Molecular mechanism of nanomaterials induced liver injury: A review

Table 15 Effects and molecular mechanisms underlying nanoclay, NCD, polystyrene, chytosan induced hepatonanotoxicity

NPs	Size	Tested model	Dose & route of administration	Effects & mechanism	Ref.
Nano-Clay	57.8 ± 12.3 nm & 648.3 ± 232.2 nm	BALB/C mice	1, 5, 10, 20 mg/kg b.w. (Iv) 24 h; Co-administered with Ccl4, paraquat, cisplatin	ALT, AST (increased)	[163]
NCD (modified nanocellulose with oxalate esters)	100 nm (SEM)	Wistar rat	50 & 100 mg/kg b.w. (oral) for 7 d	ALT, AST (increased); CAT, GPx activity (decreased); MPO activity (increased); iNOS, Bax (increased); dialated sinusoidal space, vacuolated hepatocytes, cellular infiltration	[29]
				Oxidative stress
Polystyrene	PS NPs 158.8 ± 1.3 nm; aPS NPs 117.0 ± 1.8 nm (SEM)	ICR mice	50 mg/kg/d (oral) for 7 d	Glucose, HDL-C, TG, TC (increased in blood); LDL-C (decreased in blood); Activation of PI3K/AKT/GLUT4 & SREBP-1/PPARγ/ATGL signaling pathways; TG decomposition; Lipid accumulation (increased); Nuclear pyknosis, blurred intercellular space, central hepatic vein congestion, hepatic ballooning; Compared to PS NPs, aPS NPs showed higher toxicity	[28]
				Disruption of glycolipid metabolism
Chitosan (CsNPs)	18 ± 1 nm (DLS)	BHAL cell	≥ 0.5% w/v for 4 h	Readily internalized; Disrupt membrane integrity; ALT leakage; CYP3A4 enzyme activity (increased); necrotic or autophagic cell death	[27]

ALT: Alanine aminotransferase, aPS: UV aging Polystyrene, AST: Aspartate aminotransferase, ATGL: Adipose triglyceride lipase, Bax: Bcl-2 associated X protein, CAT: Catalase, CYP3A4: Cytochrome P4503A4, GLUT4: Glucose transporter 4, GPx: Glutathione peroxidase, HDL-C: High-density lipoprotein, iNOS: Inducible nitric oxide synthase, LDL-C: Low-density lipoprotein, MPO: Myeloperoxidase, NLRP3: NOD-like receptor protein 3, p-AKT: Phosphoprotein kinase B, PI3K: Phosphatidylinositol 3-kinase, PPARγ: Peroxisome proliferator-activated receptor-γ, PS: Polystyrene, ROS: Reactive oxygen species, SREBP-1: Sterol regulatory element binding protein-1, TC: Total cholesterol, TG: Triglyceride.