RESUMO
Vitamin A and its derivatives contribute to many physiological processes, including vision, neural differentiation, and reproduction. Vitamin A deficiency causes early cessation of spermatogenesis, characterized by a marked depletion of germ cells. However, there has been no clear understanding about the role of chronic intake of vitamin A excess (VAE) in spermatogenesis. The objective of this study was to investigate whether chronic intake of VAE diet causes arrest of spermatogenesis. To examine the effects of VAE on spermatogenesis, we used ICR male mice fed with control (AIN-93G purified diet: 4 IU/g) diet or VAE (modified AIN-93G diet with VAE: 1,000 IU/g) diet for 7 weeks (from 3 to 10 weeks of age). At 10 weeks of age, the retinol concentration in the testes of VAE mice was significantly higher than that of control mice. Testicular cross sections from control mice contained a normal array of germ cells, while the seminiferous tubules from VAE mice exhibited varying degrees of testicular degeneration. Daily sperm production in VAE testes was dramatically decreased compared to that in control testes. Sperm viability, motility, and morphology were also impaired in VAE mice. Furthermore, we examined the effects of VAE on the expression of genes involved in retinoid signaling and spermatogenesis to determine the underlying molecular mechanisms. Therefore, we are the first to present results describing the long-term dietary intake of VAE impairs spermatogenesis using a mouse model.
Assuntos
Exposição Dietética/efeitos adversos , Hipervitaminose A/etiologia , Hipervitaminose A/fisiopatologia , Espermatogênese/efeitos dos fármacos , Vitamina A/administração & dosagem , Vitamina A/efeitos adversos , Animais , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Hipervitaminose A/metabolismo , Masculino , Camundongos Endogâmicos ICR , Gravidez , Retinoides , Transdução de Sinais/genética , Motilidade dos Espermatozoides/efeitos dos fármacos , Espermatogênese/genética , Espermatozoides/efeitos dos fármacos , Espermatozoides/patologia , Testículo/efeitos dos fármacos , Testículo/metabolismo , Testículo/patologia , Fatores de Tempo , Vitamina A/metabolismoRESUMO
Dexrazoxane(DXZ)is a drug used for treating extravasation(EV)of anthracycline antitumor antibiotics based on 2 of its mechanisms of action through Topo II. In Japan, it has been used in approximately 150 patients as of January 2016, but there is no detailed report. Three DXZ treatments were carried out for 2 cases in our facilities. One case involved a patient's right forearm while 2 cases occurred involved the left and right forearms of each of the patients, and both were Grade 2(CTCAE v4.0). The EV healed in all cases, and surgical procedures were not needed. Moreover, chemotherapy was performed without extending the treatment period. One year 8 months after administration there was no recurrence in both cases, and skin disorders did not develop. In our hospital, DXZ is managed based on the regimen as well as the anticancer agents, and administration within 6 hours from extravasation was made possible by the cooperation of pharmaceutical wholesalers. Nurses and pharmacists who engage in chemotherapy are encouraged to participate in the study sessions of the hospital, it has been the effort to learn the day-to-day knowledge and technology. DXZ is effective in treating the EV of anthracycline antitumor antibiotics and may be well tolerated. To properly use DXZ by integrating these cases, it is necessary to verify its effectiveness and safety.
