Reactive oxygen species production and inflammatory effects of ambient PM2.5 -associated metals on human lung epithelial A549 cells "one year-long study": The Delhi chapter.

Nickel (Ni) is a widely distributed metal in the environment and an important pollutant due to its widespread industrial applications. Ni has various toxicity in humans and experimental animals, including carcinogenicity. However, the carcinogenic effects of Ni remain troublesome. Cell cycle dysregulation may be an important carcinogenic mechanism and is also a potential molecular mechanism for Ni complexes anti-cancerous effects. Therefore, we conducted a literature review to summarize the effects of Ni on cell cycle. Up to now, there were three different reports on Ni-induced cell cycle arrest: (i) Ni can induce cell cycle arrest in G0/G1 phase, phosphorylation and degradation of IkappaB kinase-alpha (IKKα)–dependent cyclin D1 and phosphoinositide-3-kinase (PI3K)/serine-threonine kinase (Akt) pathway–mediated down-regulation of expressions of cyclin-dependent kinases 4 (CDK4) play important role in it; (ii) Ni can induce cell cycle arrest in S phase, but the molecular mechanism is not known; (iii) G2/M phase is the target of Ni toxicity, and Ni compounds cause G2/M cell cycle phase arrest by reducing cyclinB1/Cdc2 interaction through the activation of the ataxia telangiectasia mutated (ATM)-p53-p21 and ATM-checkpoint kinase inhibitor 1 (Chk1)/Chk2-cell division cycle 25 (Cdc25) pathways. Revealing the mechanisms of cell cycle dysregulation associated with Ni exposure may help in the prevention and treatment of Ni-related carcinogenicity and toxicology.

Nickel carcinogenesis mechanism: cell cycle dysregulation

Scientists anxiously follow instances of heavy metals augmenting in the environment and undergoing bioaccumulation and trace their biomagnification across food webs, wary of their potent toxicity on biological entities Engineered nanoparticles supplement natural pools of respective heavy metals and can mimic their effects, exerting toxicity at higher concentrations Thus, a thorough understanding of the underlying mechanism of this precarious interaction is mandatory Most urban and industrial environments contain considerable quantities of nickel oxide nanoparticles These in excess can cause considerable damage to plant metabolism through a significant increase in cellular reactive oxygen species and perturbation of its cross-talk with the reactive nitrogen species In the present work, the authors have demonstrated how the intrusion of nickel oxide nanoparticles (NiO-NP) affected the exposed roots of Allium cepa: starting with disruption of cell membranes, before being interiorized within cell organelles, effectively disrupting cellular homeostasis and survival A major shift in the reactive oxygen species (ROS) and nitric oxide (NO) equanimity was also observed, unleashing major altercations in several crucial biochemical profiles Altered antioxidant contents and upregulation of stress-responsive genes, namely, Catalase, Ascorbate peroxidase, Superoxide dismutase, and Rubisco activase, showing on average 50-250% rise across NiO-NP concentrations tested, also entailed increased cellular hydrogen peroxide contents, with tandem rise in cellular NO Increased NO content was evinced from altered concentrations of nitric oxide synthase and nitrate reductase, along with NADPH oxidase, when compared with the negative control Though initially showing a dose-dependent concomitant rise, a significant decrease of NO was observed at higher concentrations of NiO-NP, while cellular ROS continued to increase Modified K/Na ratios, with increased proline concentrations and GABA contents, all hallmarks of cellular stress, correlated with ROS-NO perturbations Detailed studies showed that NiO-NP concentration had a significant role in inducing toxicity, perturbing the fine balance of ROS-NO, which turned lethal for the cell at higher dosages of the ENP precipitating in the accumulation of stress markers and an inevitable shutdown of cellular mechanisms

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Effect of Engineered Nickel Oxide Nanoparticle on Reactive Oxygen Species-Nitric Oxide Interplay in the Roots of Allium cepa L.

Hydrothermal vs microwave nanoarchitechtonics of carbon dots significantly affects the structure, physicochemical properties, and anti-cancer activity against a specific neuroblastoma cell line.

Nickel is an industrial and environmental toxic metal, which is toxic to humans in certain forms at high doses. Here, we investigated the cytotoxic effects of nickel sulfate (NiSO4) exposure on the human thyroid follicular epithelial cells (Nthy-ori 3-1) and its underlying toxicological mechanisms. The results showed that NiSO4 reduced the cell viability of Nthy-ori 3-1 cells in a dose- and time-dependent manner, inducing S and G2/M phases cell-cycle arrest and apoptosis. Electron microscopy demonstrated that abundant autophagic vacuoles were found in Nthy-ori 3-1 cells after NiSO4 treatment. Accordingly, exposure of Nthy-ori 3-1 cells to NiSO4 resulted in a dose-dependent increase of LC3II/I ratio, an induction of Beclin-1 expression, and a decrease in p62 levels. Blockade of autophagy with 3-methyladenine (3-MA) potentiated the NiSO4-induced apoptotic cell death, while induction of autophagy significantly alleviated toxicity of NiSO4. From a molecular standpoint, NiSO4 markedly promoted the activation of p38 and IKKβ by increasing their phosphorylation. In conclusion, we showed that autophagy was induced to protect thyroid cells from Ni2+ mediated apoptosis, thus providing rational strategy to prevent against nickel toxicity in the thyroid.

Nickel Sulfate Induces Autophagy in Human Thyroid Follicular Epithelial Cells

The use of nanomaterial-based products continues to grow with advancing technology. Understanding the potential toxicity of nanoparticles (NPs) is important to ensure that products containing them do not impose harmful effects to human or environmental health. In this study, we evaluated the comparative cytotoxicity between nickel oxide (NiO) and nickel hydroxide (Ni(OH)2) in human bronchoalveolar carcinoma (A549) and human hepatocellular carcinoma (HepG2) cell lines. Cellular viability studies revealed cell line-specific cytotoxicity in which nickel NPs were toxic to A549 cells but relatively nontoxic to HepG2 cells. Time-, concentration-, and particle-specific cytotoxicity was observed in A549 cells. NP-induced oxidative stress triggered dissipation of mitochondrial membrane potential and induction of caspase-3 enzyme activity. The subsequent apoptotic events led to reduction in cell number. In addition to cell death, suppression of cell proliferation played an essential role in regulating cell number. Collectively, the observed cell viability is a function of cell death and suppression of proliferation. Physical and chemical properties of NPs such as total surface area and metal dissolution are in agreement with the observed differential cytotoxicity. Understanding the properties of NPs is essential in informing the design of safer materials.

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Ethan T. Williams

Papers

Cytotoxicity of NiO and Ni(OH)2 Nanoparticles Is Mediated by Oxidative Stress-Induced Cell Death and Suppression of Cell Proliferation.

Graphene Defects in Saccharide Carbon Dots Govern Electrochemical Sensitivity