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在动物模型中给予替诺福韦纳米颗粒后睾丸的组织形态计量学变化。

Histomorphometric changes in testis following administration of tenofovir nanoparticles in an animal model.

作者信息

Naidu Edwin Coleridge, Olojede Samuel Oluwaseun, Lawal Sodiq Kolawole, Azu Onyemaechi Okpara

机构信息

Discipline of Clinical Anatomy, Nelson R. Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.

Department of Human Biology, Faculty of Health Sciences, Walter Sisulu University, Mthatha, 5117, South Africa.

出版信息

Discov Nano. 2024 Mar 25;19(1):56. doi: 10.1186/s11671-024-04002-y.

DOI:10.1186/s11671-024-04002-y
PMID:38526666
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10963688/
Abstract

BACKGROUND

Nanoparticle-based drugs are new inventions in the management of the Human immunodeficiency virus (HIV) pandemic, especially resistant forms of the virus in anatomical sanctuary sites and organs such as the testis. However, safety issues must be resolved to attain the optimal potential of newer nano-drug formulations.

AIM

The study investigated the toxicological potential of synthesized Tenofovir Nanoparticles (TDF-N) on testicular indices when used for the prevention and treatment of HIV.

METHODOLOGY

Fifteen male Sprague-Dawley (SD) rats with weight ranging from 230 g to 250 g were randomly assigned into groups A (control, saline), B (TDF), and C (TDF-N). The testes were removed for sperm analysis and processed for H/E and PAS stains. Cell counts and cellular measurements; the diameter and the area of the testicular seminiferous tubules were measured using ImageJ and Leica software 2.0.

RESULTS

A significant reduction (p < 0.05) in sperm count was noticed in the TDF-N group. Also observed in the TDF and TDF-N groups was a significant reduction (p < 0.05) in sperm motility and in the number of dead sperms compared with the control. Sperm abnormalities such as distorted basement membranes, loss of germ cells, hypocellular interstitium, and loss of spermatogenic series were increased in the TDF and TDF-N groups. There was also a significant reduction (p < 0.05) in the cell count, diameter, and area of seminiferous tubules observed in these groups.

CONCLUSION

TDF and TDF-N may be detrimental to the testis and testicular tissue, leading to significantly reduced sperm counts, motility, and ultimately-male fertility.

摘要

背景

基于纳米颗粒的药物是应对人类免疫缺陷病毒(HIV)大流行的新发明,特别是针对解剖学庇护部位(如睾丸)中病毒的耐药形式。然而,必须解决安全问题,以实现新型纳米药物制剂的最佳潜力。

目的

本研究调查了合成的替诺福韦纳米颗粒(TDF-N)用于预防和治疗HIV时对睾丸指标的毒理学潜力。

方法

将15只体重在230克至250克之间的雄性Sprague-Dawley(SD)大鼠随机分为A组(对照组,生理盐水)、B组(TDF组)和C组(TDF-N组)。取出睾丸进行精子分析,并进行苏木精/伊红(H/E)和过碘酸雪夫(PAS)染色。进行细胞计数和细胞测量;使用ImageJ和徕卡软件2.0测量睾丸生精小管的直径和面积。

结果

TDF-N组精子计数显著降低(p<0.05)。与对照组相比,TDF组和TDF-N组的精子活力和死精数量也显著降低(p<0.05)。TDF组和TDF-N组的精子异常情况增加,如基底膜扭曲、生殖细胞丢失、间质细胞减少和生精序列缺失。这些组的生精小管细胞计数、直径和面积也显著降低(p<0.05)。

结论

TDF和TDF-N可能对睾丸和睾丸组织有害,导致精子数量和活力显著降低,最终影响男性生育能力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/a4c3acef717c/11671_2024_4002_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/7f3e98d56697/11671_2024_4002_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/5409755f93b2/11671_2024_4002_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/f73bfd6665b3/11671_2024_4002_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/a4c3acef717c/11671_2024_4002_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/7f3e98d56697/11671_2024_4002_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/5409755f93b2/11671_2024_4002_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/f73bfd6665b3/11671_2024_4002_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/35c7/10963688/a4c3acef717c/11671_2024_4002_Fig4_HTML.jpg

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本文引用的文献

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Effect of dolutegravir-based first-line antiretroviral therapy on weight and body mass index among adult people living with HIV on follow up at health facilities in Hawassa city administration, Southern Ethiopia: a retrospective cohort study.基于多替拉韦的一线抗反转录病毒疗法对在埃塞俄比亚南部 Hawassa 市行政卫生机构接受随访的成年艾滋病毒感染者的体重和体重指数的影响:一项回顾性队列研究。
Ann Med. 2023;55(2):2242250. doi: 10.1080/07853890.2023.2242250.
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Tenofovir, Lamivudine, and Dolutegravir Among Rural Adolescents in Zimbabwe: A Cautionary Tale.津巴布韦农村青少年中使用替诺福韦、拉米夫定和度鲁特韦:一个警示故事。
AIDS Res Hum Retroviruses. 2022 Oct;38(10):774-778. doi: 10.1089/AID.2021.0140. Epub 2022 Sep 7.
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Int J Antimicrob Agents. 2022 Sep;60(3):106631. doi: 10.1016/j.ijantimicag.2022.106631. Epub 2022 Jul 1.
5
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