Mechanisms of nanosilver-induced toxicological effects: more attention should be paid to its sublethal effects

Abstract

Due to its unique physicochemical properties and remarkable antimicrobial activity, nanosilver (nAg) is increasingly being used in a wide array of fields, including medicine and personal care products. Despite substantial progress being made towards the understanding of the acute toxicity of nAg, large knowledge gaps still exist on the assessment of its chronic toxicity to humans. Chronic effects of nAg, typically at low doses (i.e. sublethal doses) should be different from the acute toxicity at high doses (i.e., lethal doses), which is analogous to other environmental pollutants. Although a few review papers have elaborated the findings on nAg-mediated toxicity, most of them only discussed overt toxicity of nAg at high-level exposure and failed to evaluate the chronic and cumulative effects of nAg at sublethal doses. Therefore, it is necessary to more stringently scrutinize the sublethal toxicity of nAg under environmentally relevant conditions. Herein, we recapitulated recent findings on the sublethal effects of nAg toxicity performed by our groups and others. We then discussed the molecular mechanisms by which nAg exerts its toxicity under low concentrations and compared that with nAg-induced cell death.

Silver nanoparticle-induced hemoglobin decrease involves alteration of histone 3 methylation status

“…It should be stated that the dose of AgNPs exposed to humans is expected to be low under the environmental or daily-life setting. However, most previous studies looked into overt toxic effects of AgNPs with high-dose exposure, and did not evaluate the biological effects under sublethal exposure, which is more relevant to the real life situations [42]. Moreover, the current understanding of the mechanisms responsible for AgNP-induced cytotoxicity mainly derives from experiments with high-dose exposure, such as oxidative stress and Ag ion-mediated toxicities [54,55].…”

“…These mechanisms may not accurately reflect the biological effects induced by AgNPs at low doses [42]. Therefore, more attention should be paid to investigate the biological effects of AgNPs under low concentrations (at least sublethal concentrations which do not elicit significant damage to cell survival) [42]. This would help in identifying the hazards of AgNPs under the environmental and daily-life exposure settings [42].…”

“…Moreover, the current understanding of the mechanisms responsible for AgNP-induced cytotoxicity mainly derives from experiments with high-dose exposure, such as oxidative stress and Ag ion-mediated toxicities [54,55]. These mechanisms may not accurately reflect the biological effects induced by AgNPs at low doses [42]. Therefore, more attention should be paid to investigate the biological effects of AgNPs under low concentrations (at least sublethal concentrations which do not elicit significant damage to cell survival) [42].…”

“…Therefore, more attention should be paid to investigate the biological effects of AgNPs under low concentrations (at least sublethal concentrations which do not elicit significant damage to cell survival) [42]. This would help in identifying the hazards of AgNPs under the environmental and daily-life exposure settings [42]. We recently demonstrated that AgNPs could directly bind to RNA polymerase, leading to interruption of the transcription machinery and thus a drop of overall RNA synthesis in MEL cells at low concentrations without triggering detectable ROS [26].…”

“…Since dissolved silver ions (Ag ions) play a major role in the overt toxicity induced by AgNPs [42], we looked into the likely effects from Ag ions. The measurement of particle dissolution showed that the rate of Ag ion release was less than 10% in culture medium for 72 h (Fig.…”