This study examined whether the cytokine interferon (IFN) gamma plays a role in the injury of SH-SY5Y cells caused by MPP(+) (1-methyl-4-phenylpyridinium). First of all, IFN-gamma sensitized cells to the neurotoxin MPP(+), as determined by MTT (3-(4,5-dimethylthiazol-2-y1)-2,5-diphenyltetrazolium bromide) assay. MPP(+)-injured cells showed higher reactive oxygen species (ROS) levels, which was reinforced by IFN-gamma. The injury triggered a marked expression of the neuronal NOS (nNOS) enzyme. L-NAME [N(ω)-nitro-L-arginine methyl ester, a non-specific NOS inhibitor] reestablished the cell viability after IFN-gamma challenging, and recovered cells from MPP(+) injury (95.0 vs. 84.7 %; P < 0.05). Seven-NI (7-nitroindazole, a nNOS inhibitor) protected cells against the injury by MPP(+) co-administered with IFN-gamma. Both inhibitors restrained the apoptosis of SH-SY5Y cells caused by MPP(+)/IFN-gamma. Regarding oxidative stress, L-NAME and 7-NI attenuated the increase in ROS levels caused by MPP(+) (45.3 or 48.4 vs. 87.9 %, P < 0.05). Indeed, L-NAME was more effective than 7-NI for reducing oxidative stress caused by MPP(+) under IFN-gamma exposition. The nNOS gene silencing by small-interfering RNAs recovered cells challenged by IFN-gamma (24 h), or MPP(+) (8 h). In conclusion, IFN-gamma sensitizes cells to MPP(+)-induced injury, also causing an increase in ROS levels. Pretreating cells with L-NAME or 7-NI reverts both the oxidative stress and apoptosis triggered by the neurotoxin MPP(+). Taking together, our data reinforce that IFN-gamma and NOS enzymes play a role in oxidative stress and dopaminergic cell death triggered by MPP(+).
ResumoEste artigo discute o direito ao conhecimento da origem biológica da pessoa gerada por técnica de reprodução humana assistida, apresentando argumentos e problemas envolvidos nesse complexo processo que inclui diferentes interesses. Nesse sentido, foi desenvolvido um estudo hipotético-dedutivo, com base referencial teórica sustentada na bioética e no direito, na medida em que esses dois campos se interseccionavam quanto à natureza da matéria. O estudo avança, ainda, abordando os riscos decorrentes dos avanços tecnológicos e das expectativas dos sujeitos envolvidos, inclusive a vulnerabilidade, o consentimento para doação de gametas e o anonimato dos doadores. Discute, também, os conceitos de "identidade genética" e direito ao conhecimento da "origem biológica", traçando analogia com a legislação brasileira relativa à adoção. Por fim, trata do chamado "pertencimento do segredo", refletindo sobre os argumentos encontrados na literatura afim, inclusive o contexto de "desbiologização" atualmente defendido pelos tribunais superiores. Palavras-chave: Bioética. Direito à saúde. Técnicas reprodutivas. Privacidade. ResumenDerecho al conocimiento del origen biológico en reproducción humana asistida: reflexiones bioéticas y legales Este artículo aborda el derecho al conocimiento del origen biológico de la persona generada por técnica de reproducción humana asistida, presentando los argumentos y problemas implicados en este complejo proceso que involucra diferentes intereses. En este sentido, se ha desarrollado un estudio hipotético-deductivo, con sustento teórico en bioética y derecho, y la intersección de estos dos campos respecto a la naturaleza del tema. El estudio avanza, haciendo relación a los riesgos de los avances tecnológicos y las expectativas de los participantes, la vulnerabilidad, el consentimiento para la donación de gametos y el anonimato de los donantes. Son analizados también los conceptos de "identidad genética" y el derecho a conocer el "origen biológico", haciendo una analogía con la legislación brasileña relativa a la adopción. Por último, se aborda la llamada "pertenencia del secreto ", al reflexionar sobre los argumentos de la literatura al respecto, incluyendo el contexto de " desbiologización " actualmente defendida por los tribunales superiores. Palabras-clave: Bioética. Derecho a la salud. Técnicas reproductivas. Privacidad. Abstract Right to knowledge of biological origin in Human Assisted Reproduction: bioethical and legal reflectionsThis article discusses the right to know the biological origins of a person generated by the Heterologous Human Reproduction technique, presenting arguments and issues related to this complex process, which involves different interests. In this sense, a hypothetical-deductive study is developed based on intersections of nature and content between Bioethics and Law. The study progresses by approaching the risks brought by technological advances and the expectations of all subjects involved, as well as vulnerabilities, the need for consent for gamete donation an...
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