{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T23:58:28Z","timestamp":1790294308395,"version":"4.1.0"},"reference-count":84,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,19]],"date-time":"2025-10-19T00:00:00Z","timestamp":1760832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Mercury exposure has been linked to male infertility. Given that mercury chloride (HgCl2) may promote an oxido-inflammatory milieu associated with pathophysiological derangements, it is hypothesised that Thymoquinone (TQ), an antioxidant and anti-inflammatory agent, may mitigate the gradual harmful effects of mercury exposure on rat testes, epididymis, and hypothalamus, as these organs are vital to reproductive function. To test this hypothesis, 40 rats (strain: Wistar; sex: male) were randomly assigned to five cohorts of eight rats each. After a 7-day acclimation, treatments were dispensed for 28 consecutive days accordingly: Cohort I: distilled water only, as control; Cohort II: HgCl2 only (20 \u00b5g\/mL); Cohort III: TQ only (2.5 mg\/kg); Cohort IV: HgCl2 + TQ (20 \u00b5g\/mL + 2.5 mg\/kg); and Cohort V: HgCl2 + TQ (20 \u00b5g\/mL + 5 mg\/kg). Co-treatment with TQ preserved the body and organ weight of the HgCl2 exposed animals. However, TQ did not reduce HgCl2-induced dysfunction in sperm function and morphology. The serum follicle-stimulating hormone (FSH), luteinising hormone (LH), and testosterone were increased significantly (p &lt; 0.05) by TQ co-treatment, while decreasing the prolactin level. TQ administration also increased (p &lt; 0.05) testicular enzymes, including alkaline phosphatase (ALP), lactate dehydrogenase (LDH), acid phosphatase (ACP), and glucose-6-phosphate dehydrogenase (G6PD) activities, which HgCl2 decreased. TQ administration increased (p &lt; 0.05) HgCl2-induced decreases in catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), glutathione-s-transferase (GST), and total sulfhydryl group (TSH) levels in the testes, epididymis, and hypothalamus of experimental rats. Further, TQ reduced HgCl2-mediated increases in RONS-reactive oxygen and nitrogen species; LPO\u2013lipid peroxidation; PC\u2013protein carbonyl formation; and XO\u2013xanthine oxidase activity. Furthermore, levels of inflammatory biomarkers, including tumour necrosis factor alpha (TNF-\u03b1), nitric oxide (NO), interleukin-1 beta (IL-1\u03b2), and myeloperoxidase (MPO), were decreased (p &lt; 0.05) in the co-treated groups, with a higher dose of TQ (5.0 mg\/kg) showing a more pronounced protective effect. Additionally, TQ co-administration increased Bax and decreased Bcl-2 and p53 protein levels (p &lt; 0.05), thereby protecting the rats\u2019 testes, epididymis, and hypothalamus from HgCl2-induced apoptosis. Molecular docking simulation analysis revealed TQ interaction dynamics with PPAR-\u03b1 and PPAR-\u03b4 to suppress NF-kB-mediated pro-inflammatory sequela as well as activate Nrf-2-mediated antioxidant defence system. These predicted biological effects of TQ resonate with the findings from the in vivo studies. Therefore, supplementation with TQ may help reduce chemical-induced toxicities, including HgCl2\u2018s reproductive toxicity.<\/jats:p>","DOI":"10.3390\/toxics13100896","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T13:54:41Z","timestamp":1760968481000},"page":"896","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Thymoquinone Protective Effect Against Mercury-Induced Reproductive Derangement in Rats: In Vivo and In Silico Investigation"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4973-0376","authenticated-orcid":false,"given":"Solomon","family":"Owumi","sequence":"first","affiliation":[{"name":"Department of Biochemistry, University of Ibadan, Ibadan 200005, Oyo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moses","family":"Otunla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pelumi","family":"Akindipe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Ibadan, Ibadan 200005, Oyo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5315-2695","authenticated-orcid":false,"given":"Uche","family":"Arunsi","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesutosin O.","family":"Babalola","sequence":"additional","affiliation":[{"name":"Nutrition and Industrial Biochemistry Research Laboratories, Department of Biochemistry, University of Ibadan, Ibadan 200005, Oyo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7435-7251","authenticated-orcid":false,"given":"Chioma E.","family":"Irozuru","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Montana State University, Bozeman, MT 59719, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad","family":"Altayyar","sequence":"additional","affiliation":[{"name":"Naz Coker Ovarian Cancer Research Centre (NOVARC), Nottingham Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham NG7 2RD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bayode","family":"Oluwawibe","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, University of Ibadan, Ibadan 200005, Oyo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olatunde","family":"Owoeye","sequence":"additional","affiliation":[{"name":"Neuroanatomy Research Laboratories, Department of Anatomy, University of Ibadan, Ibadan 200005, Oyo State, Nigeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2248-9551","authenticated-orcid":false,"given":"Adegboyega K.","family":"Oyelere","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1803","DOI":"10.1071\/RD16310","article-title":"Reproductive dysfunction after mercury exposure at low levels: Evidence for a role of glutathione peroxidase (GPx) 1 and GPx4 in male rats","volume":"29","author":"Martinez","year":"2017","journal-title":"Reprod. 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