Comparative In Vitro Toxicity Evaluation of Heavy Metals (Lead, Cadmium, Arsenic, and Methylmercury) on HT-22 Hippocampal Cell Line

Abstract

Heavy metals are considered some of the most toxic environmental pollutants. Exposure to heavy metals including lead (Pb), cadmium (Cd), arsenic (As), and methyl mercury (MeHg) has long been known to cause damage to human health. Many recent studies have supported the hippocampus as the major target for these four metals for inflicting cognitive dysfunction. In the present study, we proposed hippocampal relevant in vitro toxicity of Pb, Cd, As, and MeHg in HT-22 cell line. This study reports, initially, cytotoxic effects in acute, subchronic, chronic exposures. We further investigated the mechanistic potency of DNA damage and apoptosis damage with the observed cytotoxicity. The genotoxicity and apoptosis were measured by using the comet assay, annexin-V FTIC / propidium iodide (PI) assay, respectively. The results of cytotoxicity assay clearly demonstrated significant concentration and time-dependent effects on HT-22 cell line. The genotoxic and apoptosis effects also concentration-dependent fashion with respect to their potency in the range of IC-IC maximal level of damage observed in MeHg. In conclusion, the obtained result suggests concentration and potency-dependent response; the maximal level of toxicity was observed in MeHg. These novel findings support that Pb, Cd, As, and MeHg induce cytotoxic, genotoxic, and apoptotic effects on HT-22 cells in potency-dependent manner; MeHg> As> Cd> Pb. Therefore, the toxicity of Pb, Cd, As, and MeHg could be useful for knowing the common underlying molecular mechanism, and also for estimating the mixture impacts on HT-22 cell line.

Differential protein expression of hippocampal cells associated with heavy metals (Pb, As, and MeHg) neurotoxicity: Deepening into the molecular mechanism of neurodegenerative diseases

“…The obtained 8 days exposure MTT results were useful for further mechanistic based assays such as apoptosis to know the chronic risk of heavy metals on HT-22 cells. For that purpose, in a previous study, cells were treated with a range of IC 10 to IC 30 concentrations (µM), and results were reported in Karri et al [65]. This report confirmed that Pb induced apoptosis process was low in HT-22 cells and agreement with reported studies in (Figure 1) [80].…”

“…As expected, all three metals showed concentration and time-dependent cytotoxic effect. Results and discussion for Pb, As and MeHg cytotoxicity experiments at chronic conditions were reported by Karri et al [65]. Upon the Pb exposure (10-100µM)) cell death was significantly lower indicating that sensitivity of hippocampal cells towards Pb is relatively low.…”

Cadmium (Cd) chloride affects the nutrient uptake and Cd-resistant bacterium reduces the adsorption of Cd in muskmelon plants

“…In this study, we explored the effect of Cd and Cdresistant bacterium "N3" on N, P, and K uptake in grafted and nongrafted plants under the two concentrations of Cd. Cd is one of the hazardous heavy metals that restrains plant regeneration and growth [24][25][26][27]. The shoot dry weight and total dry weights of the nongrafted muskmelon plants decreased under 50 and 100 µM Cd treatments (Figure 2a).…”

An in vitro cytotoxic approach to assess the toxicity of heavy metals and their binary mixtures on hippocampal HT-22 cell line

“…This difference could be due to the different uptake mechanisms of heavy metals by the HT-22 cells this difference among the cytotoxicity results of heavy metals suggests that some underlying unique intracellular mechanism is responsible for the hippocampus damage. • The summary of cell viability data of heavy metals for different exposure times (1 day, 3 days, 8 days) are presented in the supplementary material (Annex-I) and detail study can be found in Karri et al 2017. Figure 2.…”