Fucoxanthin Mitigates Subarachnoid Hemorrhage-Induced Oxidative Damage via Sirtuin 1-Dependent Pathway

Autor: Da-Yong Xia, Yue Lu, Chun-Hua Hang, Xiang-Sheng Zhang, Han Wang, Tao Tao, Xun-Zhi Liu, Guang-Jie Liu, Cang Liu, Wei Li
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Antioxidant
Cell Survival
medicine.medical_treatment
Carbazoles
Neuroscience (miscellaneous)
Apoptosis
Brain Edema
Oxidative phosphorylation
Xanthophylls
Pharmacology
medicine.disease_cause
Neuroprotection
Antioxidants
Rats
Sprague-Dawley
Lipid peroxidation
03 medical and health sciences
Cellular and Molecular Neuroscience
chemistry.chemical_compound
0302 clinical medicine
Sirtuin 1
medicine
Animals
cardiovascular diseases
Cells
Cultured
Neurons
chemistry.chemical_classification
Reactive oxygen species
biology
Brain
Subarachnoid Hemorrhage
Mitochondria
nervous system diseases
Mice
Inbred C57BL
Oxidative Stress
030104 developmental biology
Neurology
chemistry
Nerve Degeneration
biology.protein
Female
Reactive Oxygen Species
030217 neurology & neurosurgery
Oxidative stress
Signal Transduction
Zdroj: Molecular Neurobiology. 57:5286-5298
ISSN: 1559-1182
0893-7648
Popis: 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.
Databáze: OpenAIRE
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