Co-exposure to silver nanoparticles and cadmium induce metabolic adaptation in HepG2 cells

Abstract

(2018) Co-exposure to silver nanoparticles and cadmium induce metabolic adaptation in HepG2 cells, Nanotoxicology, 12:7, 781-795, DOI: 10.1080/17435390.2018 Although multiple studies have reported the toxicological effects and underlying mechanisms of toxicity of silver nanoparticles (AgNP) in a variety of organisms, the interactions of AgNP with environmental contaminants such as cadmium are poorly understood. We used biochemical assays and mass spectrometry-based proteomics to assess the cellular and molecular effects induced by a co-exposure of HepG2 cells to AgNP and cadmium. Cell viability and energy homeostasis were slightly affected after a 4-h exposure to AgNP, cadmium, or a combination of the two; these endpoints were substantially altered after a 24-h co-exposure to AgNP and cadmium, while exposure to one of the two contaminants led only to minor changes. Proteomics analysis followed the same trend: while a 4-h exposure induced minor protein deregulation, a 24-h exposure to a combination of AgNP and cadmium deregulated 43% of the proteome. The toxicity induced by a combined exposure to AgNP and cadmium involved (1) inactivation of Nrf2, resulting in downregulation of antioxidant defense and proteasome-related proteins, (2) metabolic adaptation and ADP/ATP imbalance, and (3) increased protein synthesis possibly to reestablish homeostasis. The adaptation strategy was not sufficient to restore ADP/ATP homeostasis and to avoid cell death. ARTICLE HISTORY

Silver nanoparticle-induced expression of proteins related to oxidative stress and neurodegeneration in an in vitro human blood-brain barrier model

“…silver ions, released from the AgNPs present in the periphery (Hadrup and Lam 2014;Mirsattari et al 2004). In vitro studies on various mammalian cells report that AgNPs induce major cytotoxic actions leading to increased cellular apoptosis and cell death (Miethling-Graff et al 2014;Verano-Braga et al 2014;Miranda et al 2018). Other cellular responses, including changes in minor metabolic pathways and protein post-translational modifications, remain largely uninvestigated and may reveal novel actions of nanoparticle toxicity.…”

All Roads Lead to the Liver: Metal Nanoparticles and Their Implications for Liver Health

“…Several in vitro studies have reported that HepG2 cell viability decreased upon exposure to silver NPs. [127][128][129][130] Shanmugasundaram et al found that silver (spherical: 30.5 nm), gold (spherical: 14.5 nm), and silver-gold alloy NPs (spherical: 41.5 nm) conferred protection against DEN-induced HCC in rats through a reduction in tumor volume, blood hepatic biochemical markers and improvement in liver architecture. [131] Other papers have also reported that silver NPs reduce DENinduced HCC symptoms.…”

“…[143] Silver NPs (spherical: 8-20 nm) and cadmium chloride greatly reduced cell viability in HepG2 hepatocytes, possibly through increased oxidative stress from Nrf2 inactivation. [129] A second heavy metal, lead acetate, was co-administered together with titanium dioxide NPs (50 and 120 nm) to mice, and resulted in increased liver damage. [144] It was found that titanium and lead deposition was increased in liver, kidney and brain tissue after co-treatment, further elevating liver ROS levels and impairing function.…”

Microcellular Environmental Regulation of Silver Nanoparticles in Cancer Therapy: A Critical Review

“…This resulted in a significant alteration of protein ubiquitination are possibly increased toxicity. The eIF2 signaling pathway was modified after the AgNPs and Cd 2+ exposures, owing to the downregulation of ribosome subunits and proteins involved in translation initiation [141]. Collectively, microenvironmental oxidative stress has settled in several locations.…”