Susceptibility of Overweight Mice to Liver Injury as a Result of the ZnO Nanoparticle-Enhanced Liver Deposition of Pb²⁺

Abstract

The prevalence of the applications of nanomaterials in consumer products and water treatment facilities increases the chance that humans will be exposed to both nanoparticles and environmental pollutants such as heavy metals. Co-exposure to nanoparticles and heavy metals may adversely affect human health, especially in susceptible populations such as overweight subjects. To evaluate the impact of such co-exposures, we orally administered zinc oxide nanoparticles (ZNPs; 14 or 58 nm) and/or Pb(Ac) at tolerable doses to both healthy overweight and healthy normal weight mice. The ZNPs enhanced the deposition of Pb in all major organs in the overweight mice compared with that in the normal mice. As a result, higher levels of hepatic reactive oxygen species, pro-inflammatory cytokines, and liver injury were observed in the overweight mice but not in the normal weight mice. Our findings underscore a potentially enhanced risk of nanoparticle/heavy metal co-exposure in the susceptible overweight population.

Fetotoxicity of Nanoparticles: Causes and Mechanisms

“…The rapid development of nanotechnology has led to the increased production and use of nanomaterials in industry, biomedicine, and everyday life [1][2][3], thus highlighting the need for a rise in biosafety evaluation, especially for susceptible populations [4][5][6][7]. Among these, pregnant women and developing embryos/fetuses are more vulnerable to xenobiotics.…”

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

“…[144] It was found that titanium and lead deposition was increased in liver, kidney and brain tissue after co-treatment, further elevating liver ROS levels and impairing function. Obese mice subjected to lead acetate and zinc oxide NPs (14 and 58 nm) co-treatment showed greater levels of liver injury not observed in mice of healthy weight, [145] showing that obesity was a confounding third factor in the interplay between heavy metals and NPs. The example of these two heavy metals illustrates the danger of heavy metals and NPs converging together to induce greater toxicity, and emphasizes the hazard of liver NP accumulation.…”

A review of hepatic nanotoxicology – summation of recent findings and considerations for the next generation of study designs

“…The co-administration increased levels of heavy metal deposited in the liver by twofold. Jia et al (2017) also showed that ZnO NMs or ZnO/Pb exposure of mice receiving a normal diet resulted in negligible pathological damage. However, the same exposures in the high-fat diet mice induced significant liver injury in addition to the dietinduced hepatic steatosis.…”

“…Similarly, a reduction in SOD activity and a rise in MDA content of liver tissue was observed only in the high-fat diet mice after exposure to ZnO and Pb. Evidence indicated that the hepatic toxicity of NMs or co-administration was significantly augmented by preexisting hepatic disease initiated by the diet (Jia et al 2017). Shrivastava et al (2014) orally administered to 6-week-old male Swiss albino mice (25-30 g) a dose of 500 mg/kg of a ZnO (80-100 nm), TiO 2 (50-75 nm) or Al 2 O 3 (40-50 nm) for 21 consecutive days.…”