{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T14:51:09Z","timestamp":1787496669293,"version":"build-2736575974"},"reference-count":36,"publisher":"FapUNIFESP (SciELO)","license":[{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,1,1]],"date-time":"2025-01-01T00:00:00Z","timestamp":1735689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Imam Abdulrahman bin Faisal University in Dammam","award":["2017-102-Sci"],"award-info":[{"award-number":["2017-102-Sci"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Braz. J. Biol."],"abstract":"<jats:p>Abstract The increasing use of medicinal plants in traditional and modern therapies necessitates thorough toxicological evaluations to ensure their safety. Chrozophora genus includes 7-8 species that belong to the Euphorbiaceae family, distributed in Pakistan, India, West Africa, and the Mediterranean with four species found in the Kingdom of Saudi Arabia (KSA). This study evaluates the subacute toxicity of the ethyl acetate extract (EtOAcE) of Chrozophora tinctoria in male and female rats. Over 14 days, rats were daily administered the extract at doses of 50, 100, and 200 mg. Mortality was observed at a rate of one rat per group. Female rats showed a significant reduction in body weight, while organ weights remained unaffected. Kidney function tests revealed significant increases in bilirubin and creatinine levels in male rats at 200 mg, and uric acid levels in female rats at the same dosage. Liver enzyme analysis indicated significant elevations in ALP, ALT, and GGT levels in both sexes at various dosages. Glucose levels increased significantly in female rats at 200 mg\/kg, with no significant changes in cortisol levels in either sex. Histopathological examinations demonstrated notable abnormalities in liver, kidney, spleen, and small intestine tissues. These data demonstrate the essentiality of careful evaluation and monitoring when considering C. tinctoria for medicinal use, highlighting the need for further studies on its long-term safety and therapeutic index.<\/jats:p>","DOI":"10.1590\/1519-6984.290065","type":"journal-article","created":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:54:07Z","timestamp":1739512447000},"source":"Crossref","is-referenced-by-count":1,"title":["Subacute toxicity of Chrozophora Tinctoria extract: biochemical and histopathological changes in rats"],"prefix":"10.1590","volume":"85","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6203-2070","authenticated-orcid":false,"given":"N. F.","family":"AlAhmady","sequence":"first","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9854-5230","authenticated-orcid":false,"given":"M. G.","family":"Al-Mutary","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9287-9934","authenticated-orcid":false,"given":"H. A.","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2145-5138","authenticated-orcid":false,"given":"N. K.","family":"Alaqeel","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2213-7174","authenticated-orcid":false,"given":"F. M.","family":"Alkhulaifi","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9051-9639","authenticated-orcid":false,"given":"A. A.","family":"Al-Eidan","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-5822","authenticated-orcid":false,"given":"A. F.","family":"Almousa","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia; Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9933-9837","authenticated-orcid":false,"given":"R. A.","family":"Aldahhan","sequence":"additional","affiliation":[{"name":"Imam Abdulrahman Bin Faisal University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1887-7789","authenticated-orcid":false,"given":"N.","family":"Abutaha","sequence":"additional","affiliation":[{"name":"King Saud University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1900-8446","authenticated-orcid":false,"given":"A.","family":"Ammari","sequence":"additional","affiliation":[{"name":"King Saud University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8608-334X","authenticated-orcid":false,"given":"A. R.","family":"Alhimaidi","sequence":"additional","affiliation":[{"name":"King Saud University,  Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"530","published-online":{"date-parts":[[2025]]},"reference":[{"issue":"1","key":"ref1","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/s13002-018-0263-2","article-title":"Traditional use of ethnomedicinal native plants in the Kingdom of Saudi Arabia","volume":"15","author":"AATI H.","year":"2019","journal-title":"Journal of Ethnobiology and Ethnomedicine"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.phytol.2015.05.008","article-title":"Anti-inflammatory activity of flavonoids from Chrozophora tinctoria","volume":"13","author":"ABDALLAH H.M.","year":"2015","journal-title":"Phytochemistry Letters"},{"issue":"1","key":"ref3","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1186\/s12906-017-1852-7","article-title":"In vitro induction of human embryonal carcinoma differentiation by a crude extract of Rhazya stricta","volume":"17","author":"ALAGRAFI F.S.","year":"2017","journal-title":"BMC Complementary and Alternative Medicine"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.toxrep.2020.10.001","article-title":"Evaluation