Carnitina reduz o estresse oxidativo em nível testicular e melhora a integridade do acrossoma e a fertilidade em ratos machos adultos, tratados com doxorrubicina na pré-puberdade

• Ano de defesa: 2016
• Autor(a) principal: Cabral, Regina Elizabeth Lourenço [UNIFESP]
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo (UNIFESP)
• Palavras-chave em Português: Carnitine; Doxorubicin; DNA; Fertility and spermatozoid; Carnitina; Doxorrubicina; Fertilidade e espermatozoide
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=4012850; http://repositorio.unifesp.br/handle/11600/46410

Doxorubicin has been widely used in anticancer therapy in adults, adolescents and children. The efficacy of L-carnitine as an antioxidant has already been confirmed both in clinical studies and experimental studies. Carnitine therapy has also been shown to be effective against male infertility. In a previous study, previous administration with L-carnitine in prepubertal rats could reduce the cytotoxicity caused by doxorubicin in the medium and long term, improving the testicular and sperm parameters of the animals analyzed. Objective: To evaluate whether qualitative sperm parameters, DNA integrity and sperm chromatin structure, as well as fertility and reproductive capacity of adult rats exposed to pre-pubertal doxorubicin can be improved by previous treatment with L-carnitine. METHODS: Forty-eight male pre-pubertal Wistar rats were divided into 4 groups, according to the type of treatment applied: Sham Control (SC, 0.9% physiological solution); Doxorubicin (Doxo, 5mg / kg, Pfeizer®); Carnitine (CA, 250mg / kg, Sigma); Carnitine / Doxorubicin (CAD, carnitine given at the same dose used for the CA group one hour before administration of doxorubicin - 5mg / kg). All treatments were administered Intraperitoneally and in a single dose in male rats at 30 days postpartum (DPP). At 100 DPP, the animals were separated into two sets. The animals of the first set were directed to sperm motility analysis (CASA, HTMIVOS), acrosome integrity, mitochondrial activity, sperm chromatin structure (SCSA) as well as evaluation of oxidative stress at testicular level (concentration of spermatozoa). Malondialdehyde and nitric oxide). The second set was used to evaluate fertility and reproductive capacity. Results: The percentage of spermatozoa with intact acrosome was higher in the Carnitine + Doxorubicin group when compared to that of the Doxorubicin group. However, sperm motility and mitochondrial activity did not improve with pre-treatment with Carnitine. The concentrations of malondialdehyde and nitric oxide were significantly higher in the Doxorubicin-only group compared to the Carnitine + Doxorubicin group. The fertility index and implantation index were markedly lower in the Doxorubicin group compared to the Carnitine + Doxorubicin group. In addition, the percentage of spermatozoa with damaged DNA was higher in the doxorubicin group when compared to the group Carnitine + Doxorubicin. Conclusion: Lcarnitine, when administered prior to Doxorubicin, partially preserves the integrity of the acrosome, an important feature related to sperm fertilization ability, which correlates positively with reproductive competence and sperm DNA integrity in adulthood. The results reinforce the importance of investigating several reproductive parameters in order to better evaluate and predict male reproductive potential.