                    experimental rat colon carcinogenesis","volume":"33","author":"C Balaji","year":"2014","journal-title":"Human & experimental toxicology"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"7125","DOI":"10.1016\/j.sjbs.2021.08.001","article-title":"Lung cancer induced by Benzo (A) Pyrene: ChemoProtective effect of sinapic acid\n                    in swiss albino mice","volume":"28","author":"X Hu","year":"2021","journal-title":"Saudi journal of biological sciences"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"678","DOI":"10.3390\/cancers12030678","article-title":"N-Ethyl-n-Nitrosourea induced Leukaemia in a mouse model through upregulation of\n                    vascular endothelial growth factor and evading apoptosis","volume":"12","author":"A Aliyu","year":"2020","journal-title":"Cancers"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.cbi.2011.08.004","article-title":"Protective role of sinapic acid against arsenic \u2013 Induced toxicity in rats","volume":"194","author":"L Pari","year":"2011","journal-title":"Chemico-biological interactions"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"e115682","DOI":"10.1371\/journal.pone.0115682","article-title":"Sinapic acid prevents hypertension and cardiovascular remodeling in\n                    pharmacological model of nitric oxide inhibited rats","volume":"9","author":"T Silambarasan","year":"2014","journal-title":"PloS one"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jenvrad.2019.03.009","article-title":"Mitochondrial protective and antioxidant agents protect toxicity induced by\n                    depleted uranium in isolated human lymphocytes","volume":"203","author":"M Soltani","year":"2019","journal-title":"Journal of environmental radioactivity"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1080\/07357907.2016.1276187","article-title":"Chrysin as an anti-cancer agent exerts selective toxicity by directly inhibiting\n                    mitochondrial complex II and V in CLL B-lymphocytes","volume":"35","author":"A Salimi","year":"2017","journal-title":"Cancer investigation"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1080\/01635581.2016.1235717","article-title":"Selective anticancer activity of acacetin against chronic lymphocytic leukemia\n                    using both in vivo and in vitro methods: key role of oxidative stress and\n                    cancerous mitochondria","volume":"68","author":"A Salimi","year":"2016","journal-title":"Nutrition and cancer"},{"key":"ref36","first-page":"555","article-title":"Matrine induction of ROS mediated apoptosis in human ALL B-lymphocytes via\n                    mitochondrial targeting","volume":"19","author":"M Aghvami","year":"2018","journal-title":"Asian Pacific journal of cancer prevention: APJCP"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"233","DOI":"10.5487\/TR.2017.33.3.233","article-title":"Xylene induces oxidative stress and mitochondria damage in isolated human\n                    lymphocytes","volume":"33","author":"A Salimi","year":"2017","journal-title":"Toxicological research"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1016\/0003-9861(59)90090-6","article-title":"Tissue sulfhydryl groups","volume":"82","author":"G L Ellman","year":"1959","journal-title":"Archives of biochemistry and biophysics"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"2499","DOI":"10.3892\/mmr.2016.4819","article-title":"Effect of glutamate on lysosomal membrane permeabilization in primary cultured\n                    cortical neurons","volume":"13","author":"M Yan","year":"2016","journal-title":"Molecular Medicine Reports"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/S0005-2728(03)00110-5","article-title":"Rhodamine 123 as a probe of mitochondrial membrane potential: evaluation of\n                    proton flux through F0 during ATP synthesis","volume":"1606","author":"A Baracca","year":"2003","journal-title":"Biochimica et biophysica acta (BBA)-bioenergetics"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.3390\/ijerph9072444","article-title":"Secondary leukemia associated with the anti-cancer agent, etoposide, a\n                    topoisomerase II inhibitor","volume":"9","author":"S Ezoe","year":"2012","journal-title":"International journal of environmental research and public\n                    health"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"809308","DOI":"10.3389\/fphar.2021.809308","article-title":"Cancer chemoprevention: A strategic approach using phytochemicals","volume":"12","author":"M