Comparative analysis of <i>in vitro</i> neurotoxicity of methylmercury, mercury, cadmium, and hydrogen peroxide on SH-SY5Y cells

Abstract

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 H 2 O 2 , 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. HgCl 2 caused LDH release and cell-cycle alteration, but not caspase activation. CdCl 2 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 HgCl 2 , but not CdCl 2 . Our results demonstrate a clear difference in neurotoxic mechanisms induced by MeHg, HgCl 2 , CdCl 2 or H 2 O 2 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.

DHA and Its Metabolites Have a Protective Role against Methylmercury-Induced Neurotoxicity in Mouse Primary Neuron and SH-SY5Y Cells

“…We first conducted an MTT assay to determine the dose–response of the cytotoxicity of MeHg in human neuroblastoma SH-SY5Y cells, applying the MeHg concentrations of 1–10 µM for 24 h. The viability of the cells treated with 3 µM MeHg was reduced to approximately 40% compared to the non-treated cells, and 10 µM MeHg significantly reduced the cell viability ( Figure 1 A). These results are consistent with previous findings in SH-SY5Y cells [ 14 , 15 ]. We next investigated the time–response of the cell viability by treatment with 3 µM MeHg for 0–24 h. The exposure of the cells with MeHg for up to 2 h did not affect the cell viability, and after 2 h the cell viability declined in a time-dependent manner ( Figure 1 B).…”

Toxicity of mercury on the brain: ability of extract of Pistacia atlantica regulated effect

“…The present results corroborate the previous results which demonstrated that exposure to mercury stimulated the generation of ROS. Our results agree with further studies 22,23 . the combination of Hg and the P. atlantica extract in our study showed a reduction in TBARS levels in the brain.…”

In Vitro Hepatotoxic and Neurotoxic Effects of Titanium and Cerium Dioxide Nanoparticles, Arsenic and Mercury Co-Exposure

“…The results here presented show a different cytotoxic response of HepG2 and SH-SY5Y that has equally been observed by other authors for TiO 2 NPs [ 47 ], CeO 2 NPs [ 48 ], As and Hg [ 49 ], with the neural cell line being more sensitive than HepG2 in all cases, after 24 h exposure. The same authors also observed a dose-dependent cytotoxic effect as observed in this study.…”