{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:09:30Z","timestamp":1787018970196,"version":"build-2736575974"},"reference-count":56,"publisher":"SAGE Publications","license":[{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Hum Exp Toxicol"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cyclophosphamide (Cyp) is associated with various organ toxicities. The study aimed to investigate the efficacy of zofenopril (Zf), thymoquinone (Thym), and their combination in Cyp-induced cardiotoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methodology<\/jats:title>\n                    <jats:p>Thirty rats were divided into five groups of six rats each. They received the following treatment orally for 19 days: Control (Con) and Cyp groups: normal saline. Zf: Zf 15\u00a0mg\/kg, Thym: Thym 80\u00a0mg\/kg, and Zf + Thym: a combination of both. A single dose of Cyp 200\u00a0mg\/kg intraperitoneally (IP) was given on day 17 of the experiment to all the groups except the Con. Cardiac, inflammatory, and apoptotic biomarkers, including troponin T, lactate dehydrogenase (LDH), CK-MB, hs-CRP, nuclear factor kappa B (NF-\u03baB), caspase-3, and total antioxidant capacity (TAC), along with lipid profile and histopathological lesions, were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Cyp resulted in cardiotoxicity as manifested by a significant increase in troponin T, CK-MB, caspase-3, hs-CRP, suppression of TAC level, and marked histopathological alterations in cardiac tissues. Zf, Thym, and their combination significantly reduced CK-MB levels. NF-\u03baB level was significantly decreased by Thym, while the combination of Zf and Thym significantly elevated TAC. hs-CRP was significantly reduced only by Zf. Caspase-3 were significantly lowered by both Zf and Thym individually, as well as by their combination.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Zf and Thym provided cardioprotection against Cyp-induced cardiotoxicity through distinct mechanisms. Zf exhibited anti-inflammatory effects, evidenced by a significant reduction in hs-CRP, along with anti-apoptotic activity. Thym significantly suppressed NF-\u03baB expression. Their combination enhanced antioxidant capacity, however, no superiority over individual treatments was observed concerning their other actions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/09603271251376594","type":"journal-article","created":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T15:07:14Z","timestamp":1756566434000},"update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":2,"title":["Cardioprotective effect of zofenopril, thymoquinone and their combination in cyclophosphamide-induced cardiotoxicity in rats"],"prefix":"10.1177","volume":"44","author":[{"given":"Sakar Karem","family":"Abdulla","sequence":"first","affiliation":[{"name":"Department of Basic Sciences, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ban Mousa","family":"Rashid","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2245-7322","authenticated-orcid":false,"given":"Karmand Salih","family":"Hamaamin","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neveen Nawzad","family":"Mahmood","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7658-9013","authenticated-orcid":false,"given":"Bushra Hassan","family":"Marouf","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemn Hassan","family":"Othman","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, College of Pharmacy, University of Sulaimani, Sulaymaniyah, Iraq"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,8,30]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/jphp.12641"},{"key":"e_1_3_6_3_2","article-title":"Effects of zofenopril on arterial stiffness in hypertension patients","author":"Pali\u0107 B","year":"2023","unstructured":"Pali\u0107 B, Brizi\u0107 I, Sher EK, et al. Effects of zofenopril on arterial stiffness in hypertension patients. Mol Biotechnol 2023, Published online 13 September.","journal-title":"Mol Biotechnol"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1161\/JAHA.116.003531"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvu026"},{"key":"e_1_3_6_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00088.2007"},{"issue":"7","key":"e_1_3_6_7_2","first-page":"e64913","article-title":"Roles of hydrogen sulfide (H2S) as a potential therapeutic agent in cardiovascular diseases: a narrative review","volume":"16","author":"Islam KN","year":"2024","unstructured":"Islam KN, Nguyen ID, Islam R, et al. Roles of hydrogen sulfide (H2S) as a potential therapeutic agent in cardiovascular diseases: a narrative review. Cureus 2024; 16(7): e64913.","journal-title":"Cureus"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.3390\/cells13020158"},{"key":"e_1_3_6_9_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2013.08.003"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1097\/FJC.0000000000000473"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1007\/s12325-018-0697-x"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.12.018"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.3390\/ph16060783"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.116019"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.4161\/oxim.3.5.13107"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/4965171"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1177\/2156587218757649"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.3390\/life13030786"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1155\/2022\/6276768"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.20369"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/1483041"},{"key":"e_1_3_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.vph.2021.106899"},{"issue":"5","key":"e_1_3_6_23_2","first-page":"199","article-title":"Ethical