ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress

Ahamed, Maqusood; Akhtar, Mohd Javed; Mohan, Ranjith; Ahmad, Iqbal; Siddiqui, M.K.J.; AlSalhi, Mohamad S.; Alrokayan, Salman A.

doi:10.1016/j.nano.2011.04.011

Cited by 210 publications

(113 citation statements)

References 39 publications

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“…In wild-type, the presence of metalloproteins provides antioxidant protection to the organism; this protection is significantly impaired in the triple knockout mutant, findings that mirror those of others (Sharma et al, 2012a,b;Ahamed et al, 2011;Sharma et al, 2009;Hanley et al, 2009;Huang et al, 2010).…”

Section: Resultssupporting

confidence: 73%

“…However, the exposure to ZnONPs resulted in a significant (p≤0.05) decrease in the total intracellular ROS levels in the wild-type strain, as the total fluorescence intensity of the DCF moiety decreased by 22% compared to the control levels. In , as hypothesized in studies that highlighted the carcinogenicity of ZnONPs (Sharma et al, 2012a,b;Ahamed et al, 2011;Sharma et al, 2009;Wu et al, 2010).…”

Section: Resultsmentioning

confidence: 82%

“…The harmful effects of ZnONPs are driven by their physicochemical properties (dissolution and formation rate, the morphology and chemical composition, surface reactivity, particle number) and the resulting physical damage caused by the aggregation and agglomeration of nanoparticles (Bai et al, 2010;Jiang et al, 2009;Zhang et al, 2010. The bio-kinetic behaviour and in vivo toxicity of ZnONP exposure has, to date, been investigated in several non-mammalian systems including in vitro cell-based assays (Sharma et al, 2012a,b;Ahamed et al, 2011;Wu et al, 2010), bacteria (Li et al, 2011;Reddy et al, 2007), algae (Franklin et al, 2007), plants (Lin and Xing, 2007), crustaceans (Poynton et al, 2011), fish (Bai et al, 2010), earthworms (Hooper et al, 2011) and nematodes (Khare et al, 2011;Ma et al, 2009;Ma et al, 2011;Roh et al, 2009;Wu et al, 2013). The nematode Caenorhabditis elegans, a powerful model organism due to the availability of a completely sequenced genome (Hillier et al, 2005) and many molecular genetics tools has been used in ecotoxicological research to study the molecular to organismal level responses to ROS and heavy metal challenges (Roh et al, 2006;Hughes and Sturzenbaum 2007;Swain et al, 2004Swain et al, , 2010Zeitoun-Ghandour et al, 2010; The roles of the metalloproteins metallothionein (MT) and phytochelatin (PC) are Furthermore, ZnONP mediated toxicity may result from the release of free ionic zinc (George et al 2010;Li et al, 2012;Poynton et al, 2011;Wang et al, 2009), which induces cellular damage via the generation of free reactive oxygen species (ROS), which in turn can promote pro-inflammatory effects Mocchegiani et al, 2011).…”

Section: Introductionmentioning

confidence: 99%

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Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans

Polak

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Jurkschat

et al. 2014

Comparative Biochemistry and Physiology Part C: Toxicology &

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Spurgeon, David J.; Sturzenbaum, Stephen R.. 2014. Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegansContact CEH NORA team at noraceh@ceh.ac.ukThe NERC and CEH trademarks and logos ('the Trademarks') are registered trademarks of NERC in the UK and other countries, and may not be used without the prior written consent of the Trademark owner. suggesting that the nominal exposure to pure ZnONPs represents in vivo, at best, a mixture exposure of ionic zinc and nanoparticles. Nevertheless, the analyzes provided evidence that the metallothioneins (mtl-1 and mtl-2), the pytochelatin synthase (pcs-1) and an apoptotic marker (cep-1) were transcriptionally activated. In addition, the DCFH-DA assay provided in vitro evidence of the oxidative potential of ZnONPs in the metal exposure sensitive triple mutant.Raman spectroscopy highlighted that the biomolecular phenotype changes significantly in the metal sensitive knockout worm upon ZnONP exposure, suggesting that these metalloproteins are instrumental in the protection against cytotoxic damage. Finally, ZnONP exposure was shown to decrease growth and development, reproductive capacity and lifespan, effects which were amplified in the triple knockout. By combining diverse toxicological strategies, we identified that individuals (genotypes) housing mutations in key metalloproteins are more susceptible to ZnONP exposure, which underlines the importance of fully functional metalloproteins to minimize ZnONP induced toxicity.

