Reduced oxidative damage in ALS by high-dose enteral melatonin treatment
| Autor: | Burkhard Poeggeler, Klaus-Armin Nave, Jeannine Dietrich, Gerald Hüther, Bach Alfred, Hannelore Ehrenreich, Claudia Bartels, Anna-Leena Sirén, Gundula Rohde, Armin Schneider, Nina Mertens, Matthias Bohn, Mathias Bähr, Esther Polking, Rüdiger Hardeland, Swetlana Sperling, Jochen H. Weishaupt |
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| Rok vydání: | 2006 |
| Předmět: |
Male
Pathology Antioxidant medicine.medical_treatment Pharmacology medicine.disease_cause Mice Superoxide Dismutase-1 0302 clinical medicine Endocrinology Vitamin E Amyotrophic lateral sclerosis Melatonin Neurons 0303 health sciences biology Middle Aged Cytoprotection 3. Good health Survival Rate Female medicine.drug Adult medicine.medical_specialty SOD1 Glutamic Acid Mice Transgenic Neuroprotection Cell Line Superoxide dismutase 03 medical and health sciences medicine Animals Humans Aged 030304 developmental biology Dose-Response Relationship Drug Superoxide Dismutase business.industry Amyotrophic Lateral Sclerosis medicine.disease Oxidative Stress biology.protein Reactive Oxygen Species business Biomarkers 030217 neurology & neurosurgery Oxidative stress Follow-Up Studies |
| Zdroj: | Journal of Pineal Research. 41:313-323 |
| ISSN: | 1600-079X 0742-3098 |
| DOI: | 10.1111/j.1600-079x.2006.00377.x |
| Popis: | Amyotrophic lateral sclerosis (ALS) is the collective term for a fatal motoneuron disease of different etiologies, with oxidative stress as a common molecular denominator of disease progression. Melatonin is an amphiphilic molecule with a unique spectrum of antioxidative effects not conveyed by classical antioxidants. In preparation of a possible future clinical trial, we explored the potential of melatonin as neuroprotective compound and antioxidant in: (1) cultured motoneuronal cells (NSC-34), (2) a genetic mouse model of ALS (SOD1(G93A)-transgenic mice), and (3) a group of 31 patients with sporadic ALS. We found that melatonin attenuates glutamate-induced cell death of cultured motoneurons. In SOD1(G93A)-transgenic mice, high-dose oral melatonin delayed disease progression and extended survival. In a clinical safety study, chronic high-dose (300 mg/day) rectal melatonin was well tolerated during an observation period of up to 2 yr. Importantly, circulating serum protein carbonyls, which provide a surrogate marker for oxidative stress, were elevated in ALS patients, but were normalized to control values by melatonin treatment. This combination of preclinical effectiveness and proven safety in humans suggests that high-dose melatonin is suitable for clinical trials aimed at neuroprotection through antioxidation in ALS. |
| Databáze: | OpenAIRE |
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