Swetha","year":"2022","journal-title":"Frontiers in pharmacology"},{"key":"ref43","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13092256","article-title":"Etiology of Acute Leukemia: A Review","volume":"13","author":"C K Tebbi","year":"2021","journal-title":"Cancers (Basel)"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3390\/sci4020015","article-title":"Apoptosis and pharmacological therapies for targeting thereof for cancer\n                    therapeutics","volume":"4","author":"V Singh","year":"2022","journal-title":"Sci"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13578-020-00489-x","article-title":"The role of lysosomes in cancer development and progression","volume":"10","author":"T Tang","year":"2020","journal-title":"Cell & bioscience"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13046-014-0106-5","article-title":"Dual effect of oxidative stress on leukemia cancer induction and treatment","volume":"33","author":"U K Udensi","year":"2014","journal-title":"Journal of Experimental & Clinical Cancer\n                    Research"},{"key":"ref47","doi-asserted-by":"publisher","DOI":"10.3390\/antiox9111156","article-title":"Redox Potential of Antioxidants in Cancer Progression and Prevention","volume":"9","author":"S George","year":"2020","journal-title":"Antioxidants (Basel, Switzerland)"},{"key":"ref48","first-page":"1","article-title":"Cytoprotective effects of sinapic acid on human keratinocytes (HaCaT) against\n                    ultraviolet B","volume":"2","author":"G R Kim","year":"2018","journal-title":"Biomedical Dermatology"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1139\/gen-2019-0151","article-title":"Insertions of mitochondrial DNA into the nucleus\u2014effects and role in cell\n                    evolution","volume":"63","author":"M J Puertas","year":"2020","journal-title":"Genome"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1177\/1535370216641787","article-title":"Role of mitochondrial dysfunction in cancer progression","volume":"241","author":"C-C Hsu","year":"2016","journal-title":"Experimental Biology and Medicine"},{"key":"ref51","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1002\/jbmr.3624","article-title":"An N-Ethyl-N-Nitrosourea (ENU)-Induced Tyr265Stop Mutation of the DNA Polymerase\n                    Accessory Subunit Gamma 2 (Polg2) Is Associated With Renal Calcification in\n                    Mice","volume":"34","author":"C M Gorvin","year":"2019","journal-title":"Journal of bone and mineral research : the official journal of the\n                    American Society for Bone and Mineral Research"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"669379","DOI":"10.3389\/fcell.2021.669379","article-title":"The mitochondrial response to DNA damage","volume":"9","author":"Z Rong","year":"2021","journal-title":"Frontiers in Cell and Developmental Biology"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"101554","DOI":"10.1016\/j.redox.2020.101554","article-title":"Sinapine, but not sinapic acid, counteracts mitochondrial oxidative stress in\n                    cardiomyocytes","volume":"34","author":"D Boulghobra","year":"2020","journal-title":"Redox Biology"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"3733","DOI":"10.1007\/s11033-021-06367-0","article-title":"Pharmacological and therapeutic applications of Sinapic acid\u2014An updated\n                    review","volume":"48","author":"A Pandi","year":"2021","journal-title":"Molecular Biology Reports"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"3984","DOI":"10.1016\/j.fct.2012.08.017","article-title":"Protective effects of sinapic acid on lysosomal dysfunction in isoproterenol\n                    induced myocardial infarcted rats","volume":"50","author":"S J Roy","year":"2012","journal-title":"Food and Chemical Toxicology"}],"container-title":["Drug Research"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2687-0870.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,6]],"date-time":"2025-10-06T22:40:38Z","timestamp":1759790438000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2687-0870"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,8]]},"references-count":55,"journal-issue":{"issue":"08","published-online":{"date-parts":[[2025,10,6]]},"published-print":{"date-parts":[[2025,10]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2687-0870","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["2194-9379","2194-9387"],"issn-type":[{"type":"print","value":"2194-9379"},{"type":"electronic","value":"2194-9387"}],"subject":[],"published":{"date-parts":[[2025,9,8]]}}}