Elsevier

Food and Chemical Toxicology

Volume 50, Issues 3–4, March–April 2012, Pages 641-647
Food and Chemical Toxicology

Nickel oxide nanoparticles induce cytotoxicity, oxidative stress and apoptosis in cultured human cells that is abrogated by the dietary antioxidant curcumin

https://doi.org/10.1016/j.fct.2012.01.017Get rights and content

Abstract

Nickel oxide nanoparticles (NiO NPs) are increasingly utilized in a number of applications. However, little is known about the toxicity of NiO NPs following exposure to human cells. This study was designed to investigate NiO NPs induced cytotoxicity, oxidative stress and apoptosis in cultured human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells. The results show that cell viability was reduced by NiO NPs and degree of reduction was dose-dependent. NiO NPs were also found to induce oxidative stress in dose-dependent manner indicated by depletion of glutathione and induction of reactive oxygen species and lipid peroxidation. Induction of caspase-3 enzyme activity and DNA fragmentation, biomarkers of apoptosis were also observed in NiO NPs exposed cells. Preventive potential of a dietary antioxidant curcumin against NiO NPs induced toxicity in HEp-2 MCF-7 cells was further examined. We found that co-exposure of curcumin significantly attenuated the cytotoxicity and oxidative stress induced by NiO NPs in both types of cells. This is the first report showing that NiO NPs induced ROS mediated cytotoxicity and apoptosis that is abrogated by curcumin. The pharmacological potential of curcumin against NiO NPs induced toxicity warrants further investigation.

Highlights

► NiO NP applications are accompanied by limited safety regulations & toxicity data. ► NiO NP-induced cytotoxicity and oxidative stress in HEp-2 and MCF-7 cells. ► NiO NP-induced caspapse-3 activation and DNA fragmentation in both types of cells. ► Curcumin attenuated NiO NP-induced cytotoxicity in both types of cells. ► Curcumin also ameliorated NiO NP-induced ROS & LPO generation and GSH depletion.

Introduction

Nanoparticles have received much attention due to not only their wide-spread applications, but also their adverse effects to the environmental and human health (Singh et al., 2009). Nickel oxide nanoparticles (NiO NPs) are increasingly used in various applications such as catalyst, gas sensor, alkaline battery cathode, electro-chromic film, magnetic material and fuel cell (Rao and Sunandana, 2008, Rani et al., 2010, Mu et al., 2011). Despite the many applications of NiO NPs, there are limited information concerning the toxicity of NiO NPs at the cellular and molecular level. Recent studies reported the toxic effects of NiO NPs in bacteria and microalgae (Baek and An, 2011, Gong et al., 2011). Horie et al. (2011) showed that NiO NPs have potential to induce oxidative stress related lung injury. However, Morimoto et al. (2011) reported that inhalation of NiO NPs did not induce the expressions of matrix metalloproteinase (MMP-2) and tissue inhibitor matrix proteinase (TIMP-2) mRNA levels in rat lungs.

Recent studies suggest that excessive production of reactive oxygen species (ROS) and oxidative stress could be one of the possible mechanisms of nanoparticle toxicity (Nel et al., 2006, Asharani et al., 2009, Ahamed et al., 2011). ROS in general cause DNA damage, including a multitude of oxidized base lesions, abasic sites, single and double-strand breaks; all of these can be cytotoxic, genotoxic or mutagenic (Ahamed et al., 2008, Zhan et al., 2010). Earlier, we also observed that inorganic nanoparticles induce ROS mediated cytotoxicity, DNA damage and apoptosis in cultured mammalian cells and Drosophila melanogaster (Ahamed et al., 2008, Ahamed et al., 2010a, Ahamed et al., 2010b, Ahamed et al., 2010c, Ahamed et al., 2011, Ahamed, 2011b, Ahamed et al., 2011c).

Curcumin is a widely used spice and coloring agent in food. It is extracted from the powdered dry rhizome of turmeric (Curcuma longa L.), a perennial herb widely cultivated in tropical regions of Asia. Curcumin is known to have multiple pharmacological properties such as anti-carcinogenic, anti-inflammatory and antioxidant (Dai et al., 2009, Ghosh et al., 2009, Prakobwong et al., 2011). However, the preventive potential of curcumin against nanoparticles toxicity has not been explored. This study was designed to investigate NiO NPs induced cytotoxicity, oxidative stress and apoptosis in human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells. The preventive potential of curcumin against NiO NPs induced toxicity was further examined. In this study we choosen two distinct cell types; human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells. HEp-2 cells derived from laryngeal epithelium and represent the first level of nanoparticles/pollutants exposure. To avoid the cell type specific response, we also used MCF-7 cells to compare the toxic response of NiO NPs from HEp-2 cells. Both HEp-2 and MCF-7 cell lines have been widely used in toxicological studies (Fahmy and Cormier, 2009, Wei et al., 2010).

Section snippets

Nickel oxide nanoparticles and reagents

Nickel (II) oxide (NiO) nanopowder [Product No.: 637130, APS:<50 nm (BET) and purity: 99.8% trace metal basis] was purchased from Sigma–Aldrich (St. Louis, Missouri). Fetal bovine serum (FBS), penicillin–streptomycin, DMEM/F-12 medium, HBSS was bought from Invitrogen Co. (Carlsbad, California). MTT [3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide], curcumin, reduced glutathione (GSH), 5,5-dithio-bis-(2-nitrobenzoic acid) (DTNB) and thiobarbituric acid (TBA) were obtained from

Characterization of nickel oxide nanoparticles

We utilized XRD, FETEM and DLS techniques to characterize NiO NPs. The crystalline nature of NiO NPs was confirmed by XRD (Fig. 1A). Fig. 1B shows the typical TEM image of NiO NPs. The average particle size of NiO NPs calculated by TEM and XRD was around 22 nm. Fig. 1C represents frequency of size distribution of NiO NPs. The average hydrodynamic size of NiO NPs in cell culture medium determined by DLS was around 151 nm (Fig. 1D). The higher size of nanoparticles in hydrodynamic state as compared

Discussion

In the present study, NiO NPs induced cytotoxicity in dose-dependent manner in cultured human airway epithelial (HEp-2) and human breast cancer (MCF-7) cells. ROS generation and oxidative stress has been cited to be one of the possible mechanisms of toxicity related to nanoparticle exposure (Nel et al., 2006, Wise et al., 2010). We also observed that NiO NPs induce oxidative stress in HEp-2 and MCF-7 cells. ROS and LPO levels were significantly higher while GSH level was significantly lower in

Conflict of Interest

The authors declare that there are no conflicts of interest.

Acknowledgments

This research was funded by King Abdulaziz City for Science and Technology (KACST), Riyadh, Saudi Arabia under the National Plan for Science and Technology (NPST) (Grant No.: 10-NAN1201-02).

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