{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T18:39:14Z","timestamp":1785523154004,"version":"3.56.0"},"reference-count":49,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,4,17]],"date-time":"2015-04-17T00:00:00Z","timestamp":1429228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Fundamemntal Clinical Pharma"],"published-print":{"date-parts":[[2015,6]]},"abstract":"Abstract<\/jats:title>Cyclophosphamide (CYP<\/jats:styled-content>) is a chemotherapeutic agent with a potent ovarian toxic effect. CYP<\/jats:styled-content> induces granulosa cell apoptosis and oxidative stress. Irbesartan (IRB<\/jats:styled-content>) is a unique ARB<\/jats:styled-content> with a peroxisome proliferator\u2010activated receptor\u2010gamma (PPAR<\/jats:styled-content>\u2010\u03b3) agonistic activity. As PPAR<\/jats:styled-content>\u2010\u0263 activation exerts anti\u2010inflammatory effects and reduces ROS<\/jats:styled-content> production, IRB<\/jats:styled-content> may further reduce inflammatory chemokine expression and suppress apoptotic cell death. Therefore, this study aimed to evaluate the effects of IRB<\/jats:styled-content> on the development of CYP<\/jats:styled-content>\u2010induced ovarian damage. Rats were divided into four groups: control group, IRB<\/jats:styled-content> group (100\u00a0mg\/kg, orally), CYP<\/jats:styled-content> group (100\u00a0mg\/kg, i.p<\/jats:italic>. single injection), and IRB<\/jats:styled-content>+CYP<\/jats:styled-content> group (IRB<\/jats:styled-content> administered 9\u00a0days before and 6\u00a0days after CYP<\/jats:styled-content> administration). Rats sacrificed on day\u00a016 of experiment; estradiol (E<\/jats:styled-content>2), FSH<\/jats:styled-content>, and TNF<\/jats:styled-content>\u2010\u03b1 levels were estimated in serum. Reduced glutathione (GSH<\/jats:styled-content>), malondialdehyde (MDA<\/jats:styled-content>), superoxide dismutase (SOD<\/jats:styled-content>) and caspase\u20103 activities, myeloperoxidase (MPO<\/jats:styled-content>), and IL<\/jats:styled-content>\u201010 levels were determined in ovarian tissues. Protein expressions of p53, caspase\u20103, K<\/jats:styled-content>i\u201067, and R<\/jats:styled-content>ad\u201051 were estimated by immunohistochemical and Western blot techniques. CYP<\/jats:styled-content> produced ovarian damage as indicated from the decline in serum E<\/jats:styled-content>2; elevation in FSH<\/jats:styled-content>; unbalance in tissue oxidative stress parameters; increase in MPO<\/jats:styled-content>, TNF<\/jats:styled-content>\u2010\u03b1 levels, caspase\u20103 activity\/expression, p53, and R<\/jats:styled-content>ad\u201051 expression; and decrease in IL<\/jats:styled-content>\u201010 contents, without effect on K<\/jats:styled-content>i\u201067. On the other hand, IRB<\/jats:styled-content>, significantly reduced the toxic effects of CYP<\/jats:styled-content> as indicted from normalization of E<\/jats:styled-content>2, FSH<\/jats:styled-content>, oxidative stress, apoptotic, and inflammatory mediators. These data were further supported by histopathological studies. Thus, co\u2010administration of IRB<\/jats:styled-content> may be promising in alleviating the ovarian toxic effects of CYP<\/jats:styled-content>.<\/jats:p>","DOI":"10.1111\/fcp.12119","type":"journal-article","created":{"date-parts":[[2015,3,31]],"date-time":"2015-03-31T04:33:09Z","timestamp":1427776389000},"page":"286-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Irbesartan, an angiotensin II<\/scp> receptor antagonist, with selective PPAR<\/scp>\u2010gamma\u2010modulating activity improves function and structure of chemotherapy\u2010damaged ovaries in rats"],"prefix":"10.1111","volume":"29","author":[{"given":"Ihab T.","family":"Abdel\u2010Raheem","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Damanhour University Damanhour 22111 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal A.","family":"Omran","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Faculty of Pharmacy Damanhour University Damanhour 22111 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed Alaa","family":"Katary","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Toxicology Faculty of Pharmacy Damanhour University Damanhour 22111 Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,4,17]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nut.2012.11.004"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh120"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod52.2.365"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/acr.20605"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.111.095224"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/toxsci\/kfm087"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2004.02.067"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/14.7.1903"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1042\/bst0280056"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1383050"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/626319"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12031"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/1479-5876-11-229"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/HJH.0b013e32834f043b"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/fcp.12057"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phymed.2013.02.001"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20000025"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2011.04.008"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/000456328802500502"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-1759(81)90219-2"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1254\/jphs.FP0070122"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-9861(59)90090-6"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(78)90342-1"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/0027-5107(85)90216-7"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-8206.2012.01047.x"},{"key":"e_1_2_7_27_1","volume-title":"Theory and practice of histological techniques","author":"Banchrof J.D.","year":"1996"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/0041-008X(91)90310-B"},{"key":"e_1_2_7_29_1","first-page":"1476","article-title":"Cyclophosphamide\u2010induced ovarian damage and stem cell factor expression in rat ovaries","volume":"27","author":"Luo L.","year":"2007","journal-title":"Nan Fang Yi Ke Da Xue Xue Bao"},{"key":"e_1_2_7_30_1","first-page":"E4","article-title":"Hirsutism, virilism, polycystic ovarian disease, and the steroid\u2010gonadotropin\u2010feedback system: a career retrospective","volume":"302","author":"Mahesh V.B.","year":"2011","journal-title":"Endocrinol. 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