Molecular mechanism of nanomaterials induced liver injury: A review

Table 16 Effects and molecular mechanisms underlying hydroxyapatite nanoparticles induced hepatonanotoxicity

NPs	Size	Tested model	Dose & route of administration	Effects & mechanism	Ref.
Hydroxyapatite nanoparticles	50 nm (XRD)	HepG2 cells; L-02 cells	100 μg/mL for 24, 48 h	Caspase-3, 9 (activated); Bax, Bid (upregulated); Bcl-2 (downregulated); Cytosolic appearance of cytochrome c	[164]
				Apoptosis
Hydroxyapatite nanoparticles	80 nm (TEM)	BRL cells; Sprague–Dawley rat	25, 50, 100, 200, 400 and 800 μg/mL for 1 h; 50 mg/kg (Iv) single dose, sacrificed at 48 h	Decreased cell viability; Increased LDH leakage; Induced apoptosis & necrosis; MAPK signaling pathway activation; WBC count, ALT, AST, TNF-α, H2O2, MDA (increased); Infiltration of inflammatory cells near portal area	[165]
				Oxidative stress, inflammation, apoptosis, necrosis

ALT: Alkaline phosphatase; AST: Aspartate aminotransferase; Bax: Bcl-2 associated X protein; Bcl2: B-cell lymphoma 2; Bid: BH3 interacting-domain death agonist; H₂O₂: Hydrogen peroxide; LDH: Lactate dehydrogenase; MAPK: Mitogen activated protein kinase; MDA: Malondialdehyde; TNF-α: Tumor necrosis factor alpha.