{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T21:11:15Z","timestamp":1785618675553,"version":"3.56.0"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2025,2,1]],"date-time":"2025-02-01T00:00:00Z","timestamp":1738368000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100017649","name":"Hong Kong Government","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100017649","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012479","name":"General Research Fund of Shanghai Normal University","doi-asserted-by":"publisher","award":["HKU 17113120"],"award-info":[{"award-number":["HKU 17113120"]}],"id":[{"id":"10.13039\/501100012479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012479","name":"General Research Fund of Shanghai Normal University","doi-asserted-by":"publisher","award":["HKU 17127718"],"award-info":[{"award-number":["HKU 17127718"]}],"id":[{"id":"10.13039\/501100012479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012479","name":"General Research Fund of Shanghai Normal University","doi-asserted-by":"publisher","award":["HLCA\/M-703\/22"],"award-info":[{"award-number":["HLCA\/M-703\/22"]}],"id":[{"id":"10.13039\/501100012479","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002920","name":"Research Grants Council, University Grants Committee","doi-asserted-by":"publisher","award":["2020\/21"],"award-info":[{"award-number":["2020\/21"]}],"id":[{"id":"10.13039\/501100002920","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Food and Chemical Toxicology"],"published-print":{"date-parts":[[2025,2]]},"DOI":"10.1016\/j.fct.2024.115195","type":"journal-article","created":{"date-parts":[[2024,12,10]],"date-time":"2024-12-10T12:12:21Z","timestamp":1733832741000},"page":"115195","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":4,"special_numbering":"C","title":["Preclinical toxicity evaluation of the novel anti-hypertensive compound KSD179019"],"prefix":"10.1016","volume":"196","author":[{"given":"Shaik Abdullah","family":"Nawabjan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kailash","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1455-4357","authenticated-orcid":false,"given":"Muthu Iswarya","family":"G S","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rex K.H.","family":"Au-Yeung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengwei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6700-4346","authenticated-orcid":false,"given":"Hani","family":"El-Nezami","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Billy K.C.","family":"Chow","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"12","key":"10.1016\/j.fct.2024.115195_bib1","doi-asserted-by":"crossref","first-page":"e5646","DOI":"10.1590\/1414-431x20165646","article-title":"Non-clinical studies in the process of new drug development - Part II: good laboratory practice, metabolism, pharmacokinetics, safety and dose translation to clinical studies","volume":"49","author":"Andrade","year":"2016","journal-title":"Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas"},{"issue":"5","key":"10.1016\/j.fct.2024.115195_bib2","doi-asserted-by":"crossref","first-page":"F852","DOI":"10.1152\/ajprenal.00191.2015","article-title":"Secretin, at the hub of water-salt homeostasis","volume":"312","author":"Bai","year":"2017","journal-title":"Am. J. Physiol. Ren. Physiol."},{"key":"10.1016\/j.fct.2024.115195_bib3","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.jep.2014.09.013","article-title":"Toxicological evaluation of hydroethanolic extract of Helicteres sacarolha A. St.- Hil. et al","volume":"157","author":"Balogun","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.fct.2024.115195_bib4","doi-asserted-by":"crossref","DOI":"10.1016\/j.fct.2022.113562","article-title":"Mutagenic potential and structural alerts of phytotoxins","volume":"173","author":"Bassan","year":"2023","journal-title":"Food Chem. Toxicol."},{"key":"10.1016\/j.fct.2024.115195_bib5","doi-asserted-by":"crossref","DOI":"10.1016\/j.yrtph.2020.104843","article-title":"A cross-industry collaboration to assess if acute oral toxicity (Q)SAR models are fit-for-purpose for GHS classification and labelling","volume":"120","author":"Bercu","year":"2021","journal-title":"Regul. Toxicol. Pharmacol."},{"issue":"4","key":"10.1016\/j.fct.2024.115195_bib6","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s00424-024-02906-3","article-title":"Secretin: a hormone for HCO3\u2212 homeostasis","volume":"476","author":"Berg","year":"2024","journal-title":"Pflueg. Arch. Eur. J. Physiol."