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Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice

The alkylating antineoplastic agent cyclophosphamide (CP) is known to be toxic to the male reproductive system, but there are no effective prevention or treatment options. The flavonoid icariin (ICA), which is used in Chinese medicine, has been shown to have a number of biological functions, includi...

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Autores principales: Fang, Chunyan, Ye, Yulong, Yang, Fang, Wang, Fangyue, Shen, Yifeng, Chang, Degui, You, Yaodong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794755/
https://www.ncbi.nlm.nih.gov/pubmed/36588705
http://dx.doi.org/10.3389/fphar.2022.1040544
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author Fang, Chunyan
Ye, Yulong
Yang, Fang
Wang, Fangyue
Shen, Yifeng
Chang, Degui
You, Yaodong
author_facet Fang, Chunyan
Ye, Yulong
Yang, Fang
Wang, Fangyue
Shen, Yifeng
Chang, Degui
You, Yaodong
author_sort Fang, Chunyan
collection PubMed
description The alkylating antineoplastic agent cyclophosphamide (CP) is known to be toxic to the male reproductive system, but there are no effective prevention or treatment options. The flavonoid icariin (ICA), which is used in Chinese medicine, has been shown to have a number of biological functions, including testicular protection. The current study looked into the protective effects of ICA in preventing CP-induced spermatogenesis dysfunction. The current study looked into the role of ICA in preventing testicular dysfunction caused by CP. For 5 days, healthy adult mice were given saline or a single dose of CP (50 mg/kg) intraperitoneally (i.p). For the next 30 days, mice were given ICA (80 mg/kg) by gavage. Animals were euthanized 12 h after receiving ICA, and testes were removed for biochemical, histopathological, sperm evaluation, and transmission electron microscope analysis (TEM). We also investigated the potential biological effects of ICA on CP-induced spermatogenesis dysfunction in mice using an integrated proteomic and metabolomic approach. The levels of 8309 proteins and 600 metabolites were measured. The majority of the differential proteins and metabolites were found to be enriched in a variety of metabolic pathways, including the PI3K-Akt signaling pathway, necroptosis, the mTOR signaling pathway, glycerophospholipid metabolism, and ABC transporters, implying that ICA may have molecular mechanisms that contribute to CP-induced spermatogenesis dysfunction in the testis. Taken together, these findings show that ICA effectively reduces testis injury, implying that ICA may have a role in male infertility preservation.
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spelling pubmed-97947552022-12-29 Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice Fang, Chunyan Ye, Yulong Yang, Fang Wang, Fangyue Shen, Yifeng Chang, Degui You, Yaodong Front Pharmacol Pharmacology The alkylating antineoplastic agent cyclophosphamide (CP) is known to be toxic to the male reproductive system, but there are no effective prevention or treatment options. The flavonoid icariin (ICA), which is used in Chinese medicine, has been shown to have a number of biological functions, including testicular protection. The current study looked into the protective effects of ICA in preventing CP-induced spermatogenesis dysfunction. The current study looked into the role of ICA in preventing testicular dysfunction caused by CP. For 5 days, healthy adult mice were given saline or a single dose of CP (50 mg/kg) intraperitoneally (i.p). For the next 30 days, mice were given ICA (80 mg/kg) by gavage. Animals were euthanized 12 h after receiving ICA, and testes were removed for biochemical, histopathological, sperm evaluation, and transmission electron microscope analysis (TEM). We also investigated the potential biological effects of ICA on CP-induced spermatogenesis dysfunction in mice using an integrated proteomic and metabolomic approach. The levels of 8309 proteins and 600 metabolites were measured. The majority of the differential proteins and metabolites were found to be enriched in a variety of metabolic pathways, including the PI3K-Akt signaling pathway, necroptosis, the mTOR signaling pathway, glycerophospholipid metabolism, and ABC transporters, implying that ICA may have molecular mechanisms that contribute to CP-induced spermatogenesis dysfunction in the testis. Taken together, these findings show that ICA effectively reduces testis injury, implying that ICA may have a role in male infertility preservation. Frontiers Media S.A. 2022-12-14 /pmc/articles/PMC9794755/ /pubmed/36588705 http://dx.doi.org/10.3389/fphar.2022.1040544 Text en Copyright © 2022 Fang, Ye, Yang, Wang, Shen, Chang and You. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Fang, Chunyan
Ye, Yulong
Yang, Fang
Wang, Fangyue
Shen, Yifeng
Chang, Degui
You, Yaodong
Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
title Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
title_full Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
title_fullStr Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
title_full_unstemmed Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
title_short Integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
title_sort integrative proteomics and metabolomics approach to identify the key roles of icariin-mediated protective effects against cyclophosphamide-induced spermatogenesis dysfunction in mice
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9794755/
https://www.ncbi.nlm.nih.gov/pubmed/36588705
http://dx.doi.org/10.3389/fphar.2022.1040544
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