Melatonin protects SK-N-SH neuroblastoma cells from amphetamine-induced neurotoxicity.
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.
Klongpanichapak
Sirirat
S
Neuro-Behavioural Biology Center, Institute of Science and Technology for Research and Development, Mahidol University, Salaya, Nakornpathom, Thailand.
Phansuwan-Pujito
Pansiri
P
Ebadi
Manuchair
M
Govitrapong
Piyarat
P
D045744:Cell Line, Tumor; D003913:Dextroamphetamine / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D006801:Humans; D008550:Melatonin / Q000502:physiology*; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology* / Q000502:physiology
D008550:Melatonin; D003913:Dextroamphetamine