Zinc toxicity

About: Zinc toxicity is a research topic. Over the lifetime, 727 publications have been published within this topic receiving 34583 citations. The topic is also known as: zinc poisoning.

Effect of selected heavy metals on the histopathology of different tissues of earthworm Eudrillus eugeniae.

Abstract: Laboratory-scale experiments were conducted to determine the effect of heavy metals viz. copper (Cu), cadmium (Cd), chromium (Cr), lead (Pb), and zinc (Zn) on the different vital tissues of earthworm Eudrillus eugeniae such as head, gizzard, clitellum, and intestine after the worms were placed in municipal solid waste (MSW) substrate spiked with heavy metals in the concentration range of 0.05 g/kg to 1.0 g/kg of the waste for Cu, Cr, PB, and Zn and 0.05 g/kg for Cd. The experiments were conducted for 100 days with periodic observations and sample collection for investigation after every 10th day. Copper and lead metals were found to cause more deleterious effect in head, gizzard, and intestine. Chromium metal caused cellular damage to the intestinal region. In comparison, cadmium metal severity was more than copper, lead, and chromium metal. Zinc metal did not show deleterious effect on tissues. In general, earthworms can be used as biomarkers in toxicity studies related to heavy metals at cellular levels.

Tissue Plasminogen Activator Alters Intracellular Sequestration of Zinc through Interaction with the Transporter ZIP4

Abstract: Glutamatergic neurons contain free zinc packaged into neurotransmitter-loaded synaptic vesicles. Upon neuronal activation, the vesicular contents are released into the synaptic space, whereby the zinc modulates activity of postsynaptic neurons though interactions with receptors, transporters and exchangers. However, high extracellular concentrations of zinc trigger seizures and are neurotoxic if substantial amounts of zinc reenter the cells via ion channels and accumulate in the cytoplasm. Tissue plasminogen activator (tPA), a secreted serine protease, is also proepileptic and excitotoxic. However, tPA counters zinc toxicity by promoting zinc import back into the neurons in a sequestered form that is nontoxic. Here, we identify the zinc influx transporter, ZIP4, as the pathway through which tPA mediates the zinc uptake. We show that ZIP4 is upregulated after excitotoxin stimulation of the mouse, male and female, hippocampus. ZIP4 physically interacts with tPA, correlating with an increased intracellular zinc influx and lysosomal sequestration. Changes in prosurvival signals support the idea that this sequestration results in neuroprotection. These experiments identify a mechanism via which neurons use tPA to efficiently neutralize the toxic effects of excessive concentrations of free zinc.

Effects of zinc on SN56 cholinergic neuroblastoma cells

Abstract: Zinc is a trace element necessary for proper development and function of brain cells. However, excessive accumulation of zinc exerts several cytotoxic effects in the brain. The aim of this work was to see whether cytotoxic effects of zinc are quantitatively correlated with changes in acetyl-CoA metabolism. The zinc levels up to 0.20 mmol/L caused concentration-dependent inhibition of pyruvate dehydrogenase (PDH) activity that correlated with the increase in trypan blue-positive fraction and the decrease in cultured cell number (r = 0.96, p = 0.0001). Chronic exposure of cells to 0.15 mmol/L zinc decreased choline acetyltransferase and aconitase activities, cytoplasmic acetyl-CoA and whole cell ATP level by 38%, 57%, 35%, and 62%, respectively but caused no change in mitochondrial acetyl-CoA level and activities of other enzymes of glycolytic and tricarboxylic acid cycle. dl-alpha-lipoamide when added simultaneously with zinc to cultured cells or their homogenates attenuated its chronic or acute suppressive effects. In homogenates of chronically Zn-treated cells, lipoamide overcame PDH but not aconitase inhibition. Presented data indicate that acute-transient elevation of zinc caused reversible inhibition of PDH, aconitase activities and acetyl-CoA metabolism, which when prolonged could lead to irreversible enzyme inactivation yielding decrease in cell viability and secondary suppression of their cholinergic phenotype.

Can the soil bacterium Cupriavidus necator sense ZnO nanomaterials and aqueous Zn2+ differentially?

Abstract: Synthetic metal oxide nanomaterials exert toxicity via two general mechanisms: release of free ions at concentrations which exert toxic effects upon the target cell, or specific surface-mediated physicochemical processes leading to the formation of hydroxyl free radicals and other reactive oxygen species which act to disrupt cell membranes and organelles. From a regulatory standpoint this presents a potential problem since it is not trivial to detect free metal ions in the presence of nanoparticles in biological or natural media. This makes efforts to identify the route of uptake difficult. Although in vitro studies of zinc oxide nanoparticles suggest that toxicity to the soil bacterium Cupriavidus necator is exerted in a similar manner to zinc acetate, we found no free Zn ion is associated with nanoparticle suspensions. The proteome of cells subjected to equal concentrations of either the nanoparticle or zinc acetate suggest that the mode of toxicity is quite different for the two forms of Zn, with a number of membrane-associated proteins up-expressed in response to nanoparticle exposure. Our data suggests that nanoparticles act to interrupt cell membranes thereby causing cell death rather than exerting a strictly toxic effect. We also identify potentially useful genes to serve as biomarkers of membrane disruption in toxicogenomic studies with nanoparticles or to engineer biosensor organisms.

Zinc induces motor neuron death via a selective inhibition of brain-derived neurotrophic factor activity

Abstract: Amyotrophic lateral sclerosis is a debilitating disease that results from the deterioration and loss of motor neurons. The neurotoxic potential of Zn(2+), both in vitro and in vivo, has been well established; however, the mechanism(s) of zinc's toxicity remain unclear. Our laboratory has demonstrated that Zn(2+)-mediated inhibition of neurotrophins can induce cell death. The present study investigates the neurotoxic mechanism(s) of this metal ion by assessing zinc's selectivity in altering the neurotrophin BDNF, but not the neural cytokine CNTF, with respect to motor neuron survival. Embryonic day 15 rat spinal motor neuron cultures were maintained in either BDNF or CNTF. Terminal deoxynucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) staining showed that exposure to 100microM Zn(2+) significantly increased the number of pro-apoptotic neurons in cultures maintained with BDNF, while these conditions had no effect on cultures maintained with CNTF. We also demonstrate that BDNF protomer cross-linking efficiency and TrkB receptor cross-linking to BDNF are significantly inhibited by Zn(2+), suggesting that a Zn(2+)-induced change in BDNF conformation inhibits receptor-binding activity. This study reveals a mechanism by which zinc toxicity is mediated via a selective loss in neurotrophin activity resulting in motor neuron death.