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Melatonin protects SK-N-SH neuroblastoma cells from amphetamine-induced neurotoxicity. 2007

Sirirat Klongpanichapak, and Pansiri Phansuwan-Pujito, and Manuchair Ebadi, and Piyarat Govitrapong
Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakornpathom, Thailand.

Several hypotheses regarding the mechanism underlying amphetamine-induced neurotoxicity have been proposed. One of them is based on the observation of free radical formation and oxidative stress produced by auto-oxidation of dopamine (DA). The formation of DA-related reactive oxygen species (ROS) such as superoxide and hydroxyl radicals appears to play an important role in amphetamine-induced neurotoxicity. Melatonin, the main secretory product of pineal gland, is well known for its protective effects that are currently attributed mainly to its radical scavenging and antioxidant properties. The present study was conducted to investigate the protective effects of melatonin on d-amphetamine (AMPH)-induced neurotoxicity in cultured human dopaminergic neuroblastoma SK-N-SH cells. Our data indicate that AMPH significantly reduces cell viability, induces oxidative stress (enhances ROS production and malondialdehyde levels), up-regulates alpha-synuclein expression and decreases intracellular ATP levels. However, pretreatment of SK-N-SH cells with melatonin prevents AMPH-induced loss of cell viability and induction of oxidative stress, while reducing alpha-synuclein expression and increasing ATP production. These results suggest that the antioxidant properties of melatonin may provide a protective mechanism against AMPH-induced neuronal degeneration.

UI MeSH Term Description Entries
D008550 Melatonin A biogenic amine that is found in animals and plants. In mammals, melatonin is produced by the PINEAL GLAND. Its secretion increases in darkness and decreases during exposure to light. Melatonin is implicated in the regulation of SLEEP, mood, and REPRODUCTION. Melatonin is also an effective antioxidant.
D009447 Neuroblastoma A common neoplasm of early childhood arising from neural crest cells in the sympathetic nervous system, and characterized by diverse clinical behavior, ranging from spontaneous remission to rapid metastatic progression and death. This tumor is the most common intraabdominal malignancy of childhood, but it may also arise from thorax, neck, or rarely occur in the central nervous system. Histologic features include uniform round cells with hyperchromatic nuclei arranged in nests and separated by fibrovascular septa. Neuroblastomas may be associated with the opsoclonus-myoclonus syndrome. (From DeVita et al., Cancer: Principles and Practice of Oncology, 5th ed, pp2099-2101; Curr Opin Oncol 1998 Jan;10(1):43-51) Neuroblastomas
D009474 Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM. Nerve Cells,Cell, Nerve,Cells, Nerve,Nerve Cell,Neuron
D003913 Dextroamphetamine The d-form of AMPHETAMINE. It is a central nervous system stimulant and a sympathomimetic. It has also been used in the treatment of narcolepsy and of attention deficit disorders and hyperactivity in children. Dextroamphetamine has multiple mechanisms of action including blocking uptake of adrenergics and dopamine, stimulating release of monamines, and inhibiting monoamine oxidase. It is also a drug of abuse and a psychotomimetic. d-Amphetamine,Curban,Dexamfetamine,Dexamphetamine,Dexedrine,Dextro-Amphetamine Sulfate,DextroStat,Dextroamphetamine Sulfate,Oxydess,d-Amphetamine Sulfate,dextro-Amphetamine,Dextro Amphetamine Sulfate,Sulfate, Dextroamphetamine,d Amphetamine,d Amphetamine Sulfate,dextro Amphetamine
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D045744 Cell Line, Tumor A cell line derived from cultured tumor cells. Tumor Cell Line,Cell Lines, Tumor,Line, Tumor Cell,Lines, Tumor Cell,Tumor Cell Lines

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