Molecular mechanism of nanomaterials induced liver injury: A review

Table 17 Effects and molecular mechanisms underlying quantum dots induced hepatonanotoxicity

NPs	Size	Tested model	Dose & route of administration	Effects & mechanism	Ref.
Cd/Se/Te QD705	12.3 ± 5.2 nm (TEM)	ICR mice	100 μL of 40 and 160 pmol (IV) sacrificed at 12 and 16 wk	ALT, AST (increased); GPx, HO-1, 8-oxo-dG (increased); Cu/Zn/Se (increased); SOD activity (decreased); GSH/GSSG; Unbalanced antioxidation systems; Trace metals, trace metal transporters; TNFα, IL-6 (increased)	[167]
				Oxidative stress and inflammation
CdSe QD	4 nm (TEM)	Kunming mice Hepa 1–6 cells	200 nMCdCl2, 20 nM & 200 nM QDs (acute) for 48 h (IP); 20 nMCdCl2, 5 nM & 10 nM QDs for 6 wk (chronic) (IP); 20 nM CdCl2, 5 nM, 10 nM and 20 nM QDs for 24 & 48 h	ROS, MDA (increased); GSH-Px (decreased); Enlarged central vein, disordered hepatic cords; Reduced cell size, condensation; Round and condensed macrophage	[166]
				Oxidative stress
Mn-doped ZnS QDs	3.8 ± 0.1 nm (TEM)	Kunming mice	1 & 5 mg/kg (QDs); 5 mg/kg (QDs PEG) (IV) for 7 da sacrificed on 8th & 28th day	QDs accumulated in mitichondia, lysosome, lipid droplets; No hepatic damage	[169]
CdTe QDs	2.2 nm (TEM)	AML 12; ICR mice	27.66, 41.49, 53.94, 70.12, 91.16 & 118.50 μg/mL for 24 & 48 h. 4.125, 8.25 and 16.5 mg/kg body weight (IV) once a week for 4 wk	LPO, MDA, SOD, CAT, P53, Bcl-2, Nrf2, HO-1 (increased); Bax (decreased); ATP concentration (decreased); Nrf2 signaling pathway activation	[170]
				Oxidative stress, apoptosis
CdTe QDs	7.3 ± 1.2 nm (TEM)	HepG2 cell	10 μg/mL containing 1 μg/mL of cadmium for 24 h	MMP disruption, mitochondrial swelling, increased intracellular ca2+ levels, impaired cellular respiration & decreased ATP synthesis; PGC-1α (increased)	[171]
				Mitochondrial toxicity & dysfunction
CdTe QDs	15.25 ± 0.34 nm (TEM)	BALB/c mice	0.4, 2, 5, 6, 7, and 10 mg/kg b.w (Iv) for 24 h; 5 mg/kg bw (Iv) 2 h, 24 h, 3 d, and 1 wk	Enlarged mitochondria with increment in number; Affects ETC complex & ATP synthesis energy metabolism impairment	[172]
				Mitochondrial dysfunction
CdSe/Zn-QD	7.1 nm (TEM)	L02 cells; C57BL/6 mice; NLRP3 knockout mice	5, 10, 20, 40, 80 nM, 24 and 48 h; 10 nmol/kg (IV) results at 2 wk	Dose-dependent decrease in cell viability pyroptosis; Caspase-1 activity(increased); NLRP3 inflammasome activation; mt ROS production (increased); Cytoplasmic Ca2+ (increased) levels ALT, AST, MPO, TNFα, IL-1β (increased); γ-GT (decreased)	[168]
				Oxidative stress and inflammation
Cd free indium -based QDs	4 nm (TEM)	Lister Hooded rats	12.5 & 50 mg/kg b.w. (Iv) for 24 h. 1 wk, 4 wk	ALT, AST, ALP (slightly increased); No hepatic damage	[25]
CdTe/CdS QDs	12 nm (TEM)	HL-7702; HepG2 cells	1- 32 nM for 48 h	Lysosomal internalization; Abnormal activation of lysosomal enzymes; ROS generation (increased); Autophagy	[3]
				Apoptosis independent nanotoxicity
CdTe QDs	15.25 ± 0.34 nm (TEM)	BALB/c mice	0.4, 2, 5, 6, 7, and 10 mg/kg b.w (Iv) for 24 h. 5 mg/kg b.w. (Iv)2 h, 24 h, 3 d (d), and 1 wk (w)	AST, ALT, T-bil (increased); Albumin (decreased); liver accumulation	[173]
CdTe QDs	15.25 ± 0.34 nm (TEM)	BALB/c mice	0.4, 2, 5, 6, 7, and 10 mg/kg b.w (Iv) for 24 h. 5 mg/kg b.w. (Iv) 2 h, 24 h, 3 d (d), and 1 wk (w)	tGSH, ATP (depletion) GST, CAT (decreased) SOD activity (increased); Hmox I, Ncf-1, Ncf-2 (upregulated expression); PGC-1α (increased)	[9]
				Oxidative stress, apoptosis
CdTe QDs	2.2-3.0 nm (TEM)	ICR mice; KUP5 cells	2.5 & 10 μM/kg· b.w. (Iv) single dose once per wekk for 14 d; 5, 50 & 500 NM	IL-1β, TNF-α, IL-6 (increased); Assembly of NLRP3 inflammasome; ROS productin (increased); Activation of NF-KB pathway; Kupffer cell activation	[174]
				Oxidative stress, Inflammation

8-oxo-dG: 8-oxo-7,8-dihydro-2¢-deoxyguanosine; ALP: Alkaline phosphatase; ALT: Alanine aminotransferase, AST: Aspartate aminotransferase, ATP: Adenosine triphosphate; Bax: Bcl-2 associated X protein; Bcl-2: B-cell lymphoma 2; CAT: Catalase; Cu-copper; ETC: Electron transport chain; GSH-Px: Glutathione peroxidase; GSSG: Glutathione disulfide; GST: Glutathione S-transferase; HO-1/Hmox I: Heme oxygenase 1; IL-1β: Interleukin 1 β; IL-6: Interleukin-6; LPO: Lipid peroxidation; MDA: Malondialdehyde; MMP: Mitochondrial membrane potential; MPO: Myeloperoxidase; Ncf-1,2: Neutrophil cytosolic factor 1,2; NF-κB: Nuclear factor kappa beta; NLRP3: NOD-like receptor protein 3; Nrf2: Nuclear factor erythroid 2-related factor 2; P53: Tumor suppressor protein p53; PGC-1α: Peroxisome proliferator-activated receptor gamma coactivator 1-alpha; ROS: Reactive oxygen species; Se: Selenium; SOD: Superoxide dismutase; T-Bil: Total bilirubin; tGSH: Total glutathione; TNFα: Tumor necrosis factor alpha; γ-GT: Gamma glutamyl transferase; Zn: Zinc.