Synergistic toxicity of zno nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to zno nanoparticles

Abstract

The extensive applications of ZnO nanoparticles (nano ZnO) and dimethoate (DM) have increased the risk of humans' co-exposure to nano ZnO and DM. Here, we report the synergistic effect of nano ZnO and DM on their biodistribution and subacute toxicity in mice. Nano ZnO and DM had a synergistic toxicity in mice. In contrast, bulk ZnO and DM did not cause an obvious synergistic toxicity in mice. Although nano ZnO was low toxic to mice, coexposure to nano ZnO and DM significantly enhanced DM-induced oxidative damage in the liver. Coadministration of nano ZnO with DM significantly increased Zn accumulation by 30.9 ± 1.9% and DM accumulation by 45.6 ± 2.2% in the liver, respectively. The increased accumulations of DM and Zn in the liver reduced its cholinesterase activity from 5.65 ± 0.32 to 4.37 ± 0.49 U/mg protein and induced hepatic oxidative stress. Nano ZnO had 3-fold or 2.4-fold higher binding capability for serum albumin or DM, respectively, than bulk ZnO. In addition, serum albumin significantly increased the binding capability of nano ZnO for DM by approximately four times via the interaction of serum albumin and DM. The uptake of serum albumin- and DM-bound nano ZnO by the macrophages significantly increased DM accumulation in mice. Serum albumins play an important role in the synergistic toxicity of nano ZnO and DM. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 1202-1212, 2017.

Understanding Nanomaterial–Liver Interactions to Facilitate the Development of Safer Nanoapplications

“…[ 50 ] Similarly, ZnO NPs co‐administered with the xenobiotic compound, organophosphate dimethoate, increased hepatic deposition of zinc and dimethoate, resulting in increased liver oxidative stress and liver injury. [ 72 ] Non‐alcoholic fatty liver disease (NAFLD) is a chronic liver condition that is characterized by the excessive fatty acid accumulation in hepatocytes without alcohol abuse. [ 73 ] Metal NMs including Au, Ag, and Si NPs have been found to worsen NAFLD through increased inflammation or hepatocellular damage in various mouse models.…”

The role of toxic stimuli combinations in determining safe exposure limits

“…Female mice were exposed to rat proximity-induced stress and subthreshold doses of BPA. The combination of rat-exposure stress and BPA significantly disrupted implantation and increased uterine luminal area, whereas either manipulation on its own did not.“Synergistic toxicity of ZnO nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to ZnO nanoparticles” [17]. Although nanoZnO had low toxicity to mice, co-exposure to nanoZnO and DM significantly enhanced DM-induced oxidative damage in the liver.“Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats” [18].…”

“…“Synergistic toxicity of ZnO nanoparticles and dimethoate in mice: Enhancing their biodistribution by synergistic binding of serum albumin and dimethoate to ZnO nanoparticles” [17]. Although nanoZnO had low toxicity to mice, co-exposure to nanoZnO and DM significantly enhanced DM-induced oxidative damage in the liver.…”

All Roads Lead to the Liver: Metal Nanoparticles and Their Implications for Liver Health

“…[155] Interestingly, this interaction was only found to be induced by zinc oxide NPs (spherical: 29.5 nm) and not bulk zinc oxide (rod-shaped: 80-600 nm). [156] Serum albumin coating was found to increase dimethoate-zinc oxide NP binding fourfold, suggesting a possible mechanism for increased dimethoate deposition after zinc oxide NP interaction with body components. [156] LPS are endotoxins that are potent activators of Kupffer macrophages, triggering the release of inflammatory signals such as TNF-α, resulting in increased liver inflammation.…”

“…[156] Serum albumin coating was found to increase dimethoate-zinc oxide NP binding fourfold, suggesting a possible mechanism for increased dimethoate deposition after zinc oxide NP interaction with body components. [156] LPS are endotoxins that are potent activators of Kupffer macrophages, triggering the release of inflammatory signals such as TNF-α, resulting in increased liver inflammation. [157,158] Several papers have exploited the redox properties of cerium oxide NPs against LPS-induced oxidative stress, reducing inflammation and demonstrating a strong protective effect against liver damage.…”