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Section: Resultssupporting

confidence: 73%

Section: Resultsmentioning

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans

Polak

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Jurkschat

et al. 2014

Comparative Biochemistry and Physiology Part C: Toxicology &

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“…35 Heat-shock protein 70 and p53 were induced. The pro-apoptotic protein bax was upregulated, while the antiapoptotic proteins survivin and bcl-2 were downregulated.…”

Section: +mentioning

confidence: 99%

A review of mammalian toxicity of ZnO nanoparticles

Vandebriel¹,

Jong²

2012

NSA

435

247

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This review summarizes the literature on mammalian toxicity of ZnO nanoparticles (NPs) published between 2009 and 2011. The toxic effects of ZnO NPs are due to the compound's solubility. Whether the increased intracellular [Zn 2+ ] is due to the NPs being taken up by cells or to NP dissolution in medium is still unclear. In vivo airway exposure poses an important hazard. Inhalation or instillation of the NPs results in lung inflammation and systemic toxicity. Reactive oxygen species (ROS) generation likely plays an important role in the inflammatory response. The NPs do not, or only to a minimal extent, cross the skin; this also holds for sunburned skin. Intraperitoneal administration induces neurological effects. The NPs show systemic distribution; target organs are liver, spleen, lung, and kidney and, in some cases, the heart. In vitro exposure of BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells results in cytotoxicity, increased oxidative stress, increased intracellular [Ca 2+ ], decreased mitochondrial membrane potential, and interleukin (IL)-8 production. Decreased contractility of airway smooth muscle cells poses an additional hazard. In contrast to the results for BEAS-2B and A549 cells, in RKO colon carcinoma cells ZnO NPs and not Zn 2+ induce cytotoxicity and mitochondrial dysfunction. Short-term exposure of skin cells results in apoptosis but not in an inflammatory response, while long-term exposure leads to increased ROS generation, decreased mitochondrial activity, and formation of tubular intercellular structures. Macrophages, monocytes, and dendritic cells are affected; exposure results in cytotoxicity, oxidative stress, intracellular Ca 2+ flux, decreased mitochondrial membrane potential, and production of IL-1β and chemokine CXCL9. The NPs are phagocytosed by macrophages and dissolved in lysosomes. In vitro the Comet assay and the cytokinesis-blocked micronucleus assay show genotoxicity, whereas the Ames test does not. This is, however, not confirmed by in vivo genotoxicity assays. Protein binding results in increased stability.

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“…[16][17][18][19][20][21] While low doses of ZnO nanoparticles have not produced toxic effects in vivo, high concentrations can cause sudden death. Moreover, ZnO nanoparticles are one of the most toxic nanoparticles, with the lowest LD 50 (median lethal dose) value, among the engineered metal oxide nanoparticles currently used in research.…”

mentioning

confidence: 99%

The effect of ZnO nanoparticles on liver function in rats

Tang¹,

Xu²,

Rong³

et al. 2016

IJN

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Zinc oxide (ZnO) is widely incorporated as a food additive in animal diets. In order to optimize the beneficial effects of ZnO and minimize any resultant environmental pollution, ZnO nanoparticles are often used for delivery of the zinc. However, the possible toxic effects of ZnO nanoparticles, including effects on cytochrome P450 (CYP450) enzymes, have not been evaluated. In this study, we investigated the effect of ZnO nanoparticles, in doses used in animal feeds, on CYP450 enzymes, liver and intestinal enzymes, liver and kidney histopathology, and hematologic indices in rats. We found that liver and kidney injury occurred when the concentrations of ZnO nanoparticles in feed were 300–600 mg/kg. Also, liver mRNA expression for constitutive androstane receptor was suppressed and mRNA expression for pregnane X receptor was induced when feed containing ZnO nanoparticles was given at a concentration of 600 mg/kg. Although the expression of mRNA for CYP 2C11 and 3A2 enzymes was induced by ZnO nanoparticles, the activities of CYP 2C11 and 3A2 were suppressed. While liver CYP 1A2 mRNA expression was suppressed, CYP 1A2 activity remained unchanged at all ZnO nanoparticle doses. Therefore, it has been concluded that ZnO nanoparticles, in the doses customarily added to animal feed, changed the indices of hematology and blood chemistry, altered the expression and activity of hepatic CYP enzymes, and induced pathological changes in liver and kidney tissues of rats. These findings suggest that greater attention needs to be paid to the toxic effects of ZnO nanoparticles in animal feed, with the possibility that the doses of ZnO should be reduced.

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ZnO nanorod-induced apoptosis in human alveolar adenocarcinoma cells via p53, survivin and bax/bcl-2 pathways: role of oxidative stress

Cited by 210 publications

References 39 publications

Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans

Metalloproteins and phytochelatin synthase may confer protection against zinc oxide nanoparticle induced toxicity in Caenorhabditis elegans

A review of mammalian toxicity of ZnO nanoparticles

The effect of ZnO nanoparticles on liver function in rats

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