The unique physicochemical properties inherent to nanoscale materials have unveiled numerous potential applications, spanning beyond the pharmaceutical and medical sectors into various consumer industries like food and cosmetics. Consequently, humans encounter nanomaterials through diverse exposure routes, giving rise to potential health considerations. Noteworthy among these materials are silica and specific metallic nanoparticles, extensively utilized in consumer products, which have garnered substantial attention due to their propensity to accumulate and induce adverse effects in the liver. This review paper aims to provide an exhaustive examination of the molecular mechanisms underpinning nanomaterial-induced hepatotoxicity, drawing insights from both in vitro and in vivo studies. Primarily, the most frequently observed manifestations of toxicity following the exposure of cells or animal models to various nanomaterials involve the initiation of oxidative stress and inflammation. Additionally, we delve into the existing in vitro models employed for evaluating the hepatotoxic effects of nanomaterials, emphasizing the persistent endeavors to advance and bolster the reliability of these models for nanotoxicology research.

The unique physicochemical properties of materials at nanoscale have opened a plethora of opportunities for applications in the pharmaceutical and medical field, but also in consumer products from food and cosmetics industries. As a consequence, daily human exposure to nanomaterials through distinct routes is considerable and, therefore, may raise health concerns. Many nanomaterials have been described to accumulate and induce adversity in the liver. Among these, silica and some types of metallic nanoparticles are the most broadly used in consumer products and, therefore, the most studied and reported. The reviewed literature was collected from PubMed.gov during the month of March 2020 using the search words "nanomaterials induced hepatotoxicity", which yielded 181 papers. This present paper reviews the hepatotoxic effects of nanomaterials described in in vitro and in vivo studies, with emphasis on the underlying mechanisms. The induction of oxidative stress and inflammation are the manifestations of toxicity most frequently reported following exposure of cells or animal models to different nanomaterials. Furthermore, the available in vitro models for the evaluation of the hepatotoxic effects of nanomaterials are discussed, highlighting the continuous interest in the development of more advanced and reliable in vitro models for nanotoxicology.

Studies have demonstrated that nano NiO could induce liver toxicity in rats, but its mechanism remains unclear. This study aimed to explore the role of the NF-κB signaling pathway in rat liver toxicity after nano NiO exposure. Male Wistar rats were exposed to nano NiO (0.015, 0.06 and 0.24 mg per kg b.w.) and micro NiO (0.24 mg per kg b.w.) by intratracheal instillation twice a week for 6 weeks. To investigate the liver toxicity induced by nano NiO, the indicators of liver function and inflammatory response were detected, and the histopathological changes were observed. The levels of NF-κB signaling pathway related gene and protein expression were examined using RT-qPCR and western blot techniques in the liver tissue. The results showed that the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and gamma-glutamyltranspeptidase (GGT) increased after nano NiO exposure. Cellular edema, hepatic sinus disappearance, and neutrophil and lymphocyte infiltration were observed. Nano NiO increased the concentrations of pro-inflammatory cytokines (IL-1β and IL-6), but decreased the levels of anti-inflammatory cytokines (IL-4 and IL-10). It also induced the upregulation of TNF-α, NF-κB-inducible kinase (NIK), IκB kinase alpha (IKK-α) and NF-κB mRNA, while inducing the downregulation of the inhibitor kappa B (IκB) alpha. In addition, we found that the protein content of NIK, IKK-α, p-IKK-α, p-IκB-α and NF-κB was elevated, whereas that of IκB-α was reduced. The results indicated that the NF-κB signaling pathway played an important role in rat liver toxicity induced by nano NiO.