Effects of Long-Term Exposure to Zinc Oxide Nanoparticles on Development, Zinc Metabolism and Biodistribution of Minerals (Zn, Fe, Cu, Mn) in Mice

Abstract

Zinc oxide nanoparticles (nano-ZnOs) are widely used and possess great potentials in agriculture and biomedicine. It is inevitable for human exposure to these nanoparticles. However, no study had been conducted to investigate the long term effects of nano-ZnOs. This study aimed at investigating effects of nano-ZnOs on development, zinc metabolism and biodistribution of minerals (Zn, Fe, Cu, and Mn) in mice from week 3 to 35. After the characteristics of nano-ZnOs were determined, they were added into the basal diet at 0, 50, 500 and 5000 mg/kg. Results indicated that added 50 and 500 mg/kg nano-ZnOs showed minimal toxicity. However, 5000 mg/kg nano-ZnOs significantly decreased body weight (from week 4 to 16) and increased the relative weights of the pancreas, brain and lung. Added 5000 mg/kg nano-ZnOs significantly increased the serum glutamic-pyruvic transaminase activity and zinc content, and significantly enhanced mRNA expression of zinc metabolism-related genes, including metallothionein 1(32.66 folds), metallothionein 2 (31.42 folds), ZIP8 (2.21folds), ZIP14 (2.45 folds), ZnT1 (4.76 folds), ZnT2 (6.19 folds) and ZnT4 (1.82 folds). The biodistribution determination showed that there was a significant accumulation of zinc in the liver, pancreas, kidney, and bones (tibia and fibula) after receiving 5000 mg/kg nano-ZnO diet, while no significant effects on Cu, Fe, and Mn levels, except for liver Fe content and pancreas Mn level. Our results demonstrated that long term exposure to 50 and 500 mg/kg nano-ZnO diets showed minimal toxicity. However, high dose of nano-ZnOs (5000 mg/kg) caused toxicity on development, and altered the zinc metabolism and biodistribution in mice.

Effects of dietary zinc oxide nanoparticles supplementation on growth performance, zinc status, intestinal morphology, microflora population, and immune response in weaned pigs

“…Dietary supplemented 450 mg kg −1 nano‐ZnOs and 3000 mg kg −1 ZnO may downregulate the uptake of Zn at higher dosages to prevent toxicity. Wang et al . reported that Zn bioavailability decreased with increasing dietary nano‐ZnOs concentration due to the significantly increased fecal Zn concentration.…”

“…The novel properties of nanoparticles include small size, large specific surface area, high surface activity, more surface active centers, and high catalytic efficiency . Zinc oxide nanoparticles (nano‐ZnOs) are widely used and possess excellent potential in agriculture and biomedicine . Zinc oxide nanoparticles exhibit effective antimicrobial activity against E. coli and Staphylococcus aureus in vitro , which indicates that nano‐ZnOs may work as a potential alternative product for pig feeding and may contribute to lower zinc excretion in animal wastes .…”

Effect of pectin oligosaccharides and zinc chelate on growth performance, zinc status, antioxidant ability, intestinal morphology and short‐chain fatty acids in broilers

“…The micronutrient of Zn was essential for the development of tissues in the body, which was absorbed by the intestinal epithelial cells, transported in blood and finally accumulated in tissues such as pancreas (Wang, Lu et al, 2016). Zinc is involved in the biological processes of pancreas including the secretion of digestive enzymes as well as regulating Zn secretion (Kelleher, McCormick, Velasquez, & Lopez, 2011 to 20,000 mg/kg caused lesions in the pancreas of chicks (Dewar, Wight, Pearson, & Gentle, 1983).…”

Altered tissue mineralization, increased hepatic lipid and inhibited autophagy in intrauterine growth retardation piglets

“…All pigs were slaughtered via electrical stunning. Samples to determine mineral concentrations and mRNA expression were collected as described by Wang et al (2016). Briefly, lungs, heart, kidney, liver, and longissimus dorsi muscle (LDM) were collected and stored at -20 °C to determine mineral concentration.…”