A review of mammalian toxicity of ZnO nanoparticles

Figures & data

Table 1 Overview of in vitro studies using zinc oxide nanoparticles

Cell type	Species	Cytotoxicity	Reactive oxygen species	Oxidative stress	Ca^2+ flux	Mitochondrial membrane potential	Membrane integrity	Apoptosis	IL-8	Zn^2+	References
Airways
A549 alveolar epithelial	H	+	+	+				+	+	+ (b)	^Citation5,Citation30,Citation35
BEAS-2B bronchial epithelial	H	+	+	+	+	+	+	+	+		^Citation28,Citation31,Citation32
Primary bronchial epithelial	H								+		^Citation32
Skin
Primary dermal fibroblasts	H							+			^Citation39
NCTC2544 keratinocytes	H		+			+					^Citation41
Digestive tract
LoVo colon carcinoma	H	+				+		+	+		^Citation44
Immune system
Monocytes	H	+	+	+							^Citation45
Lymphocytes	H	+	+	+							^Citation45
RAW264.7 macrophages	M				+	+	+				^Citation28
Ana-1 macrophages	M	+								+ (b)	^Citation47
Miscellaneous
Jurkat leukemia	H	+	NEG					+ (a)			^Citation48
H1355 lung carcinoma	H	+				+		+			^Citation13
Primary cardiac microvascular endothelial	H	+	+					+			^Citation49
NIH3T3 fibroblasts	M	+									^Citation50
HepG2 hepatocellular carcinoma	H	+	+								^Citation51
IP15 glomerular mesangial	H	+	+							+ (c)	^Citation53
HK-2 proximal epithelial	H	+	+								^Citation53
Embryonic lung fibroblast	H	+									^Citation54
Primary airway smooth muscle	H	+								+ (c)	^Citation57

Notes: (a) Caspase-independent; (b) effect was also shown for Zn²⁺ ions; (c) effect was also shown for zinc oxide microparticles.

Abbreviations: H, human; M, mouse; +, effect shown; NEG, shown not to be involved.

Figure 1 Putative mechanisms underlying the in vitro effects of ZnO NPs.

Notes: ZnO NPs dissolve in the extracellular milieu, resulting in an increased extracellular [Zn²⁺]. This in turn leads to an increased intracellular [Zn²⁺], resulting in reduced activity of Zn²⁺-dependent enzymes and Zn²⁺-dependent transcription factors. This mechanism has been suggested for A549 and BEAS-2B cells. Alternatively, ZnO NPs enter the cell, after which they dissolve intracellularly. This mechanism may apply to RKO cells. In lysosomes, ZnO NPs are dissolved, the low pH and lysosomal enzymes aiding in digestion of the protein corona. This leads to an increased intralysosomal [Zn²⁺], resulting in lysosomal destabilization. Toxic effects of ZnO NPs include intracellular Ca²⁺ flux, ROS generation, membrane damage, and mitochondrial dysfunction.
Abbreviations: L, lysosome; N, nucleus; NPs, nanoparticles; ROS, reactive oxygen species.

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