The Effect of Vitamin D3 supplementation on Flunitrazepam-Induced testicular dysfunction in Wistar rats

IF 2.1 4区医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Steroids Pub Date : 2025-06-14 DOI:10.1016/j.steroids.2025.109650

David Tolulope Oluwole , Aliyah Ochuwa Yakubu , Oladipupo Samuel Ebiwonjumi , Lydia Oluwatoyin Ajayi , Ayodeji Folorunsho Ajayi

{"title":"The Effect of Vitamin D3 supplementation on Flunitrazepam-Induced testicular dysfunction in Wistar rats","authors":"David Tolulope Oluwole , Aliyah Ochuwa Yakubu , Oladipupo Samuel Ebiwonjumi , Lydia Oluwatoyin Ajayi , Ayodeji Folorunsho Ajayi","doi":"10.1016/j.steroids.2025.109650","DOIUrl":null,"url":null,"abstract":"<div><div>Prolonged flunitrazepam use has been reported to be increasing among young adolescents, and it has been reported to induce hyperprolactinemia, causing gross impairment of testicular function, ultimately resulting in male infertility. Hence, this current study seeks to examine the possible protective potential of the micronutrient Vitamin D3 in mitigating flunitrazepam-induced testicular dysfunction.</div><div>Adult male rats (Wistar strain), weighing 200–220 g, were categorized into four groups: Vehicle [0.3 ml of distilled water and 0.2 ml of olive oil, the respective solvents for flunitrazepam (Fluni) and Vitamin D3 (V.D3)], Fluni [0.35 mg/kg], V.D3 [0.01 mg/kg], and Fluni [0.35 mg/kg] + V.D3 [0.01 mg/kg]; these groups were treated orally for 56 days before the testes and epididymides were removed for biochemical and histological processing.</div><div>Vitamin D3 supplementation significantly prevented hyperprolactinemia and sperm cell damage, reduced testicular lipid peroxidation, and significantly increased serum concentrations of reproductive hormones, testicular steroidogenic enzymes, antioxidants, and improved inflammatory markers. It also improved sperm energy utilization, quality, and transmembrane pump activities, with a marked recovery of the epididymal smooth muscles and testicular interstitial and spermatogonial cells in the flunitrazepam-treated rats.</div><div>This present study shows that Vitamin D3 supplementation prevents impairment of testicular functions and ensures improved sperm function in flunitrazepam-exposed rats. Meanwhile, further molecular studies and clinical trials are encouraged to explore Vitamin D3′s possible intervention in drug-induced male infertility, given the limitations of animal studies.</div></div>","PeriodicalId":21997,"journal":{"name":"Steroids","volume":"221 ","pages":"Article 109650"},"PeriodicalIF":2.1000,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Steroids","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0039128X25000911","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Prolonged flunitrazepam use has been reported to be increasing among young adolescents, and it has been reported to induce hyperprolactinemia, causing gross impairment of testicular function, ultimately resulting in male infertility. Hence, this current study seeks to examine the possible protective potential of the micronutrient Vitamin D3 in mitigating flunitrazepam-induced testicular dysfunction.

Adult male rats (Wistar strain), weighing 200–220 g, were categorized into four groups: Vehicle [0.3 ml of distilled water and 0.2 ml of olive oil, the respective solvents for flunitrazepam (Fluni) and Vitamin D3 (V.D3)], Fluni [0.35 mg/kg], V.D3 [0.01 mg/kg], and Fluni [0.35 mg/kg] + V.D3 [0.01 mg/kg]; these groups were treated orally for 56 days before the testes and epididymides were removed for biochemical and histological processing.

Vitamin D3 supplementation significantly prevented hyperprolactinemia and sperm cell damage, reduced testicular lipid peroxidation, and significantly increased serum concentrations of reproductive hormones, testicular steroidogenic enzymes, antioxidants, and improved inflammatory markers. It also improved sperm energy utilization, quality, and transmembrane pump activities, with a marked recovery of the epididymal smooth muscles and testicular interstitial and spermatogonial cells in the flunitrazepam-treated rats.

This present study shows that Vitamin D3 supplementation prevents impairment of testicular functions and ensures improved sperm function in flunitrazepam-exposed rats. Meanwhile, further molecular studies and clinical trials are encouraged to explore Vitamin D3′s possible intervention in drug-induced male infertility, given the limitations of animal studies.

查看原文本刊更多论文

补充维生素D3对氟硝西泮致Wistar大鼠睾丸功能障碍的影响

据报道，青少年长期使用氟硝西泮的情况越来越多，据报道，氟硝西泮可诱发高泌乳素血症，严重损害睾丸功能，最终导致男性不育。因此，本研究旨在研究微量营养素维生素D3在减轻氟硝西泮引起的睾丸功能障碍中的可能保护潜力。体重200 ~ 220 g的Wistar品系成年雄性大鼠分为4组：对照剂[0.3 ml蒸馏水和0.2 ml橄榄油，分别为氟硝西泮（Fluni）和维生素D3 （V.D3）的溶剂]、Fluni [0.35 mg/kg]、V.D3 [0.01 mg/kg]和Fluni [0.35 mg/kg] + V.D3 [0.01 mg/kg]；各组小鼠口服治疗56 d后，切除睾丸和附睾进行生化和组织学处理。补充维生素D3可显著预防高泌乳素血症和精子细胞损伤，减少睾丸脂质过氧化，显著提高血清生殖激素、睾丸甾体生成酶、抗氧化剂浓度，改善炎症标志物。氟硝西泮治疗大鼠的附睾平滑肌、睾丸间质细胞和精原细胞明显恢复，提高了精子能量利用、质量和跨膜泵活性。本研究表明，在氟硝西泮暴露的大鼠中，补充维生素D3可以防止睾丸功能受损，并确保改善精子功能。同时，鉴于动物研究的局限性，鼓励进一步的分子研究和临床试验来探索维生素D3对药物性男性不育症的可能干预。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Steroids 医学-内分泌学与代谢

CiteScore

5.10

自引率

3.70%

发文量

120

审稿时长

73 days

期刊介绍： STEROIDS is an international research journal devoted to studies on all chemical and biological aspects of steroidal moieties. The journal focuses on both experimental and theoretical studies on the biology, chemistry, biosynthesis, metabolism, molecular biology, physiology and pharmacology of steroids and other molecules that target or regulate steroid receptors. Manuscripts presenting clinical research related to steroids, steroid drug development, comparative endocrinology of steroid hormones, investigations on the mechanism of steroid action and steroid chemistry are all appropriate for submission for peer review. STEROIDS publishes both original research and timely reviews. For details concerning the preparation of manuscripts see Instructions to Authors, which is published in each issue of the journal.