of acute and sub-acute toxicity of selected traditional antiurolithiatic medicinal plant extracts in Wistar albino rats","volume":"7","author":"ALELIGN T.","year":"2020","journal-title":"Toxicology Reports"},{"issue":"6","key":"ref5","doi-asserted-by":"crossref","first-page":"786","DOI":"10.3390\/ph16060786","article-title":"Evaluation of sex differences in preclinical pharmacology research: how far is left to go?","volume":"16","author":"ALLEGRA S.","year":"2023","journal-title":"Pharmaceuticals (Basel, Switzerland)"},{"issue":"1","key":"ref6","doi-asserted-by":"crossref","first-page":"5214","DOI":"10.1038\/s41598-020-62149-x","article-title":"Solvent extraction and gas chromatography-mass spectrometric determination of probable carcinogen 1,4-dioxane in cosmetic products","volume":"10","author":"ALSOHAIMI I.H.","year":"2020","journal-title":"Scientific Reports"},{"issue":"4","key":"ref7","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1590\/S0074-02762002000400017","article-title":"Cytotoxic and antiviral activities of Colombian medicinal plant extracts of the Euphorbia genus","volume":"97","author":"BETANCUR-GALVIS L.A.","year":"2002","journal-title":"Memorias do Instituto Oswaldo Cruz"},{"issue":"5","key":"ref8","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1111\/j.1478-3231.2008.01716.x","article-title":"Bilirubin in clinical practice: A review","volume":"28","author":"FEVERY J.","year":"2008","journal-title":"Liver International"},{"issue":"1","key":"ref9","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1177\/0192623316677327","article-title":"Sex differences in human and animal toxicology","volume":"45","author":"GOCHFELD M.","year":"2017","journal-title":"Toxicologic Pathology"},{"issue":"11","key":"ref10","doi-asserted-by":"crossref","DOI":"10.1111\/jfbc.13036","article-title":"Determination of phenolic compounds, antioxidant and anticancer activity of Chrozophora tinctoria accessions collected from different regions of Iran","volume":"43","author":"GOLKAR P.","year":"2019","journal-title":"Journal of Food Biochemistry"},{"issue":"2","key":"ref11","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.aohep.2019.08.004","article-title":"The relative expression of hepatocellular and cholestatic liver enzymes in adult patients with liver disease","volume":"19","author":"ILUZ-FREUNDLICH D.","year":"2020","journal-title":"Annals of Hepatology"},{"issue":"13","key":"ref12","doi-asserted-by":"crossref","first-page":"4321","DOI":"10.3390\/molecules27134321","article-title":"Extraction and fractionation of prokinetic phytochemicals from Chrozophora tinctoria and their bioactivities","volume":"27","author":"IQBAL A.","year":"2022","journal-title":"Molecules (Basel, Switzerland)"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"158","DOI":"10.1016\/j.toxrep.2024.01.010","article-title":"Toxicological evaluation of chronic oral administration of Justicia schimperiana (Hochst. ex Nees) T. Anderson leaf 80% methanolic extract in Wistar albino rats","volume":"12","author":"JEGNIE M.","year":"2024","journal-title":"Toxicology Reports"},{"issue":"1","key":"ref14","first-page":"27","article-title":"Herbal versus synthetic drugs: beliefs and facts","volume":"4","author":"KARIMI A.","year":"2015","journal-title":"Journal of Nephropharmacology"},{"issue":"1","key":"ref15","article-title":"The reproductive toxicity associated with Dodonaea viscosa, a folk medicinal plant in Saudi Arabia","volume":"2021","author":"KHAN M.F.","year":"2021","journal-title":"Evidence-Based Complementary and Alternative Medicine"},{"key":"ref16","article-title":"Natural products and dietary interventions on liver enzymes: an umbrella review and evidence map","volume":"11","author":"LI Z.","year":"2024","journal-title":"Frontiers in Nutrition"},{"issue":"1","key":"ref17","article-title":"Pharmacological evaluation of Chrozophora tinctoria as wound healing potential in diabetic rat\u2019s model","volume":"2016","author":"MAURYA H.","year":"2016","journal-title":"BioMed Research International"},{"issue":"1","key":"ref18","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/s12906-021-03470-4","article-title":"Acute and sub-acute oral toxicity of aqueous whole leaf and green rind extracts of Aloe vera in Wistar rats","volume":"22","author":"NALIMU F.","year":"2022","journal-title":"BMC Complementary Medicine and Therapies."},{"issue":"1","key":"ref19","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1080\/13880209.2016.1277767","article-title":"Phytochemical analysis, antiproliferative and antioxidant activities of Chrozophora tinctoria: a natural dye plant","volume":"55","author":"OKE-ALTUNTAS F.","year":"2017","journal-title":"Pharmaceutical Biology"},{"key":"ref20","series-title":"Test No. 407: Repeated Dose 28-day Oral Toxicity Study in Rodents","year":"2008"},{"key":"ref21","doi-asserted-by":"crossref","DOI":"10.1016\/j.cotox.2022.100371","article-title":"Plant vs. kidney: evaluating nephrotoxicity of botanicals with the latest toxicological tools","volume":"32","author":"PEARSON A.","year":"2022","journal-title":"Current Opinion in Toxicology"},{"issue":"1","key":"ref22","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1186\/s13643-021-01882-4","article-title":"Acceptance