Antioxidant effects of N-acetylserotonin: possible mechanisms and clinical implications.
This paper will review our recent data relevant to the antioxidant effects of N-acetylserotonin (NAS), the immediate precursor of melatonin, the pineal gland indole. Mechanisms of the antioxidant effects of NAS might involve interaction with melatonin type 3 receptors and nonreceptor mechanisms such as stimulation of glutathione peroxidase, an antioxidant enzyme; inhibition of lipid peroxidation; suppression of phospholipase A2 activation; attenuation of tumor necrosis factor-alpha production; prevention of pathological opening of the mitochondrial permeability transition pores; and inhibition of sepiapterin reductase, the key enzyme of biosynthesis of tetrahydrobiopterin, the essential cofactor of nitric oxide synthase. NAS actions on some of these enzymes might be receptor-mediated. Protective effects of NAS against oxidative damage are independent from the effect of melatonin and, depending on the model, are 5 to 20 times stronger than that of melatonin. Antioxidant effect of NAS might underpin its cognition-enhancing, antiaging, antidepressant, antihypertensive, and antitumor effects. NAS and its derivatives might be useful in protection against oxidative stress-related disorders (cell death, mutagenesis, aging) and diseases (sepsis, cancer, postischemic trauma, Alzheimer's disease, parkinsonism).
Oxenkrug
Gregory
G
Melatonin Clinic and Pineal Research Laboratory, Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts 02135, USA. goxenkrug@tufts-nemc.org
D000375:Aging / Q000187:drug effects; D000818:Animals; D000928:Antidepressive Agents; D000975:Antioxidants; D001794:Blood Pressure / Q000187:drug effects; D003071:Cognition / Q000187:drug effects; D019417:Hindlimb Suspension; D015227:Lipid Peroxidation / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D011918:Rats, Inbred SHR; D017382:Reactive Oxygen Species / Q000378:metabolism; D016028:Receptors, Leukocyte-Adhesion / Q000187:drug effects; D044094:Receptors, Melatonin / Q000187:drug effects; D012701:Serotonin / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D012772:Shock, Septic / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000928:Antidepressive Agents; D000975:Antioxidants; D017382:Reactive Oxygen Species; D016028:Receptors, Leukocyte-Adhesion; D044094:Receptors, Melatonin; D014409:Tumor Necrosis Factor-alpha; D012701:Serotonin; D010741:Phospholipases A; D054467:Phospholipases A2; C006389:N-acetylserotonin