Oral Exposure to Silver Nanoparticles or Silver Ions May Aggravate Fatty Liver Disease in Overweight Mice.

As the applications and environmental release of silver ions and nanoparticles are increasing, increasing human exposure to these pollutants has become an emerging health concern. The impeding effects of such pollutants on susceptible populations are severely under-studied. Here, we demonstrate that silver nanoparticles (Ag NPs), at a dose that causes no general toxicity in normal mice, promotes the progression of fatty liver disease from steatosis to steatohepatitis only in overweight mice. Exposure to Ag+ ions induces the same effects in overweight mice. Ag NPs rather than Ag+ ions cause this disease progression based on our findings that Ag+ ions are partly reduced to Ag NPs in fatty livers, and the toxic effect is correlated with the liver dose of Ag NPs, not Ag+ ions. Furthermore, the Ag NP-induced pro-inflammatory activation of Kupffer cells in the liver, enhancement of hepatic inflammation, and suppression of fatty acid oxidation are identified as key factors in the underlying mechanisms.