التفاصيل البيبلوغرافية
| العنوان: |
Neuronal Glutathione Content and Antioxidant Capacity can be Normalized In Situ by N-acetyl Cysteine Concentrations Attained in Human Cerebrospinal Fluid |
| المؤلفون: |
Reyes, Reno C, Cittolin-Santos, Giordano Fabricio, Kim, Ji-Eun, Won, Seok Joon, Brennan-Minnella, Angela M, Katz, Maya, Glass, Graham A, Swanson, Raymond A |
| المصدر: |
Neurotherapeutics, vol 13, iss 1 |
| بيانات النشر: |
eScholarship, University of California |
| سنة النشر: |
2016 |
| المجموعة: |
University of California: eScholarship |
| مصطلحات موضوعية: |
Biological Psychology, Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Psychology, Complementary and Integrative Health, Neurosciences, Brain Disorders, Mental Health, 5.1 Pharmaceuticals, Development of treatments and therapeutic interventions, Neurological, Acetylcysteine, Animals, Antioxidants, Brain Chemistry, Dose-Response Relationship, Drug, Glutathione, Humans, Mice, Inbred C57BL, Rats, Sprague-Dawley, Cysteine, Parkinson's disease, oxidative stress, human, cerebrospinal fluid, target engagement, Parkinson’s disease |
| جغرافية الموضوع: |
217 - 225 |
| الوصف: |
N-acetyl cysteine (NAC) supports the synthesis of glutathione (GSH), an essential substrate for fast, enzymatically catalyzed oxidant scavenging and protein repair processes. NAC is entering clinical trials for adrenoleukodystrophy, Parkinson's disease, schizophrenia, and other disorders in which oxidative stress may contribute to disease progression. However, these trials are hampered by uncertainty about the dose of NAC required to achieve biological effects in human brain. Here we describe an approach to this issue in which mice are used to establish the levels of NAC in cerebrospinal fluid (CSF) required to affect brain neurons. NAC dosing in humans can then be calibrated to achieve these NAC levels in human CSF. The mice were treated with NAC over a range of doses, followed by assessments of neuronal GSH levels and neuronal antioxidant capacity in ex vivo brain slices. Neuronal GSH levels and antioxidant capacity were augmented at NAC doses that produced peak CSF NAC concentrations of ≥50 nM. Oral NAC administration to humans produced CSF concentrations of up to 10 μM, thus demonstrating that oral NAC administration can surpass the levels required for biological activity in brain. Variations of this approach may similarly facilitate and rationalize drug dosing for other agents targeting central nervous system disorders. |
| نوع الوثيقة: |
article in journal/newspaper |
| وصف الملف: |
application/pdf |
| اللغة: |
unknown |
| العلاقة: |
qt2rd8g0fn; https://escholarship.org/uc/item/2rd8g0fnTest |
| الإتاحة: |
https://escholarship.org/uc/item/2rd8g0fnTest |
| حقوق: |
public |
| رقم الانضمام: |
edsbas.87EAE7BE |
| قاعدة البيانات: |
BASE |
