title: 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.
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Feed Science, College of Animal Science, Zhejiang University, Key Laboratory of Molecular Animal Nutrition, Ministry of Education, Hangzhou Zhejiang Province, People's Republic of China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Lu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Le
authors.initials: L
authors.lastname: Zhou
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Jiaman
authors.initials: J
authors.lastname: Xu
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Weijian
authors.initials: W
authors.lastname: Li
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhong
authors.affiliation: College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, People's Republic of China.
authors.forename: Tian
authors.initials: T
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003300:Copper / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007501:Iron / Q000378:metabolism; D007583:Jejunum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008345:Manganese / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008903:Minerals / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity / Q000648:ultrastructure; D009929:Organ Size / Q000187:drug effects; D015032:Zinc / Q000378:metabolism; D015034:Zinc Oxide / Q000008:administration & dosage / Q000378:metabolism* / Q000633:toxicity
chemical_list: D008903:Minerals; D008345:Manganese; D003300:Copper; D007501:Iron; D015032:Zinc; D015034:Zinc Oxide