Mercury (Hg) and
cadmium (Cd) are the major toxic
heavy metals and are known to induce neurotoxicity. Although many studies have shown that several
heavy metals have neurotoxic effects, the cellular and molecular mechanisms thereof are still not clear. Oxidative stress is reported to be a common and important mechanism in cytotoxicity induced by
heavy metals. However, the assays for identifying toxic mechanisms were not performed under the same experimental conditions, making it difficult to compare toxic properties of the
heavy metals. In this study, we investigated the mechanisms underlying neurotoxicity induced by
heavy metals and H2O2, focusing on cell death, cell proliferation, and oxidative stress under the same experimental condition. Our results showed that MeHg caused
lactate dehydrogenase (LDH) release,
caspase activation and cell-cycle alteration, and ROS generation in accordance with decreased cell viability.
HgCl2 caused LDH release and cell-cycle alteration, but not
caspase activation.
CdCl2 had a remarkable effect on the cell cycle profiles without induction of LDH release,
caspase activation, or ROS generation. Pretreatment with
N-acetyl-l-cysteine (NAC) prevented the decrease in cell viability induced by MeHg and
HgCl2, but not
CdCl2. Our results demonstrate a clear difference in neurotoxic mechanisms induced by MeHg,
HgCl2,
CdCl2 or H2O2 in SH-SY5Y cells. Elucidating the characteristics and mechanisms of each
heavy metal under the same experimental conditions will be helpful to understand the effect of
heavy metals on health and to develop a more effective
therapy for
heavy metal poisoning.