{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,13]],"date-time":"2026-06-13T05:58:30Z","timestamp":1781330310713,"version":"3.54.1"},"reference-count":76,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T00:00:00Z","timestamp":1780012800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Andrology"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pro\u2010inflammatory cytokines, TNF and IL\u20101B, are essential for testicular homeostasis. Diacerein, an anti\u2010inflammatory drug, inhibits these cytokines,\u00a0impairing\u00a0M2 macrophages and Leydig cells (LCs).\u00a0However, its impact on Sertoli cells (SCs) and M1 (CD68) macrophages remains unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate\u00a0the impact of diacerein\u2010induced cytokine downregulation on SC integrity and the testicular immune profile.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      Male rats were treated with diacerein (100 mg\/kg) or saline for 30 days. The seminiferous epithelium was evaluated by light and transmission electron microscopy. The number of spermatocytes and Ki\u201067+ cells was quantified. SC structural (actin, vimentin, claudin\u20101, connexin\u201043) and functional (transferrin, Ldha) proteins, and the\u00a0interstitial immunolocalization of macrophage inhibitory factor (MIF), CD68, CD45, IL\u20101B, iNOS, NF\u2010\u03baB, and karyopherin were assessed, alongside immune response genes (\n                      <jats:italic>Tnfa, Il1b, Nfkb1, Nos2, Tgfb1<\/jats:italic>\n                      ) and nitrite levels.\u00a0TUNEL method was also performed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      TNF and IL\u20101B were downregulated; steroidogenesis and IL\u20101B production by LCs decreased,\u00a0coupled with\u00a0reduced MIF levels.\u00a0SCs exhibited electron\u2010dense cytoplasm, disrupted filaments, and decreased blood\u2013testis barrier proteins.\u00a0Transferrin and\n                      <jats:italic>Ldha<\/jats:italic>\n                      expression\u00a0were\u00a0reduced, underlying\u00a0reduced spermatocyte counts, arrested proliferation, and germ cell death.\u00a0TUNEL\u2010positive apoptotic bodies (probably from LCs) were found within macrophages. Despite increased CD45+ and CD68+ macrophages, a noninflammatory phenotype was observed due to NF\u2010\u03baB cytoplasmic sequestration and weak karyopherin expression, corroborating\n                      <jats:italic>Tgfb1<\/jats:italic>\n                      upregulation and reduced\n                      <jats:italic>Nos2<\/jats:italic>\n                      \u00a0expression and nitrite levels.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Basal cytokines are essential for SC structure and function. Despite testicular damage, diacerein shifted the immune response toward a homeostatic and immunotolerant profile, avoiding a self\u2010destructive inflammatory process.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/andr.70255","type":"journal-article","created":{"date-parts":[[2026,5,29]],"date-time":"2026-05-29T10:32:58Z","timestamp":1780050778000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Diacerein Disrupts Testicular Homeostasis: The Essential Role of Basal Cytokines in Maintaining Sertoli Cell Integrity and the Immune Microenvironment"],"prefix":"10.1111","author":[{"given":"Elide Loise Freitas de","family":"Jesus","sequence":"first","affiliation":[{"name":"Department of Morphology School of Dentistry Genetics, Orthodontics and Pediatric Dentistry, Laboratory of Histology and Embryology S\u00e3o Paulo State University (UNESP)  Araraquara S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9 Ac\u00e1cio Souza da","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Morphology and Genetics Federal University of S\u00e3o Paulo  S\u00e3o Paulo S\u00e3o Paulo Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olumide Stephen","family":"Akinsomisoye","sequence":"additional","affiliation":[{"name":"Faculty of Basic Medical Sciences Obafemi Awolowo University  Ile Ife Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erick J. 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