In vitro cyto-toxic assessment of heavy metals and their binary mixtures on mast cell-like, rat basophilic leukemia (RBL-2H3) cells

Eze, Chukwuebuka ThankGod; Michelangeli, Francesco; Otitoloju, Adebayo A.

doi:10.1016/j.chemosphere.2019.02.035

Cited by 14 publications

(4 citation statements)

References 51 publications

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“…Further, mRNA expressions of RIPK3, MLKL, IL‐1β and TNF‐α were up‐regulated while RIPK1 was down‐regulated, which was reversed by the RIPK3 inhibitor GSK872. A previous study has been made for Cd, Pb, As (arsenic) and Cr (chromium) showing that Cd poses larger individual cytotoxicity and results in necroptosis, while binary mixtures for some metals present less cytotoxicity than their individual actions, which indicates an antagonistic effect of co‐exposure and may be associated with metal ion properties and their modes of action 45 . Co‐exposure of BDE‐209 and Pb has a synergistic effect on obstruction of neurodevelopment of zebrafish larvae 46 .…”

Section: Discussionmentioning

confidence: 99%

Cadmium (Cd) and 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) co‐exposure induces acute kidney injury through oxidative stress and RIPK3‐dependent necroptosis

Tang

Zhang

Chen

et al. 2023

Environmental Toxicology

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Environmental pollution is complex, and co‐exposure can accurately reflect the true environmental conditions that are important for assessment of human health. Cadmium (Cd) is a widespread toxicant that can cause acute kidney injury (AKI), while its combined effect with 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) is not fully understood. Thus, we used an in vivo model where C57BL/6J mice were treated with low dietary intake of Cd (5 mg/kg/day) and/or BDE‐47 (1 mg/kg/day) for 28 days to examine AKI, and in vitro experiments to investigate the possible mechanism. Results showed that Cd or BDE‐47 caused pathological kidney damage, accompanied by elevated urea nitrogen (BUN) and urinary creatinine, as well as increased interleukin‐1β (IL‐1β) and tumor necrosis factor‐α (TNF‐α), and reduced IL‐10 in kidney tissues. In vitro Cd or BDE‐47 exposure decreased cell viability and induced cell swelling and blebbing of human embryonic kidney 293 (HEK‐293) and renal tubular epithelial cell lines (HKCs), and changes in co‐exposure was larger than that in Cd and BDE‐47 treatment. Oxidative stress indicators of the reactive oxygen species (ROS) and malondialdehyde (MDA) were elevated, while the antioxidant superoxide dismutase (SOD) was decreased. Necrosis occurred with increased lactate dehydrogenase (LDH) release and propidium iodide (PI) staining, which was attenuated by the ROS scavenger N‐acetyl‐L‐cysteine (NAC). Furthermore, necroptotic genes of receptor‐interacting protein kinase‐3 (RIPK3), classical mixed lineage kinase domain‐like protein‐dependent (MLKL), IL‐1β and TNF‐α were up‐regulated, whereas RIPK1 was down‐regulated, which was attenuated by the RIPK3 inhibitor GSK872. These findings demonstrate that Cd or BDE‐47 alone produces kidney toxicities, and co‐exposure poses an additive effect, resulting in AKI via inducing oxidative stress and regulating RIPK3‐dependent necroptosis, which offers a further mechanistic understanding for kidney damage, and the combined effect of environmental pollutants should be noticed.

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Section: Discussionmentioning

confidence: 99%

Cadmium (Cd) and 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) co‐exposure induces acute kidney injury through oxidative stress and RIPK3‐dependent necroptosis

Tang

Zhang

Chen

et al. 2023

Environmental Toxicology

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“…The metal in the composition of PM 2.5 only accounts for 2–8%; however, due to the long half-life, it may be hard to be excreted when it enters the human body, and then it will be accumulated in the human body [ 7 , 8 , 9 ]. Heavy metals could enhance the oxidative stress response of lung epithelial cells, produce enzyme activity, affect the cell cycle, trigger cell apoptosis, and cause lung function injuries [ 10 , 11 , 12 , 13 ]. Cell exposure experiments prove that exposure to low concentrations of heavy metals can also affect normal cellular immune responses [ 14 ].…”

Section: Introductionmentioning

confidence: 99%

“…Mixed metals are more toxic to cells than single ones. The apoptosis rate of A549 cells after exposure to mixed metals could reach 36.5% [ 13 , 14 , 15 , 16 ]. The results of toxicity experiments on lung cancer cell lines and rats show that heavy metals in particles can inhibit the expression of proteins related to redox homeostasis in cells, and overexpresses the proteins that are related to DNA damage [ 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

