Asmaa S. Morsi , Hager M. Ramadan , Ahmed M. Youssef , Nadia A. Taha
{"title":"Mechanisms of PDC-induced testicular Toxicity: Oxidative stress, steroidogenic suppression, and modulation by ZnO-NP/TEO synergy","authors":"Asmaa S. Morsi , Hager M. Ramadan , Ahmed M. Youssef , Nadia A. Taha","doi":"10.1016/j.fct.2025.115675","DOIUrl":null,"url":null,"abstract":"<div><div>Potassium dichromate (PDC), a potent industrial toxicant, induces severe testicular damage, though its precise mechanisms remain incompletely defined. This study investigated the mechanistic pathways of PDC-induced reproductive toxicity in male Sprague-Dawley rats (n = 108). Rats were allocated into 9 groups: controls (oral, intraperitoneal) <strong>(I),(II), PDC</strong>-only (10.5 mg/kg bwt, <strong>III)</strong>, Zinc Oxide Nanoparticles, <strong>ZnO-NPs</strong>-only (5 mg/kg bwt, <strong>IV</strong>), Thyme Essential Oil, <strong>TEO</strong>-only (5 mg/kg bwt, <strong>V)</strong>, <strong>ZnO-NPs + TEO (VI)</strong>, <strong>PDC + ZnO-NPs (VII)</strong>, <strong>PDC + TEO (VIII)</strong>, and <strong>PDC + ZnO-NPs + TEO (IX)</strong>, treated for 8 weeks. <strong>PDC</strong> exposure triggered significant testicular oxidative stress, evidenced by elevated malondialdehyde <strong>(MDA)</strong> and Nitric oxide <strong>(Nox)</strong> activity alongside depleted catalase, glutathione, and total antioxidants. This redox imbalance directly correlated with impaired spermatogenesis and steroidogenesis, manifesting as reduced testis weight, decreased serum free testosterone, LH, and FSH levels, compromised sperm quality (motility, count, morphology), and downregulation steroidogenic genes <strong>(<em>StAR</em>, <em>CYP11A1</em>, HSD-3β)</strong>. Histopathological analysis confirmed seminiferous tubule degeneration and germ cell apoptosis. Critically, reversal of these effects by antioxidants <strong>(TEO, ZnO-NPs;</strong> alone/combined) <strong>validated oxidative stress and steroidogenic disruption as primary drivers of PDC testicular toxicity</strong>. These findings define the mechanistic basis of <strong>PDC-</strong>induced reproductive injury, highlighting its disruption of redox balance and endocrine function.</div></div>","PeriodicalId":317,"journal":{"name":"Food and Chemical Toxicology","volume":"204 ","pages":"Article 115675"},"PeriodicalIF":3.5000,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Food and Chemical Toxicology","FirstCategoryId":"97","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0278691525004430","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"FOOD SCIENCE & TECHNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Potassium dichromate (PDC), a potent industrial toxicant, induces severe testicular damage, though its precise mechanisms remain incompletely defined. This study investigated the mechanistic pathways of PDC-induced reproductive toxicity in male Sprague-Dawley rats (n = 108). Rats were allocated into 9 groups: controls (oral, intraperitoneal) (I),(II), PDC-only (10.5 mg/kg bwt, III), Zinc Oxide Nanoparticles, ZnO-NPs-only (5 mg/kg bwt, IV), Thyme Essential Oil, TEO-only (5 mg/kg bwt, V), ZnO-NPs + TEO (VI), PDC + ZnO-NPs (VII), PDC + TEO (VIII), and PDC + ZnO-NPs + TEO (IX), treated for 8 weeks. PDC exposure triggered significant testicular oxidative stress, evidenced by elevated malondialdehyde (MDA) and Nitric oxide (Nox) activity alongside depleted catalase, glutathione, and total antioxidants. This redox imbalance directly correlated with impaired spermatogenesis and steroidogenesis, manifesting as reduced testis weight, decreased serum free testosterone, LH, and FSH levels, compromised sperm quality (motility, count, morphology), and downregulation steroidogenic genes (StAR, CYP11A1, HSD-3β). Histopathological analysis confirmed seminiferous tubule degeneration and germ cell apoptosis. Critically, reversal of these effects by antioxidants (TEO, ZnO-NPs; alone/combined) validated oxidative stress and steroidogenic disruption as primary drivers of PDC testicular toxicity. These findings define the mechanistic basis of PDC-induced reproductive injury, highlighting its disruption of redox balance and endocrine function.
期刊介绍:
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.