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地拉罗司,一种铁螯合剂,可改善精索静脉曲张大鼠模型的睾丸形态计量和精子功能参数。

Deferasirox, an Iron-Chelating Agent, Improves Testicular Morphometric and Sperm Functional Parameters in a Rat Model of Varicocele.

机构信息

Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran.

Department of Basic Science, School of Veterinary Medicine, Shahid Bahonar University of Kerman, Kerman, Iran.

出版信息

Oxid Med Cell Longev. 2021 Apr 8;2021:6698482. doi: 10.1155/2021/6698482. eCollection 2021.

DOI:10.1155/2021/6698482
PMID:33897943
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8052147/
Abstract

Varicocele is characterized by testicular dysfunction that originates from hyperthermia and hypoxia, leading to defects in testicular tissue and altered spermatozoa structure and function. The varicocele testis is characterized by the presence of intracellular iron deposits that contribute to the associated oxidative stress. Therefore, we tested the hypothesis that administration of an iron-chelating agent, such as deferasirox (DFX), could potentially mitigate the consequences of varicocele on testicular tissue and spermatozoa. Using a well-established rat model of varicocele (VCL), we show that treatment with DFX partially improved the structure and function of the testis and spermatozoa. In particular, sperm motility was markedly restored whereas abnormal sperm morphology was only partially improved. No significant improvement in sperm count was observed that could be associated with the proapoptotic response observed following iron chelation treatment. No reduction in oxidative damage to spermatozoa was observed since lipid peroxidation and DNA integrity were not modified. This was suggested to be a result of increased oxidative stress. Finally, we also saw no indication of attenuation of the endoplasmic reticulum/unfolded protein (ER/UPR) stress response that we recently found associated with the VCL testis in rats.

摘要

精索静脉曲张的特征是睾丸功能障碍,其源于高温和缺氧,导致睾丸组织缺陷以及精子结构和功能改变。精索静脉曲张睾丸的特征是存在细胞内铁沉积,这有助于相关的氧化应激。因此,我们检验了这样一个假设,即给予铁螯合剂(如地拉罗司)可能会减轻精索静脉曲张对睾丸组织和精子的影响。我们使用已建立的精索静脉曲张大鼠模型(VCL),表明地拉罗司治疗可部分改善睾丸和精子的结构和功能。特别是,精子运动能力显著恢复,而精子形态异常仅部分改善。未观察到精子计数的显著改善,这可能与铁螯合治疗后观察到的促凋亡反应有关。由于未改变精子的脂质过氧化和 DNA 完整性,因此未观察到对精子的氧化损伤的减少。这被认为是氧化应激增加的结果。最后,我们也没有发现内质网/未折叠蛋白(ER/UPR)应激反应的减弱迹象,我们最近发现该反应与大鼠的 VCL 睾丸有关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/a989049c5e8e/OMCL2021-6698482.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/98fe2aa47762/OMCL2021-6698482.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/80da09058863/OMCL2021-6698482.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/f7a35113f5ee/OMCL2021-6698482.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/032d870fba06/OMCL2021-6698482.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/39a3c26c2a48/OMCL2021-6698482.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/a989049c5e8e/OMCL2021-6698482.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/98fe2aa47762/OMCL2021-6698482.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/80da09058863/OMCL2021-6698482.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/f7a35113f5ee/OMCL2021-6698482.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/032d870fba06/OMCL2021-6698482.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/39a3c26c2a48/OMCL2021-6698482.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2419/8052147/a989049c5e8e/OMCL2021-6698482.006.jpg

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