Cargando…
Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms
Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radio...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002482/ https://www.ncbi.nlm.nih.gov/pubmed/33802807 http://dx.doi.org/10.3390/molecules26061676 |
_version_ | 1783671473932599296 |
---|---|
author | Rossi, Giulia Placidi, Martina Castellini, Chiara Rea, Francesco D'Andrea, Settimio Alonso, Gonzalo Luis Gravina, Giovanni Luca Tatone, Carla Di Emidio, Giovanna D’Alessandro, Anna Maria |
author_facet | Rossi, Giulia Placidi, Martina Castellini, Chiara Rea, Francesco D'Andrea, Settimio Alonso, Gonzalo Luis Gravina, Giovanni Luca Tatone, Carla Di Emidio, Giovanna D’Alessandro, Anna Maria |
author_sort | Rossi, Giulia |
collection | PubMed |
description | Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period. |
format | Online Article Text |
id | pubmed-8002482 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-80024822021-03-28 Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms Rossi, Giulia Placidi, Martina Castellini, Chiara Rea, Francesco D'Andrea, Settimio Alonso, Gonzalo Luis Gravina, Giovanni Luca Tatone, Carla Di Emidio, Giovanna D’Alessandro, Anna Maria Molecules Article Infertility is a potential side effect of radiotherapy and significantly affects the quality of life for adolescent cancer survivors. Very few studies have addressed in pubertal models the mechanistic events that could be targeted to provide protection from gonadotoxicity and data on potential radioprotective treatments in this peculiar period of life are elusive. In this study, we utilized an in vitro model of the mouse pubertal testis to investigate the efficacy of crocetin to counteract ionizing radiation (IR)-induced injury and potential underlying mechanisms. Present experiments provide evidence that exposure of testis fragments from pubertal mice to 2 Gy X-rays induced extensive structural and cellular damage associated with overexpression of PARP1, PCNA, SOD2 and HuR and decreased levels of SIRT1 and catalase. A twenty-four hr exposure to 50 μM crocetin pre- and post-IR significantly reduced testis injury and modulated the response to DNA damage and oxidative stress. Nevertheless, crocetin treatment did not counteract the radiation-induced changes in the expression of SIRT1, p62 and LC3II. These results increase the knowledge of mechanisms underlying radiation damage in pubertal testis and establish the use of crocetin as a fertoprotective agent against IR deleterious effects in pubertal period. MDPI 2021-03-17 /pmc/articles/PMC8002482/ /pubmed/33802807 http://dx.doi.org/10.3390/molecules26061676 Text en © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Rossi, Giulia Placidi, Martina Castellini, Chiara Rea, Francesco D'Andrea, Settimio Alonso, Gonzalo Luis Gravina, Giovanni Luca Tatone, Carla Di Emidio, Giovanna D’Alessandro, Anna Maria Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms |
title | Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms |
title_full | Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms |
title_fullStr | Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms |
title_full_unstemmed | Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms |
title_short | Crocetin Mitigates Irradiation Injury in an In Vitro Model of the Pubertal Testis: Focus on Biological Effects and Molecular Mechanisms |
title_sort | crocetin mitigates irradiation injury in an in vitro model of the pubertal testis: focus on biological effects and molecular mechanisms |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8002482/ https://www.ncbi.nlm.nih.gov/pubmed/33802807 http://dx.doi.org/10.3390/molecules26061676 |
work_keys_str_mv | AT rossigiulia crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT placidimartina crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT castellinichiara crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT reafrancesco crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT dandreasettimio crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT alonsogonzaloluis crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT gravinagiovanniluca crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT tatonecarla crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT diemidiogiovanna crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms AT dalessandroannamaria crocetinmitigatesirradiationinjuryinaninvitromodelofthepubertaltestisfocusonbiologicaleffectsandmolecularmechanisms |