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Piperine (PIP) is an alkaloid that has antioxidant, antiapoptotic, and anti\u2010inflammatory activities. This study was investigated the protective effects of PIP on CP\u2010induced testicular toxicity in the mice. In this experimental study, 48 adult male BALB\/c mice (30\u221235\u2009g) were divided into six groups (<jats:italic>n<\/jats:italic>\u2009=\u20098), receiving normal saline (C), 5\u2009mg\/kg of PIP (PIP5), 10\u2009mg\/kg of PIP (PIP10), 200\u2009mg\/kg of CP, 200\u2009mg\/kg of CP\u2009+\u2009PIP5, and 200\u2009mg\/kg of CP\u2009+\u2009PIP10. On the eighth day of the study, blood and testis samples were prepared for serum testosterone hormone quantification, sperm analysis, histological, and immunohistochemical assays. The results of this study showed that CP induced testicular toxicity with the decrease of sperm count, motility, and viability. Also, CP treatment caused histological structure alterations in the testis, including exfoliation, degeneration, vacuolation of spermatogenic cells, and reducing the thickness of the epithelium and the diameter of the seminiferous tubule. In addition, CP decreased glutathione (GSH) levels, increased malondialdehyde (MDA) levels, Caspase\u20103, and NF\u2010\u03baB. At the same time, PIP treatment reduced testicular histopathological abnormalities, oxidative stress, and apoptosis that were induced by CP. These results showed that PIP improved CP\u2010induced testicular toxicity in mice, which can be related to its antioxidant, antiapoptotic, and anti\u2010inflammatory activities.<\/jats:p>","DOI":"10.1002\/jbt.23696","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T05:33:45Z","timestamp":1711431225000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Piperine mitigates oxidative stress, inflammation, and apoptosis in the testicular damage induced by cyclophosphamide in mice"],"prefix":"10.1002","volume":"38","author":[{"given":"Fatemeh","family":"Fani","sequence":"first","affiliation":[{"name":"Department of Anatomy, Molecular and Cell Biology Research Center, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"},{"name":"Student Research Committee, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8055-8036","authenticated-orcid":false,"given":"Seyed Jalal","family":"Hosseinimehr","sequence":"additional","affiliation":[{"name":"Department of Radiopharmacy, Faculty of Pharmacy Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5994-786X","authenticated-orcid":false,"given":"Mehryar","family":"Zargari","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9851-3100","authenticated-orcid":false,"given":"Mansoureh","family":"Mirzaei","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Molecular and Cell Biology Research Center, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9649-2235","authenticated-orcid":false,"given":"Abbasali","family":"Karimpour Malekshah","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Molecular and Cell Biology Research Center, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4236-7439","authenticated-orcid":false,"given":"Fereshteh","family":"Talebpour Amiri","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Molecular and Cell Biology Research Center, Faculty of Medicine Mazandaran University of Medical Sciences Sari Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,3,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2021.120218"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocpiqo.2023.04.009"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32796"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2018.12.018"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43188-022-00149-x"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-023-27354-x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11255-022-03246-w"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1177\/0961203315622821"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-023-01134-1"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-023-29874-y"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jddst.2022.103306"},{"issue":"2","key":"e_1_2_10_13_1","volume":"54","author":"Timar M.","year":"2020","journal-title":"Andrologia"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.21608\/ejhm.2019.65258"},{"issue":"1","key":"e_1_2_10_15_1","first-page":"78","volume":"17","author":"Novin M. 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