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.