considerations in animal research: the principle of 3R\u2019s","volume":"73","author":"D\u00edaz L","year":"2020","unstructured":"D\u00edaz L, Zambrano E, Flores ME, et al. Ethical considerations in animal research: the principle of 3R\u2019s. Rev Investig Clin 2020; 73(5): 199\u2013209.","journal-title":"Rev Investig Clin"},{"issue":"4","key":"e_1_3_6_24_2","first-page":"313","article-title":"Protective effects of zofenopril on testicular torsion and detorsion injury in rats","volume":"8","author":"Altunoluk B","year":"2011","unstructured":"Altunoluk B, S\u00f6ylemez H, Bakan V, et al. Protective effects of zofenopril on testicular torsion and detorsion injury in rats. Urol J 2011; 8(4): 313\u2013319.","journal-title":"Urol J"},{"key":"e_1_3_6_25_2","doi-asserted-by":"publisher","DOI":"10.1080\/AC.67.1.2146570"},{"key":"e_1_3_6_26_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.1000412"},{"key":"e_1_3_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/ilar.43.4.244"},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00280-016-3233-1"},{"issue":"3","key":"e_1_3_6_29_2","first-page":"326","article-title":"An Angiotensin-converting enzyme inhibitor, zofenopril, prevents renal ischemia\/reperfusion injury in rats","volume":"36","author":"Altunoluk B","year":"2006","unstructured":"Altunoluk B, Soylemez H, Oguz F, et al. An Angiotensin-converting enzyme inhibitor, zofenopril, prevents renal ischemia\/reperfusion injury in rats. Ann Clin Lab Sci 2006; 36(3): 326\u2013332.","journal-title":"Ann Clin Lab Sci"},{"key":"e_1_3_6_30_2","volume-title":"Applying regression & correlation: a guide for students and researchers","author":"Miles J","year":"2001","unstructured":"Miles J, Shevlin M. Applying regression & correlation: a guide for students and researchers. Sage Publications, 2001."},{"key":"e_1_3_6_31_2","volume-title":"Statistical power analysis for the behavioral sciences","author":"Cohen J","year":"2009","unstructured":"Cohen J. Statistical power analysis for the behavioral sciences. 2nd ed. reprint. Psychology Press, 2009.","edition":"2"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.118822"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202100886"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-92430-6"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.3390\/life12081183"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1261270"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1155\/2018\/8503109"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-024-07574-0"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1080\/09553002.2021.1893856"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1177\/09603271221111440"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-018-2242-5"},{"key":"e_1_3_6_42_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S500375"},{"key":"e_1_3_6_43_2","doi-asserted-by":"publisher","DOI":"10.1186\/1476-9255-7-21"},{"key":"e_1_3_6_44_2","doi-asserted-by":"publisher","DOI":"10.1590\/1414-431x20187338"},{"key":"e_1_3_6_45_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)00782-8"},{"key":"e_1_3_6_46_2","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/8467406"},{"key":"e_1_3_6_47_2","doi-asserted-by":"publisher","DOI":"10.3390\/biomedicines11112897"},{"key":"e_1_3_6_48_2","doi-asserted-by":"publisher","DOI":"10.5772\/intechopen.73394"},{"key":"e_1_3_6_49_2","doi-asserted-by":"publisher","DOI":"10.3390\/ddc4010004"},{"key":"e_1_3_6_50_2","doi-asserted-by":"publisher","DOI":"10.2147\/JIR.S379725"},{"key":"e_1_3_6_51_2","doi-asserted-by":"crossref","unstructured":"Gelen V \u015eeng\u00fcl E Gedikli S et al. The effects of Quercetin on cyclophosphamide-induced cardiotoxicity in rats. Published online May 5 2021.","DOI":"10.21203\/rs.3.rs-443252\/v1"},{"key":"e_1_3_6_52_2","doi-asserted-by":"publisher","DOI":"10.1155\/2024\/7739710"},{"key":"e_1_3_6_53_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b22-00199"},{"key":"e_1_3_6_54_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2023.02.003"},{"key":"e_1_3_6_55_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejpain.2011.08.009"},{"key":"e_1_3_6_56_2","doi-asserted-by":"publisher","DOI":"10.3831\/KPI.2024.27.3.245"},{"key":"e_1_3_6_57_2","doi-asserted-by":"publisher","DOI":"10.1002\/ddr.22171"}],"container-title":["Human &amp; Experimental Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251376594","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/09603271251376594","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/09603271251376594","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:49:29Z","timestamp":1777448969000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/09603271251376594"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8]]},"references-count":56,"alternative-id":["10.1177\/09603271251376594"],"URL":"https:\/\/doi.org\/10.1177\/09603271251376594","relation":{},"ISSN":["0960-3271","1477-0903"],"issn-type":[{"value":"0960-3271","type":"print"},{"value":"1477-0903","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8]]},"article-number":"09603271251376594"}}