RESUMEN
Oxidative stress is a key component of the pathological cascade in subarachnoid hemorrhage (SAH). Fucoxanthin (Fx) possesses a strong antioxidant property and has shown neuroprotective effects in acute brain injuries such as ischemic stroke and traumatic brain injury. Here, we investigated the beneficial effects of Fx against SAH-induced oxidative insults and the possible molecular mechanisms. Our data showed that Fx could significantly inhibit SAH-induced reactive oxygen species production and lipid peroxidation, and restore the impairment of endogenous antioxidant enzymes activities. In addition, Fx supplementation improved mitochondrial morphology, ameliorated neural apoptosis, and reduced brain edema after SAH. Moreover, Fx administration exerted an improvement in short-term and long-term neurobehavior functions after SAH. Mechanistically, Fx inhibited oxidative damage and brain injury after SAH by deacetylation of forkhead transcription factors of the O class and p53 via sirtuin 1 (Sirt1) activation. EX527, a selective Sirt1 inhibitor, significantly abated Fx-induced Sirt1 activation and abrogated the antioxidant and neuroprotective effects of Fx after SAH. In primary neurons, Fx similarly suppressed oxidative insults and improved cell viability. These effects were associated with Sirt1 activation and were reversed by EX527 treatment. Taken together, our study explored that Fx provided protection against SAH-induced oxidative insults by inducing Sirt1 signaling, indicating that Fx might serve as a potential therapeutic drug for SAH.
Asunto(s)
Estrés Oxidativo/efectos de los fármacos , Transducción de Señal , Sirtuina 1/metabolismo , Hemorragia Subaracnoidea/complicaciones , Xantófilas/farmacología , Animales , Antioxidantes/farmacología , Apoptosis/efectos de los fármacos , Encéfalo/patología , Edema Encefálico/complicaciones , Edema Encefálico/patología , Carbazoles/farmacología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Masculino , Ratones Endogámicos C57BL , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Degeneración Nerviosa/complicaciones , Degeneración Nerviosa/patología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Effect of ginsenoside total saponin (GTS) on the regulation of P450 of livers of rats after γ-ray irradiation was studied. Rats were irradiated by the 6°Coγ-ray for one-time dose of 5.5 Gy, dose rate of 117.1-119.2 cGy. The cocktail probe, qPCR and Western blot were used to detect expression of enzymatic activites, mRNA and protein of rats. Contrasted with blank group, expression of CYP1A2, 2B1, 2E1, 3A4 of irradiation group showed a up-regulated (P < 0.05). Contrasted with irradiation group, exprression of CYP1A2, 2B1, 2E1, 3A4 of GTS group showed a downward trend. GTS had negative agonistic action against expression of P450 of rats by irradiatied.