Silver nanoparticles are used in many commercial products in daily life. Exposure to nanosilver has hepatotoxic effects in animals. This study investigated the cytotoxicity associated with polyvinylpyrrolidone-coated nanosilver (23.44 ± 4.92 nm in diameter) exposure in the human hepatoma cell line (HepG2) and normal hepatic cell line (L02), and the molecular mechanisms induced by nanosilver in HepG2 cells. Nanosilver, in doses of 20-160 μg mL-1 for 24 and 48 h, reduced cell viability in a dose- and time-dependent manner and induced cell membrane leakage and mitochondria injury in both cell lines; these effects were more pronounced in HepG2 cells than in L02 cells. Intracellular oxidative stress was documented by reactive oxygen species (ROS) being generated in HepG2 cells but not in L02 cells, an effect possibly due to differential uptake of nanosilver by cancer cells and normal cells. In HepG2 cells, apoptosis was documented by finding that ROS triggered a decrease in mitochondrial membrane potential, an increase in cytochrome c release, activation of caspase 3 and caspase 9, and a decrease in the ratio of Bcl-2/Bax. Furthermore, nanosilver activated the Fas death receptor pathway by downregulation of nuclear factor-κB and activation of caspase 8 and caspase 3. These results suggest that apoptosis induced by nanosilver in HepG2 cells is mediated via a mitochondria-dependent pathway and the Fas death receptor pathway. These findings provide toxicological and mechanistic information that can help in assessing the effects of nanosilver in biological systems, including the potential for anticancer activities.
Keywords: HepG2 cells; L02 cells; Nanosilver; apoptotic pathway; cytotoxicity.