Effect of silver nanoparticles on mitogen-activated protein kinases activation: role of reactive oxygen species and implication in DNA damage

Abstract

Large quantities of engineered nanoparticles (NP), such as nanosilver (AgNP), have been widely applied, leading to an increased exposure and potential health concerns. Herein, we have examined the ability of AgNP to induce reactive oxygen species (ROS), their role in genotoxic effects and the involvement of mitogen-activated protein kinases (MAPK). AgNP exposure induced ROS production in human epithelial embryonic cells which could be decreased by diphenyleneiodonium (DPI), an inhibitor of NADPH oxidases. Extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation, induced by AgNP, was an early response but not sustained in time. Furthermore, JNK and ERK activation could be inhibited by both DPI and a free radicals scavenger N-acetyl cysteine. We also investigated the role of MAPK in the DNA damage. Using a modified comet assay for the specific detection of hOGG1 sensitive sites, we showed that AgNP induced DNA oxidation after 30-min treatment, whereas no response was observed after 2h. In conclusion, AgNP seem to induce DNA damage via a mechanism involving ROS formation. The oxidative DNA damage observed was transient, likely due to DNA repair; furthermore, higher damage was achieved upon inhibition of ERK activation by pre-treatment with U0126, suggesting a role for ERK in DNA damage repair. Activation of different MAPK might play an important role in the NP toxicity outcomes; understanding this process may be helpful for the identification of NP toxicity.

Silver nanoparticles induced neurotoxicity through oxidative stress in rat cerebral astrocytes is distinct from the effects of silver ions

“…One of the consequences of oxidative stress is the phosphorylation of MAPKs (Jayakumar et al, 2006) and JNKs promote apoptosis by the upregulating proapoptotic genes directly or by modulating the activities of mitochondrial pro-and anti-apoptotic proteins through distinct phosphorylation events (Danny et al, 2008). AgNPs exposure was found to induce ROS production in human epithelial embryonic cells and an early response of JNK phosphorylation (Rinna et al, 2015). In this study, significant increase in JNK phosphorylation concomitant with ROS generation was evidently involved in astrocytes apoptosis upon cytotoxic levels of AgNPs treatments (10 and 20 mg/mL).…”

Toxic effects of silver nanoparticles in mammals – does a risk of neurotoxicity exist?

“…DNA damage induced by ROS has been detected in vitro as increased DNA fragmentation in human alveolar cells [35], human liver cells [106], human epithelial embryonic cells [116], and in vivo in rodents [2,32,103] and aquatic organisms exposed to AgNPs [3,38].…”

Comet Assay on Toxicogenetics; Several Studies in Recent Years on Several Genotoxicological Agents

“…In the study of Rinna, Magdolenova et al, Comet assay is used for to detect the human 8-oxoguanine DNA N-glycosylase 1 hOGG1 and demonstrate the genotoxicity of gold naoparticles. They observed that AgNP induced DNA oxidation via a mechanism involving ROS formation after 30-min treatment, whereas the response was negative after 2h [44]. Woodruff et al, assessed the genotoxicity of 10 nm Titanium dioxide nanoparticles (TiO 2 -NPs) using Ames test and Comet assay.…”