},{"issue":"3","key":"10.1016\/j.fct.2024.115195_bib7","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s43152-024-00056-3","article-title":"Cellular and molecular mechanisms of insulin resistance","volume":"5","author":"Chandrasekaran","year":"2024","journal-title":"Current Tissue Microenvironment Reports"},{"issue":"9","key":"10.1016\/j.fct.2024.115195_bib8","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0162953","article-title":"Difference in Leukocyte composition between women before and after menopausal age, and distinct sexual dimorphism","volume":"11","author":"Chen","year":"2016","journal-title":"PLoS One"},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib9","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1016\/j.drudis.2021.08.010","article-title":"Can preclinical drug development help to predict adverse events in clinical trials?","volume":"27","author":"Chi","year":"2022","journal-title":"Drug Discov. Today"},{"issue":"2","key":"10.1016\/j.fct.2024.115195_bib10","doi-asserted-by":"crossref","first-page":"83","DOI":"10.22506\/ti\/2015\/v22\/i2\/137667","article-title":"An approach to acute, subacute, subchronic, and chronic toxicity assessment in animal models","volume":"22","author":"Chinedu","year":"2015","journal-title":"Toxicol. Int."},{"issue":"5","key":"10.1016\/j.fct.2024.115195_bib11","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1016\/j.mpaic.2024.03.004","article-title":"Renal physiology: acid\u2013base balance","volume":"25","author":"Clayton-Smith","year":"2024","journal-title":"Anaesth. Intensive Care Med."},{"issue":"2","key":"10.1016\/j.fct.2024.115195_bib12","doi-asserted-by":"crossref","first-page":"E191","DOI":"10.1152\/ajpendo.00405.2020","article-title":"Bilirubin as a metabolic hormone: the physiological relevance of low levels","volume":"320","author":"Creeden","year":"2021","journal-title":"Am. J. Physiol. Endocrinol. Metabol."},{"key":"10.1016\/j.fct.2024.115195_bib13","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.bcp.2015.09.005","article-title":"SGLT2 inhibitors","volume":"101","author":"Dardi","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.fct.2024.115195_bib14","series-title":"A Comprehensive Guide to Toxicology in Nonclinical Drug Development","first-page":"109","article-title":"Acute, subacute, subchronic, and chronic general toxicity testing for preclinical drug development","author":"Denny","year":"2016"},{"issue":"10","key":"10.1016\/j.fct.2024.115195_bib15","doi-asserted-by":"crossref","first-page":"1171","DOI":"10.1038\/ng.3667","article-title":"The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals","volume":"48","author":"Ehret","year":"2016","journal-title":"Nat. Genet."},{"key":"10.1016\/j.fct.2024.115195_bib16","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.jep.2017.07.029","article-title":"Acute and sub-chronic toxicity studies of the aqueous extract from leaves of Cistus ladaniferus L. in mice and rats","volume":"209","author":"El Kabbaoui","year":"2017","journal-title":"J. Ethnopharmacol."},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib17","doi-asserted-by":"crossref","first-page":"5","DOI":"10.2478\/intox-2018-0001","article-title":"Advances in acute toxicity testing: strengths, weaknesses and regulatory acceptance","volume":"11","author":"Erhirhie","year":"2018","journal-title":"Interdiscipl. Toxicol."},{"issue":"3","key":"10.1016\/j.fct.2024.115195_bib18","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/j.jep.2013.12.034","article-title":"Acute and sub-chronic toxicity profile of methanol leaf extract of Gouania longipetala in rats","volume":"151","author":"Ezeja","year":"2014","journal-title":"J. Ethnopharmacol."},{"key":"10.1016\/j.fct.2024.115195_bib19","article-title":"First-line combination therapy versus first-line monotherapy for primary hypertension","volume":"2020","author":"Garj\u00f3n","year":"2020","journal-title":"Cochrane Database Syst. Rev."},{"issue":"23","key":"10.1016\/j.fct.2024.115195_bib20","doi-asserted-by":"crossref","DOI":"10.3390\/ijms222312827","article-title":"The mtt assay: utility, limitations, pitfalls, and interpretation in bulk and single-cell analysis","volume":"22","author":"Ghasemi","year":"2021","journal-title":"Int. J. Mol. Sci."},{"issue":"3","key":"10.1016\/j.fct.2024.115195_bib21","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1124\/jpet.119.257113","article-title":"Pharmacokinetic and pharmacodynamic properties of drug delivery systems","volume":"370","author":"Glassman","year":"2019","journal-title":"J. Pharmacol. Exp. Therapeut."