Amifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility status

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dc.contributor.authorVendramini, Vanessa
dc.contributor.authorCerri, Estela Sasso [UNESP]
dc.contributor.authorMiraglia, Sandra M.
dc.contributor.institutionUniversidade de São Paulo (USP)
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.date.accessioned2014-05-27T11:24:37Z
dc.date.available2014-05-27T11:24:37Z
dc.date.issued2010-01-10
dc.description.abstractBackground: 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.en
dc.description.affiliationDevelopmental Biology Laboratory Department of Morphology and Genetics Federal University of São Paulo (UNIFESP), São Paulo-SP
dc.description.affiliationLaboratory of Histology and Embryology Department of Morphology Dental School of São Paulo State University (UNESP), Araraquara-SP
dc.description.affiliationUnespLaboratory of Histology and Embryology Department of Morphology Dental School of São Paulo State University (UNESP), Araraquara-SP
dc.identifierhttp://dx.doi.org/10.1186/1477-7827-8-3
dc.identifier.citationReproductive Biology and Endocrinology, v. 8.
dc.identifier.doi10.1186/1477-7827-8-3
dc.identifier.file2-s2.0-77949608514.pdf
dc.identifier.issn1477-7827
dc.identifier.lattes4455630076841302
dc.identifier.scopus2-s2.0-77949608514
dc.identifier.urihttp://hdl.handle.net/11449/71564
dc.language.isoeng
dc.relation.ispartofReproductive Biology and Endocrinology
dc.relation.ispartofjcr2.852
dc.relation.ispartofsjr1,203
dc.rights.accessRightsAcesso aberto
dc.sourceScopus
dc.subjectamifostine
dc.subjectDNA
dc.subjectdoxorubicin
dc.subjectsodium chloride
dc.subjectantineoplastic antibiotic
dc.subjectradioprotective agent
dc.subjectanimal cell
dc.subjectanimal experiment
dc.subjectanimal model
dc.subjectanimal tissue
dc.subjectcell differentiation
dc.subjectcell protection
dc.subjectcontrolled study
dc.subjectDNA content
dc.subjectDNA damage
dc.subjectDNA determination
dc.subjectepididymis
dc.subjectfemale
dc.subjectmale
dc.subjectmale fertility
dc.subjectmating
dc.subjectmicroscopy
dc.subjectmorphometrics
dc.subjectnonhuman
dc.subjectprepuberty
dc.subjectrat
dc.subjectreproduction
dc.subjectsemen abnormality
dc.subjectseminiferous tubule epithelium
dc.subjectspermatogonium
dc.subjectspermatozoon count
dc.subjectspermatozoon motility
dc.subjecttestis injury
dc.subjectanimal
dc.subjectchemically induced disorder
dc.subjectdown regulation
dc.subjectdrug effect
dc.subjectevaluation
dc.subjectfertility
dc.subjecthealth status
dc.subjectpathology
dc.subjectphysiology
dc.subjectpregnancy
dc.subjectsemen analysis
dc.subjectsexual maturation
dc.subjecttestis disease
dc.subjectWistar rat
dc.subjectAnimalia
dc.subjectRattus
dc.subjectAmifostine
dc.subjectAnimals
dc.subjectAntibiotics, Antineoplastic
dc.subjectCytoprotection
dc.subjectDown-Regulation
dc.subjectDoxorubicin
dc.subjectFemale
dc.subjectFertility
dc.subjectHealth Status
dc.subjectMale
dc.subjectPregnancy
dc.subjectRadiation-Protective Agents
dc.subjectRats
dc.subjectRats, Wistar
dc.subjectSemen Analysis
dc.subjectSeminiferous Epithelium
dc.subjectSexual Maturation
dc.subjectTesticular Diseases
dc.titleAmifostine reduces the seminiferous epithelium damage in doxorubicin-treated prepubertal rats without improving the fertility statusen
dc.typeArtigo
dcterms.licensehttp://www.biomedcentral.com/about/license
unesp.author.lattes4455630076841302
unesp.campusUniversidade Estadual Paulista (Unesp), Faculdade de Odontologia, Araraquarapt

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