Zinc-Oxide Nanoparticles Exhibit Genotoxic, Clastogenic, Cytotoxic and Actin Depolymerization Effects by Inducing Oxidative Stress Responses in Macrophages and Adult Mice

Zinc oxide nanoparticles (ZnO-NPs) have wide biological applications, which have raised serious concerns about their impact on the health and environment. Although, various studies have shown ZnO-NP toxicity on different cells under in vitro conditions, sufficient information is lacking regarding toxicity and underlying mechanisms under in vivo conditions. In this work, we investigated genotoxic, clastogenic, and cytotoxic effects of ZnO-NPs on macrophages and in adult mice. ZnO-NP-treated mice showed signs of toxicity such as loss in body weight, passive behavior and reduced survival. Further mechanistic studies revealed that administration of higher dose caused severe DNA damage in peripheral blood and bone marrow cells as evident by the formation of COMET tail, micronuclei, chromosomal fragmentation, and phosphorylation of H2A histone family member X. Moreover, ZnO-NPs inhibited DNA repair mechanism by downregulating the expression of fen-1 and polB proteins. Histopathological examinations showed severe inflammation and damage to liver, lungs, and kidneys. Cell viability and wound healing assays revealed that ZnO-NPs killed macrophages in a dose-dependent manner, caused severe wounds and inhibited cellular migration by irreversible actin depolymerization and degradation. Reduction in the viability of macrophages was due to the arrest of the cell cycle at the G0/G1 phase, inhibition of superoxide dismutase and catalase and eventually reactive oxygen species. Furthermore, tr...
Source: Toxicological Sciences - Category: Toxicology Authors: Tags: Zinc Oxide Nanoparticle and Integrity of DNA and Cytoskeleton Source Type: research