},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib22","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-05984-9","article-title":"Chronic high-sodium diet intake after weaning lead to neurogenic hypertension in adult Wistar rats","volume":"7","author":"Gomes","year":"2017","journal-title":"Sci. Rep."},{"issue":"Issue 4","key":"10.1016\/j.fct.2024.115195_bib23","article-title":"Markers of renal function tests","volume":"2","author":"Gowda","year":"2010","journal-title":"www.najms.org North American Journal of Medical Sciences"},{"key":"10.1016\/j.fct.2024.115195_bib52","doi-asserted-by":"crossref","DOI":"10.1177\/17562848231163410","article-title":"Drug-induced liver injury: a comprehensive review","volume":"16","author":"Hosack","year":"2023","journal-title":"Therap. Adv. Gastroenterol."},{"key":"10.1016\/j.fct.2024.115195_bib24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.smrv.2018.02.003","article-title":"Insomnia and hypertension: a systematic review","volume":"41","author":"Jarrin","year":"2018","journal-title":"Sleep Med. Rev."},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib25","doi-asserted-by":"crossref","DOI":"10.1186\/s12889-018-5276-1","article-title":"The prevalence of alcohol dependence and its association with hypertension: a population-based cross-sectional study4 in Xuzhou city, China","volume":"18","author":"Ji","year":"2018","journal-title":"BMC Publ. Health"},{"key":"10.1016\/j.fct.2024.115195_bib26","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.phrs.2017.11.003","article-title":"Hypertension and cardiovascular risk: general aspects","volume":"129","author":"Kjeldsen","year":"2018","journal-title":"Pharmacol. Res."},{"issue":"10","key":"10.1016\/j.fct.2024.115195_bib27","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"10.1016\/j.fct.2024.115195_bib29","author":"Luft"},{"issue":"4","key":"10.1016\/j.fct.2024.115195_bib30","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1177\/0261192920965977","article-title":"A review of in silico tools as alternatives to animal testing: principles, resources and applications","volume":"48","author":"Madden","year":"2020","journal-title":"ATLA, Altern. Lab. Anim."},{"key":"10.1016\/j.fct.2024.115195_bib31","first-page":"817","article-title":"The past and present of serum aminotransferases and the future of liver injury biomarkers","volume":"15","author":"McGill","year":"2016","journal-title":"EXCLI Journal"},{"key":"10.1016\/j.fct.2024.115195_bib32","article-title":"Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"Journal oflmmunologicalMethods"},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib33","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1016\/j.jep.2010.01.022","article-title":"Acute and sub-chronic oral toxicity profiles of the aqueous extract of Polygala fruticosa in female mice and rats","volume":"128","author":"Mukinda","year":"2010","journal-title":"J. Ethnopharmacol."},{"issue":"5","key":"10.1016\/j.fct.2024.115195_bib34","doi-asserted-by":"crossref","first-page":"641","DOI":"10.4093\/dmj.2021.0220","article-title":"Assessment of insulin secretion and insulin resistance in human","volume":"45","author":"Park","year":"2021","journal-title":"Diabetes and Metabolism Journal"},{"issue":"8","key":"10.1016\/j.fct.2024.115195_bib35","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.2215\/CJN.11290821","article-title":"Drug-induced acute kidney injury","volume":"17","author":"Perazella","year":"2022","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"10.1016\/j.fct.2024.115195_bib36","article-title":"Revised methods for the Salmonella mutagenicity test","volume":"113","author":"Press","year":"1983","journal-title":"Mutat. Res."},{"key":"10.1016\/j.fct.2024.115195_bib37","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/wcms.1240","article-title":"In silico toxicology: computational methods for the prediction of chemical toxicity","author":"Raies","year":"2016","journal-title":"Wiley Interdiscip. Rev. Comput. Mol. Sci."},{"key":"10.1016\/j.fct.2024.115195_bib38","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/B978-0-323-98367-9.00012-3","article-title":"In silico methods for the prediction of drug toxicity","volume":"II","author":"Rajpoot","year":"2022","journal-title":"Pharmacokinetics and Toxicokinetic Considerations"},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib39","doi-asserted-by":"crossref","DOI":"10.1186\/s12929-016-0303-y","article-title":"Mechanisms of inflammatory responses and development of insulin resistance: how are they interlinked?","volume":"23","author":"Rehman","year":"2016","journal-title":"J. Biomed. Sci."