(1)
Cadmium is an extremely toxic
metal commonly found in industrial workplaces, a food contaminant and a major component of cigarette
smoke.
Cadmium can severely damage several organs, including the brain. In this work, we have studied both the
cadmium toxicity on rat cortical neurons in culture and the possible protective effect of serum. (2) Our results indicate that: (1)
cadmium is taken up by the neurons in a dose and serum dependent way; (2)
cadmium, at concentrations from 1 micro M or 10 micro M (depending on the absence or the presence of serum) up to 100 micro M, decreases the metabolic capacity, which was evaluated by the
XTT (tetrazolium salt) test; (3)
cadmium induces apoptosis and LDH (
lactate dehydrogenase) release in a dose dependent way; (4) in a serum-free medium, the
cadmium-induced apoptosis is accompanied by
caspase-3 activation; (5) both the
caspase-3 activation and the
cadmium-induced apoptosis are reversed by N-acethyl-
Asp-Glu-Val-Asp-
aldehyde (
Ac-DEVD-CHO), a selective
caspase-3 inhibitor, indicating that the
caspase-3 pathway is involved in
cadmium-induced apoptosis in cortical neurons; and (6) the
cadmium concentrations which produce
caspase-3 activation do not modify the intracellular
ATP levels; however, higher
cadmium concentrations lead to both intracellular
ATP depletion and
ATP release, but do not increase the
caspase-3 activity, indicating that
cadmium also produces cellular death by
necrosis. (3) These results suggest that
cadmium induces either apoptosis or
necrosis in rat cortical neurons, depending on the
cadmium concentration.