Effects of Long-Term Dietary Zinc Oxide Nanoparticle on Liver Function, Deposition, and Absorption of Trace Minerals in Intrauterine Growth Retardation Pigs

To investigate the long-term effects of dietary zinc oxide nanoparticle (Nano-ZnO, 20-40 nm) on the relative organ weight, liver function, deposition, and absorption of trace minerals in intrauterine growth retardation (IUGR) pigs, piglets were allocated to NBW (6 normal birth weight piglets fed basal diets), IUGR (6 IUGR piglets fed basal diets) and IUGR+NZ (6 IUGR piglets fed basal diets + 600 mg Zn/kg from Nano-ZnO) groups at weaning (21 days of age), which were sampled at 163 days of age. There were no noteworthy changes in the relative weight of organs, hepatic histomorphology, serum alkaline phosphatase, glutamic pyruvic transaminase and glutamic oxalacetic transaminase activities, and Mn, Cu, and Fe concentrations in leg muscle, the liver, the tibia, and feces among the IUGR, NBW, and IUGR+NZ groups (P > 0.05), and no intact Nano-ZnO in the jejunum, liver, and muscle was observed, while dietary Nano-ZnO increased the Zn concentrations in the tibia, the liver, serum, and feces (P < 0.05) and mRNA expression of metallothionein (MT) 1A, MT2A, solute carrier family 39 member (ZIP) 4, ZIP14, ZIP8, divalent metal transporter 1, solute carrier family 30 member (ZnT) 1, ZnT4 and metal regulatory transcription factor 1, and ZIP8 protein expression in jejunal mucosa (P < 0.05). Immunohistochemistry showed that dietary Nano-ZnO increased the relative optical density of ZIP8 (mainly expressed in cells of brush border) and MT2A (mainly expressed in villus lamina propria and gland/crypt) (P < 0.05). In conclusion, long-term dietary Nano-ZnO showed no obvious side effects on the development of the major organs, liver function, and metabolism of Cu, Fe, and Mn in IUGR pigs, while it increased the Zn absorption and deposition via enhancing the expression of transporters (MT, ZIP, and ZnT families) in the jejunum, rather than via endocytosis as the form of intact nanoparticles.