Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNESP |
Texto Completo: | http://dx.doi.org/10.1186/1477-7827-8-3 http://hdl.handle.net/11449/71564 |
Resumo: | Background: Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out.Methods: Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). Standard One Way Anova parametric and Anova on Ranks non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05.Results: The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration.Conclusions: These results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models. © 2010 Vendramini et al; licensee BioMed Central Ltd. |
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Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility statusamifostineDNAdoxorubicinsodium chlorideantineoplastic antibioticradioprotective agentanimal cellanimal experimentanimal modelanimal tissuecell differentiationcell protectioncontrolled studyDNA contentDNA damageDNA determinationepididymisfemalemalemale fertilitymatingmicroscopymorphometricsnonhumanprepubertyratreproductionsemen abnormalityseminiferous tubule epitheliumspermatogoniumspermatozoon countspermatozoon motilitytestis injuryanimalchemically induced disorderdown regulationdrug effectevaluationfertilityhealth statuspathologyphysiologypregnancysemen analysissexual maturationtestis diseaseWistar ratAnimaliaRattusAmifostineAnimalsAntibiotics, AntineoplasticCytoprotectionDown-RegulationDoxorubicinFemaleFertilityHealth StatusMalePregnancyRadiation-Protective AgentsRatsRats, WistarSemen AnalysisSeminiferous EpitheliumSexual MaturationTesticular DiseasesBackground: Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out.Methods: Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). Standard One Way Anova parametric and Anova on Ranks non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05.Results: The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration.Conclusions: These results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models. © 2010 Vendramini et al; licensee BioMed Central Ltd.Developmental Biology Laboratory Department of Morphology and Genetics Federal University of São Paulo (UNIFESP), São Paulo-SPLaboratory of Histology and Embryology Department of Morphology Dental School of São Paulo State University (UNESP), Araraquara-SPLaboratory of Histology and Embryology Department of Morphology Dental School of São Paulo State University (UNESP), Araraquara-SPUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Vendramini, VanessaCerri, Estela Sasso [UNESP]Miraglia, Sandra M.2014-05-27T11:24:37Z2014-05-27T11:24:37Z2010-01-10info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://dx.doi.org/10.1186/1477-7827-8-3Reproductive Biology and Endocrinology, v. 8.1477-7827http://hdl.handle.net/11449/7156410.1186/1477-7827-8-32-s2.0-779496085142-s2.0-77949608514.pdf4455630076841302Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengReproductive Biology and Endocrinology2.8521,203info:eu-repo/semantics/openAccess2023-11-03T06:08:25Zoai:repositorio.unesp.br:11449/71564Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T16:47:39.852746Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false |
dc.title.none.fl_str_mv |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
title |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
spellingShingle |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status Vendramini, Vanessa amifostine DNA doxorubicin sodium chloride antineoplastic antibiotic radioprotective agent animal cell animal experiment animal model animal tissue cell differentiation cell protection controlled study DNA content DNA damage DNA determination epididymis female male male fertility mating microscopy morphometrics nonhuman prepuberty rat reproduction semen abnormality seminiferous tubule epithelium spermatogonium spermatozoon count spermatozoon motility testis injury animal chemically induced disorder down regulation drug effect evaluation fertility health status pathology physiology pregnancy semen analysis sexual maturation testis disease Wistar rat Animalia Rattus Amifostine Animals Antibiotics, Antineoplastic Cytoprotection Down-Regulation Doxorubicin Female Fertility Health Status Male Pregnancy Radiation-Protective Agents Rats Rats, Wistar Semen Analysis Seminiferous Epithelium Sexual Maturation Testicular Diseases |
title_short |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
title_full |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
title_fullStr |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
title_full_unstemmed |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
title_sort |
Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status |
author |
Vendramini, Vanessa |
author_facet |
Vendramini, Vanessa Cerri, Estela Sasso [UNESP] Miraglia, Sandra M. |
author_role |
author |
author2 |
Cerri, Estela Sasso [UNESP] Miraglia, Sandra M. |
author2_role |
author author |
dc.contributor.none.fl_str_mv |
Universidade de São Paulo (USP) Universidade Estadual Paulista (Unesp) |
dc.contributor.author.fl_str_mv |
Vendramini, Vanessa Cerri, Estela Sasso [UNESP] Miraglia, Sandra M. |
dc.subject.por.fl_str_mv |