},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib40","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1124\/pr.117.014373","article-title":"G protein\u2013coupled receptors targeting insulin resistance, obesity, and type 2 diabetes mellitus","volume":"70","author":"Riddy","year":"2018","journal-title":"Pharmacol. Rev."},{"issue":"5","key":"10.1016\/j.fct.2024.115195_bib41","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1016\/j.coph.2013.06.001","article-title":"In silico methods to predict drug toxicity","volume":"13","author":"Roncaglioni","year":"2013","journal-title":"Curr. Opin. Pharmacol."},{"key":"10.1016\/j.fct.2024.115195_bib42","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejmech.2022.114642","article-title":"Discovery of small-molecule modulators of the secretin receptor: purmorphamine as novel anti-hypertensive agent","volume":"242","author":"Singh","year":"2022","journal-title":"Eur. J. Med. Chem."},{"issue":"3","key":"10.1016\/j.fct.2024.115195_bib43","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1038\/nchembio.142","article-title":"A small molecule that binds Hedgehog and blocks its signaling in human cells","volume":"5","author":"Stanton","year":"2009","journal-title":"Nat. Chem. Biol."},{"issue":"5","key":"10.1016\/j.fct.2024.115195_bib44","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1111\/jch.13531","article-title":"First-line treatment of essential hypertension: a real-world analysis across four antihypertensive treatment classes","volume":"21","author":"Stapff","year":"2019","journal-title":"J. Clin. Hypertens."},{"key":"10.1016\/j.fct.2024.115195_bib45","series-title":"Repeated Dose 90-Day Oral Toxicity Study in Rodents","year":"2018"},{"key":"10.1016\/j.fct.2024.115195_bib46","series-title":"Chronic Toxicity Studies","year":"2018"},{"key":"10.1016\/j.fct.2024.115195_bib28","series-title":"In: Interpretation of Equine Laboratory Diagnostics","article-title":"Urine analysis","author":"Sharkey","year":"2017"},{"key":"10.1016\/j.fct.2024.115195_bib47","doi-asserted-by":"crossref","unstructured":"Walum, E. (n.d.). Acute Oral Toxicity. http:\/\/ehpnetl.niehs.nih.gov\/docs\/1998\/Suppl-2\/497-503walum\/abstract.html.","DOI":"10.1289\/ehp.98106497"},{"key":"10.1016\/j.fct.2024.115195_bib48","article-title":"Topic 3.13 Use of NOAEL, benchmark dose, and other models for human risk assessment of hormonally active substances","volume":"75","author":"Woodrow Setzer","year":"2003","journal-title":"Pure Appl. Chem."},{"issue":"4","key":"10.1016\/j.fct.2024.115195_bib49","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1155\/S1064744901000412","article-title":"Urinalysis and urinary tract infection: update for clinicians","volume":"9","author":"Young","year":"2001","journal-title":"Infect. Dis. Obstet. Gynecol."},{"issue":"1","key":"10.1016\/j.fct.2024.115195_bib50","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-019-50634-x","article-title":"Loss of secretin results in systemic and pulmonary hypertension with cardiopulmonary pathologies in mice","volume":"9","author":"Zaw","year":"2019","journal-title":"Sci. Rep."},{"key":"10.1016\/j.fct.2024.115195_bib51","series-title":"Mutation Research - Genetic Toxicology and Environmental Mutagenesis","first-page":"43","article-title":"The test that changed the world: the Ames test and the regulation of chemicals","author":"Zeiger","year":"2019"}],"container-title":["Food and Chemical Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691524007610?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0278691524007610?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T19:27:25Z","timestamp":1762284445000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0278691524007610"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2]]},"references-count":52,"alternative-id":["S0278691524007610"],"URL":"https:\/\/doi.org\/10.1016\/j.fct.2024.115195","relation":{},"ISSN":["0278-6915"],"issn-type":[{"value":"0278-6915","type":"print"}],"subject":[],"published":{"date-parts":[[2025,2]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Preclinical toxicity evaluation of the novel anti-hypertensive compound KSD179019","name":"articletitle","label":"Article Title"},{"value":"Food and Chemical Toxicology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.fct.2024.115195","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115195"}}