Molecular mechanism of nanomaterials induced liver injury: A review

Table 5 Effects and molecular mechanisms underlying ZnONPs induced hepatonanotoxicity

NPs	Size	Tested model	Dose & route of administration	Effects & mechanism	Ref.
ZnO NPs	Micro size; Nano size 63 nm (SEM)	Sprague Dawley rat	5, 50, 300, 100, 2000 mg/kg b.w for 14 d (oral)	AST, ALT (increased)	[20]
ZnO NPs	35 nm (TEM)	Wistar albino rats	2 mg/kg b.w. for 21; Days (i.p.)	Histopathological alterations; Kupffer cell activation	[106]
				Inflammation
ZnO NPs	50 nm (TEM)	Wistar albino rats	600 mg/kg/b.w and 1 g/kg/b.w for 5 d	ALT, NO, TNF-α, IL-6, CRP, IgG (increased)	[107]
				Inflammation
ZnO NPs	80 nm (TEM)	C57BL/6 mice	200 mg/kg/d (low dose) and 400 mg/kg/d (high dose) for 90 d (oral)	ALT, AST (increased); grp78, grp94, pdi-3, xbp-1(increased ER stress related proteins); Increased phosphorylation of PERK & eIF2α; caspase-3, 9, 12 (apoptosis); phosphorylation of JNK, and CHOP/GADD153; upregulation of Chop, Bax	[105]
				ERstress mediated activation of apoptotic pathway
ZnO NPs	30 nm (TEM)	HepG2 cell	14–20 μg/mL for 12 h	AST, ALT, Bax (increased) Bcl2 (decreased) LDH leakage; JNK, P38 activation	[108]
				Apoptosis
ZnO NPs	Less than 15 nm (TEM)	Sprague dawley albino rats	100, 200, 300 mg/kg b.w. per day for 14 d (oral)	ALT, AST, ALP (increased); Bax, caspase-3 (increased); Bcl2 (decreased); Modulation of JNK/p38MAPK & STAT-3 signalling pathways	[109]
				Apoptosis
ZnO NPs	20-50 nm (TEM)	HepG2 cells; sprague dawley rat	20 μg/mL for 24 h; 25 mg/kg b.w. for 7 d (i.p.)	Cell inactivation; Intracellular calcium overload; Mitochondrial damage	[110]
				Oxidative stress

ALP: Alkaline phosphatase, ALT: Alanine aminotransferase, AST: Aspartate aminotransferase, Bax: Bcl-2 associated X protein, Bcl2: B-cell lymphoma 2, CHOP: C/EBP Homologous Protein, CRP: C reactive protein, IgG: Immunoglobulin G, eIF2α: Eukaryotic initiation factor 2 α, GADD153: Growth arrest and DNA damage 153, Grp 78/94: Glucose regulated protein 78/94, IgG: Immunoglobulin G, IL-6: interleukin 6, JNK: Jun N-terminal kinase, LDH: Lactate dehydrogenase, MAPK: Mitogen activated protein kinase, NO: Nitric oxide, p38: Protein kinase, pdi-3: Protein disulfide isomerase -3, PERK: Protein kinase RNA like ER kinase, STAT-3: Signal transducer and activator of transcription 3, TNF-α: Tumor necrosis factor α, IL-6: Interleukin 6; xbp-1: X box binding protein-1.