amifostine DNA doxorubicin sodium chloride antineoplastic antibiotic radioprotective agent animal cell animal experiment animal model animal tissue cell differentiation cell protection controlled study DNA content DNA damage DNA determination epididymis female male male fertility mating microscopy morphometrics nonhuman prepuberty rat reproduction semen abnormality seminiferous tubule epithelium spermatogonium spermatozoon count spermatozoon motility testis injury animal chemically induced disorder down regulation drug effect evaluation fertility health status pathology physiology pregnancy semen analysis sexual maturation testis disease Wistar rat Animalia Rattus Amifostine Animals Antibiotics, Antineoplastic Cytoprotection Down-Regulation Doxorubicin Female Fertility Health Status Male Pregnancy Radiation-Protective Agents Rats Rats, Wistar Semen Analysis Seminiferous Epithelium Sexual Maturation Testicular Diseases |
topic |
amifostine DNA doxorubicin sodium chloride antineoplastic antibiotic radioprotective agent animal cell animal experiment animal model animal tissue cell differentiation cell protection controlled study DNA content DNA damage DNA determination epididymis female male male fertility mating microscopy morphometrics nonhuman prepuberty rat reproduction semen abnormality seminiferous tubule epithelium spermatogonium spermatozoon count spermatozoon motility testis injury animal chemically induced disorder down regulation drug effect evaluation fertility health status pathology physiology pregnancy semen analysis sexual maturation testis disease Wistar rat Animalia Rattus Amifostine Animals Antibiotics, Antineoplastic Cytoprotection Down-Regulation Doxorubicin Female Fertility Health Status Male Pregnancy Radiation-Protective Agents Rats Rats, Wistar Semen Analysis Seminiferous Epithelium Sexual Maturation Testicular Diseases |
description |
Background: Amifostine is an efficient cytoprotector against toxicity caused by some chemotherapeutic drugs. Doxorubicin, a potent anticancer anthracycline, is known to produce spermatogenic damage even in low doses. Although some studies have suggested that amifostine does not confer protection to doxorubicin-induced testicular damage, schedules and age of treatment have different approach depending on the protocol. Thus, we proposed to investigate the potential cytoprotective action of amifostine against the damage provoked by doxorubicin to prepubertal rat testes (30-day-old) by assessing some macro and microscopic morphometric parameters 15, 30 and 60 days after the treatment; for fertility evaluation, quantitative analyses of sperm parameters and reproductive competence in the adult phase were also carried out.Methods: Thirty-day-old male rats were distributed into four groups: Doxorubicin (5 mg/kg), Amifostine (400 mg/kg), Amifostine/Doxorubicin (amifostine 15 minutes before doxorubicin) and Sham Control (0.9% saline solution). Standard One Way Anova parametric and Anova on Ranks non-parametric tests were applied according to the behavior of the obtained data; significant differences were considered when p < 0.05.Results: The rats killed 30 and 60 days after doxorubicin treatment showed diminution of seminiferous epithelium height and reduction on the frequency of tubular sections containing at least one type of differentiated spermatogonia; reduction of sperm concentration and motility and an increase of sperm anomalous forms where observed in doxorubicin-treated animals. All these parameters were improved in the Amifostine/Doxorubicin group only when compared to Doxorubicin group. Such reduction, however, still remained below the values obtained from the Sham Control group. Nevertheless, the reproductive competence of doxorubicin-treated rats was not improved by amifostine pre-administration.Conclusions: These results suggest that amifostine promotes a significant reduction of the doxorubicin long-term side effects on the seminiferous epithelium of prepubertal rats, which is reflected in the epidydimal fluid parameters in the adult phase. However, fertility status results suggest that such protection may not be effective against sperm DNA content damage. Further investigation of sperm DNA integrity must be carried out using amifostine and doxorubicin-treated experimental models. © 2010 Vendramini et al; licensee BioMed Central Ltd. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010-01-10 2014-05-27T11:24:37Z 2014-05-27T11:24:37Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://dx.doi.org/10.1186/1477-7827-8-3 Reproductive Biology and Endocrinology, v. 8. 1477-7827 http://hdl.handle.net/11449/71564 10.1186/1477-7827-8-3 2-s2.0-77949608514 2-s2.0-77949608514.pdf 4455630076841302 |
url |
http://dx.doi.org/10.1186/1477-7827-8-3 http://hdl.handle.net/11449/71564 |
identifier_str_mv |
Reproductive Biology and Endocrinology, v. 8. 1477-7827 10.1186/1477-7827-8-3 2-s2.0-77949608514 2-s2.0-77949608514.pdf 4455630076841302 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
Reproductive Biology and Endocrinology 2.852 1,203 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.source.none.fl_str_mv |
Scopus reponame:Repositório Institucional da UNESP instname:Universidade Estadual Paulista (UNESP) instacron:UNESP |
instname_str |
Universidade Estadual Paulista (UNESP) |
instacron_str |
UNESP |
institution |
UNESP |
reponame_str |
Repositório Institucional da UNESP |
collection |
Repositório Institucional da UNESP |
repository.name.fl_str_mv |
Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP) |
repository.mail.fl_str_mv |
|
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1808128702036312064 |