and use of complementary and alternative medicine among medical specialists: A 15-year systematic review and data synthesis","volume":"11","author":"PHUTRAKOOL P.","year":"2022","journal-title":"Systematic Reviews"},{"issue":"14","key":"ref23","doi-asserted-by":"crossref","first-page":"5011","DOI":"10.3390\/ijms21145011","article-title":"Potential hepatotoxins found in herbal medicinal products: a systematic review","volume":"21","author":"QUAN N.V.","year":"2020","journal-title":"International Journal of Molecular Sciences"},{"issue":"2","key":"ref24","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.fitote.2003.12.012","article-title":"Medicinal plant diversity in the flora of Saudi Arabia: A report on seven plant families","volume":"75","author":"RAHMAN M.A.","year":"2004","journal-title":"Fitoterapia"},{"issue":"2","key":"ref25","doi-asserted-by":"crossref","first-page":"472S","DOI":"10.1093\/ajcn\/87.2.472S","article-title":"Evaluation of botanicals for improving human health","volume":"87","author":"RIBNICKY D.M.","year":"2008","journal-title":"The American Journal of Clinical Nutrition"},{"issue":"121","key":"ref26","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1186\/s12944-015-0123-1","article-title":"The role of fatty acids in insulin resistance","volume":"14","author":"SEARS B.","year":"2015","journal-title":"Lipids in Health and Disease"},{"issue":"7","key":"ref27","doi-asserted-by":"crossref","first-page":"2143","DOI":"10.3390\/molecules27072143","article-title":"Prokinetic and laxative effects of Chrozophora tinctoria whole plant extract","volume":"27","author":"SHER A.A.","year":"2022","journal-title":"Molecules (Basel, Switzerland)"},{"issue":"9","key":"ref28","doi-asserted-by":"crossref","first-page":"776","DOI":"10.3390\/toxics11090776","article-title":"Sex-specific effects of short-term oral administration of food-grade titanium dioxide nanoparticles in the liver and kidneys of adult rats","volume":"11","author":"TASSINARI R.","year":"2023","journal-title":"Toxics"},{"issue":"2","key":"ref29","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.fitote.2007.07.016","article-title":"Medicinal plants popularly used in the villages of Yunt Mountain (Manisa-Turkey)","volume":"79","author":"UGURLU E.","year":"2008","journal-title":"Fitoterapia"},{"issue":"10","key":"ref30","doi-asserted-by":"crossref","first-page":"2706","DOI":"10.1016\/j.sjbs.2020.06.020","article-title":"A review on ethno-medicinal plants used in traditional medicine in the Kingdom of Saudi Arabia","volume":"27","author":"ULLAH R.","year":"2020","journal-title":"Saudi Journal of Biological Sciences"},{"issue":"4","key":"ref31","doi-asserted-by":"crossref","first-page":"488","DOI":"10.4314\/ajtcam.v4i4.31242","article-title":"Phytochemical and antimicrobial effects of Chrozophora senegalensis","volume":"4","author":"USMAN H.","year":"2007","journal-title":"African Journal of Traditional, Complementary, and Alternative Medicines"},{"issue":"2","key":"ref32","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1124\/mol.109.056705","article-title":"Sex differences in the expression of hepatic drug metabolizing enzymes","volume":"76","author":"WAXMAN D.J.","year":"2009","journal-title":"Molecular Pharmacology"},{"issue":"15","key":"ref33","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.2165\/00002018-200326150-00002","article-title":"Drug interactions between herbal and prescription medicines","volume":"26","author":"WILLIAMSON E.M.","year":"2003","journal-title":"Drug Safety"},{"key":"ref34","article-title":"Nephrotoxicity of herbal medicine and its prevention","volume":"11","author":"XU X.","year":"2020","journal-title":"Frontiers in Pharmacology"},{"issue":"10","key":"ref35","doi-asserted-by":"crossref","first-page":"1605","DOI":"10.2215\/CJN.11571017","article-title":"Nephrotoxicity and Chinese herbal medicine","volume":"13","author":"YANG B.","year":"2018","journal-title":"Clinical Journal of the American Society of Nephrology; CJASN"},{"issue":"1","key":"ref36","doi-asserted-by":"crossref","first-page":"33","DOI":"10.3390\/metabo13010033","article-title":"Sex differences in the in vivo exposure process of multiple components of Gelsemium elegans in rats","volume":"13","author":"ZUO M.T.","year":"2022","journal-title":"Metabolites"}],"container-title":["Brazilian Journal of Biology"],"original-title":["Toxicidade subaguda do extrato de Chrozophora Tinctoria: altera\u00e7\u00f5es bioqu\u00edmicas e histopatol\u00f3gicas em ratos"],"link":[{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_pdf&pid=S1519-69842025000100112&tlng=en","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,2,14]],"date-time":"2025-02-14T05:54:21Z","timestamp":1739512461000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.scielo.br\/scielo.php?script=sci_arttext&pid=S1519-69842025000100112&tlng=en"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025]]},"references-count":36,"alternative-id":["S1519-69842025000100112"],"URL":"https:\/\/doi.org\/10.1590\/1519-6984.290065","relation":{},"ISSN":["1678-4375","1519-6984"],"issn-type":[{"value":"1678-4375","type":"electronic"},{"value":"1519-6984","type":"print"}],"subject":[],"published":{"date-parts":[[2025]]},"article-number":"e290065"}}