{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T03:34:13Z","timestamp":1789097653809,"version":"build-2803163510"},"reference-count":63,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T00:00:00Z","timestamp":1780444800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JoX"],"abstract":"<jats:p>Cadmium is a widespread environmental xenobiotic that poses serious risks to hepatic, renal, and male reproductive functions. Natural compounds such as silymarin, a bioactive extract from Silybum marianum, have gained attention for their protective potential against xenobiotic-induced toxicity. This study investigated whether subchronic oral administration of silymarin (30 mg\/kg) mitigates cadmium-induced toxicity (5 mg\/kg) in adult rats over six weeks. Twenty-four rats were assigned to four groups: control, cadmium-exposed, silymarin-treated, and co-treated. Biochemical, hematological, oxidative stress, and reproductive parameters were assessed. Sperm quality was evaluated using CASA, and testicular tissues were examined histologically. Cadmium exposure significantly reduced body weight (\u221230.8%), elevated transaminases (AST, ALT; p &lt; 0.01), increased serum creatinine and total cholesterol, and induced multi-organ oxidative stress, as reflected by elevated malondialdehyde and markedly reduced SOD, CAT, and thiol group levels in testicular, hepatic, and renal tissues (p &lt; 0.01). Sperm concentration dropped from 75.2 to 21.8 \u00d7 106\/mL, with total motility falling to 35% and progressive motility to 18%, accompanied by severe seminiferous tubule degeneration (Score III in 5 rats). Co-administration of silymarin partially restored these parameters, sperm concentration recovered to 38.5 \u00d7 106\/mL, total motility improved to 50.2%, and antioxidant enzyme activities and liver\/kidney biomarkers showed significant but incomplete recovery (p &lt; 0.05). Molecular docking revealed favorable binding affinities of silybin toward GPx (\u22128.4 kcal\/mol), CAT (\u22128.3 kcal\/mol), and SOD (\u22126.4 kcal\/mol), offering a preliminary computational hypothesis suggesting possible interactions between silybin and antioxidant enzymes, pending experimental validation. Silymarin alone exerted no adverse effects. These findings establish silymarin as a partial but promising multi-organ cytoprotectant against cadmium toxicity, and highlight the need for future studies optimizing dosing strategies, exploring longer treatment durations, and investigating combination approaches with metal chelators or Nrf2-activating agents to achieve complete tissue recovery.<\/jats:p>","DOI":"10.3390\/jox16030103","type":"journal-article","created":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T13:46:48Z","timestamp":1780494408000},"page":"103","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Subchronic Cadmium-Induced Xenobiotic Toxicity in Male Wistar Rats: Antioxidant and Reproductive Protection by Standardized Silymarin with Molecular Docking Insights"],"prefix":"10.3390","volume":"16","author":[{"given":"Imen","family":"Hammami","sequence":"first","affiliation":[{"name":"Laboratory of Population Health, Environmental Aggressors and Alternative Therapies (LR24ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"},{"name":"Department of Basic Sciences, Histology Embryology and Cell Biology Section, Faculty of Medicine of Tunis, University of Tunis El Manar, 15 Street Djebel Lakhdar, La Rabta, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6207-4641","authenticated-orcid":false,"given":"Fatma","family":"Arrari","sequence":"additional","affiliation":[{"name":"Higher Institute of Biotechnology of Beja, LR: Functional Physiology and Valorization of Bio-Resources, University of Jendouba, Beja 9000, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahma","family":"Mahjoub","sequence":"additional","affiliation":[{"name":"UR17SP01-Clinical Biology Laboratory, National Institute of Nutrition and Food Technology, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ridha Ben","family":"Ali","sequence":"additional","affiliation":[{"name":"Laboratory of Population Health, Environmental Aggressors and Alternative Therapies (LR24ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haifa El","family":"Hentati","sequence":"additional","affiliation":[{"name":"National Gene Bank of Tunisia, Boulevard of the Leader Yasser Arafat, Ministry of Local Affairs and Environment, Tunis 1080, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8650-0935","authenticated-orcid":false,"given":"Afef","family":"Nahdi","sequence":"additional","affiliation":[{"name":"Laboratory of Population Health, Environmental Aggressors and Alternative Therapies (LR24ES10), Faculty of Medicine of Tunis, University of Tunis El Manar, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1884-4821","authenticated-orcid":false,"given":"Eduardo Alberto","family":"L\u00f3pez-Maldonado","sequence":"additional","affiliation":[{"name":"Faculty of Chemical Sciences and Engineering, Autonomous University of Baja California, Tijuana 22424, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9438-9154","authenticated-orcid":false,"given":"Emna","family":"Talbi","sequence":"additional","affiliation":[{"name":"UR17SP01-Clinical Biology Laboratory, National Institute of Nutrition and Food Technology, Tunis 1007, Tunisia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e04691","DOI":"10.1016\/j.heliyon.2020.e04691","article-title":"Heavy metal pollution in the environment and their toxicological effects on humans","volume":"6","author":"Briffa","year":"2020","journal-title":"Heliyon"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Balali-Mood, M., Naseri, K., Tahergorabi, Z., Khazdair, M., and Sadeghi, M. 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