Inhalation Bioaccessibility and Risk Assessment of Metals in PM2.5 Based on a Multiple-Path Particle Dosimetry Model in the Smelting District of Northeast China

Sun

Zheng

Wang

et al. 2022

IJERPH

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PM2.5 can deposit and partially dissolve in the pulmonary region. In order to be consistent with the reality of the pulmonary region and avoid overestimating the inhalation human health risk, the bioaccessibility of PM2.5 heavy metals and the deposition fraction (DF) urgently needs to be considered. This paper simulates the bioaccessibility of PM2.5 heavy metals in acidic intracellular and neutral extracellular deposition environments by simulating lung fluid. The multipath particle dosimetry model was used to simulate DF of PM2.5. According to the exposure assessment method of the U.S. Environmental Protection Agency, the inhalation exposure dose threshold was calculated, and the human health risk with different inhalation exposure doses was compared. The bioaccessibility of heavy metals is 12.1–36.2%. The total DF of PM2.5 in adults was higher than that in children, and children were higher than adults in the pulmonary region, and gradually decreased with age. The inhalation exposure dose threshold is 0.04–14.2 mg·kg−1·day−1 for the non-carcinogenic exposure dose and 0.007–0.043 mg·kg−1·day−1 for the carcinogenic exposure dose. Cd and Pb in PM2.5 in the study area have a non-carcinogenic risk to human health (hazard index < 1), and Cd has no or a potential carcinogenic risk to human health. A revised inhalation health risk assessment may avoid overestimation.

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“…Heavy metals may bioaccumulate, and animal models indicate that the concentrations of heavy metals and the extent of their effects are nonlinear [34]. Moreover, the cellular toxicity of multiple heavy metals is not merely the sum of the toxicity of single heavy metals, and combinations of different heavy metals can produce synergistic or antagonistic effects [35,36]. Therefore, the health risks of different heavy metals to a population should not be simply determined by the addition of effects.…”

Section: Introductionmentioning

confidence: 99%

Source Analysis and Human Health Risk Assessment Based on Entropy Weight Method Modification of PM2.5 Heavy Metal in an Industrial Area in the Northeast of China

et al. 2021

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In this study, PM2.5 was analyzed for heavy metals at two sites in industrial northeast China to determine their sources and human health risks during heating and non-heating periods. A positive matrix factorization (PMF) model determined sources, and US Environmental Protection Agency (USEPA) and entropy weight methods were used to assess human health risk. PM2.5 heavy metal concentrations were higher in the heating period than in the non-heating period. In the heating period, coal combustion (59.64%) was the primary heavy metal source at Huagong Hospitals, and the contribution rates of industrial emissions and traffic emissions were 21.06% and 19.30%, respectively. Industrial emissions (42.14%) were the primary source at Xinqu Park, and the contribution rates of coal combustion and traffic emissions were 34.03% and 23.83%, respectively. During the non-heating period, coal combustion (45.29%) and industrial emissions 45.29% and 44.59%, respectively, were the primary sources at Huagong Hospital, and the traffic emissions were 10.12%. Industrial emissions (43.64%) were the primary sources at Xinqu Park, where the coal combustion and traffic emissions were 25.35% and 31.00%, respectively. In the heating period, PM2.5 heavy metals at Xinqu Park had noncarcinogenic and carcinogenic risks, and the hazard index of children (5.74) was higher than that of adult males (5.28) and females (4.49). However, adult males and females had the highest lifetime carcinogenic risk (1.38 × 10−3 and 1.17 × 10−3) than children (3.00 × 10−4). The traditional USEPA and entropy weight methods both produced reasonable results. However, when there is a difference between the two methods, the entropy weight method is recommended to assess noncarcinogenic health risks.

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In vitro cyto-toxic assessment of heavy metals and their binary mixtures on mast cell-like, rat basophilic leukemia (RBL-2H3) cells

Cited by 14 publications

References 51 publications

Cadmium (Cd) and 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) co‐exposure induces acute kidney injury through oxidative stress and RIPK3‐dependent necroptosis

Cadmium (Cd) and 2,2′,4,4′‐tetrabromodiphenyl ether (BDE‐47) co‐exposure induces acute kidney injury through oxidative stress and RIPK3‐dependent necroptosis

Inhalation Bioaccessibility and Risk Assessment of Metals in PM2.5 Based on a Multiple-Path Particle Dosimetry Model in the Smelting District of Northeast China

Source Analysis and Human Health Risk Assessment Based on Entropy Weight Method Modification of PM2.5 Heavy Metal in an Industrial Area in the Northeast of China

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