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.

Effects of Supranutritional Selenium Nanoparticles on Immune and Antioxidant Capacity in Sprague-Dawley Rats.

The present study was conducted to investigate the effects of supranutritional selenium nanoparticles (SeNPs) on immune and antioxidant capacity in rats. Forty male Sprague-Dawley (SD) rats were randomly divided into four groups and given intragastric administration of SeNPs at doses of 0, 0.2, 0.4, and 0.8 mg Se/kg BW, respectively, for 2 weeks. Serum immune parameters, serum and organic tissues (liver, heart, kidney) antioxidant indices, and liver mRNA expression of glutathione peroxidase 1 (GPx1) and glutathione peroxidase 4 (GPx4) were examined. The results showed that supranutritional doses of 0.4 and 0.8 mg Se/kg BW SeNPs promoted the immune responses in serum. SeNPs administration improved antioxidant capacity in the liver and kidney, and the best improvement on antioxidant capacity was found in the kidney. Furthermore, intragastric administration of SeNPs upregulated mRNA expression of GPx1 and GPx4 in the liver. The results obtained indicated that SeNPs administration at supranutritional levels had beneficial effects on immune and antioxidant capacity and supplemental SeNPs at dose of 0.4 mg Se/kg BW exhibited the best response in SD rats.

Prooxidation and Cytotoxicity of Selenium Nanoparticles at Nonlethal Level in Sprague-Dawley Rats and Buffalo Rat Liver Cells.

The effects of selenium nanoparticles (SeNPs) on the antioxidant capacity in Sprague-Dawley (SD) rats were investigated. The rats were given intragastric administration of an SeNP suspension at doses of 0, 2, 4, and 8 mg Se/kg BW for two weeks. The antioxidant capacity in serum and organic tissues (liver, heart, and kidney) and the gene expression levels of glutathione peroxidase 1 (GPX1) and glutathione peroxidase 4 (GPX4) in the liver were measured. Buffalo rat liver (BRL) cell lines were further constructed to explore the cytotoxicity mechanism induced by SeNPs through the determination of antioxidant capacity; cell activity; apoptosis; and Caspase-3, Caspase-8, and Caspase-9 family activities. The results showed that SeNP administration over 4.0 mg Se/kg BW decreased the antioxidant capacities in the serum, liver, and heart and downregulated mRNA expression of GPX1 and GPX4 in the liver. The BRL cell line experiments showed that treatment with over 24 µM SeNPs decreased the viability of the cells and damaged the antioxidant capacity. Flow cytometry analysis showed that decreased cell viability induced by SeNPs is mainly due to apoptosis, rather than cell necrosis. Caspase-3 and Caspase-8 activities were also increased when BRL cells were treated with 24 µM and 48 µM SeNPs. Taken together, a nonlethal level of SeNPs could impair the antioxidant capacity in serum and organic tissues of rats, and the liver is the most sensitive to the toxicity of SeNPs. A pharmacological dose of SeNPs could lead to cytotoxicity and induce cell death through apoptosis and extrinsic pathways contributing to SeNP-induced apoptosis in BRL cells.

Effects of Selenium Nanoparticles on Reproductive Performance of Male Sprague-Dawley Rats at Supranutritional and Nonlethal Levels.

This research investigated the influence of selenium nanoparticles (SeNPs) on the reproductive performance of male Sprague-Dawley (SD) rats. A suspension of SeNPs was consecutively administered by oral gavage for 2 weeks at supranutritional (0.2, 0.4, or 0.8 mg Se/kg bw) and nonlethal (2.0, 4.0, or 8.0 mg Se/kg bw) levels to male SD rats. The normal control (NC) rats were exposed to physiological saline alone. Biochemical parameters, sperm motility, gene expression of GPx1 and GPx4, and histopathological evaluation of male spermary were measured in this work. The supranutritional doses could promote the sperm motility (P < 0.001) and movement parameters (P < 0.05). The nonlethal levels of 4.0 and 8.0 mg Se/kg bw reduced the testis weight (P < 0.001), sperm concentration, and motility (P < 0.05), and also caused histopathological injury of testis and epididymis tissues to various degrees. The content of testosterone in serum was increased in the 0.8 group (P < 0.05) and decreased in the 4.0 (P < 0.01) and 8.0 mg Se/kg bw groups (P < 0.001), respectively. No significant effects were observed on antioxidant enzyme activities and mRNA concentration of GPx in the supranutritional dose group, and nonlethal levels were also not observed. In conclusion, SeNPs in the supranutritional dose has a positive effect on the reproductive function of male SD rats and has damaging effect higher than 4.0 mg Se/kg bw.

Effects of Chromium-Loaded Chitosan Nanoparticles on Glucose Transporter 4, Relevant mRNA, and Proteins of Phosphatidylinositol 3-Kinase, Akt2-Kinase, and AMP-Activated Protein Kinase of Skeletal Muscles in Finishing Pigs.

The study was conducted to evaluate the effects of chromium-loaded chitosan nanoparticles (Cr-CNP) on glucose transporter 4 (GLUT4), relevant messenger RNA (mRNA), and proteins involved in phosphatidylinositol 3-kinase (PI3K), Akt2-kinase, and AMP-activated protein kinase (AMPK) of skeletal muscles in finishing pigs. A total of 120 crossbred barrows (BW 65.00 ± 1.26 kg) were randomly allotted to four dietary treatments, with three pens per treatment and 10 pigs per pen. Pigs were fed the basal diet supplemented with 0, 100, 200, or 400 µg/kg of Cr from Cr-CNP for 35 days. After the feeding trials, 24 pigs were slaughtered to collect longissimus muscle samples for analysis. Cr-CNP supplementation increased GLUT4 messenger RNA (mRNA) (quadratically, P < 0.01) and total and plasma membrane GLUT4 protein contents (linearly and quadratically, P < 0.001) in skeletal muscles. Glycogen synthase kinase 3ß (GSK-3ß) mRNA was decreased linearly (P < 0.001) and quadratically (P < 0.001). Supplemental Cr-CNP increased insulin receptor (InsR) mRNA quadratically (P < 0.01), Akt2 total protein level linearly (P < 0.01) and quadratically (P < 0.001), and PI3K total protein was increased significantly (P < 0.05) in 200 µg/kg treatment group. The mRNA of AMPK subunit gamma-3 (PRKAG3) and protein of AMPKα1 was significantly increased (P < 0.001) with the addition of Cr-CNP. The results indicate that dietary supplementation of Cr-CNP may promote glucose uptake by leading to recruitment of GLUT4 to the plasma membrane in skeletal muscles, and these actions may be associated with the insulin signal transduction and AMPK.

Toxicity of selenium nanoparticles in male Sprague-Dawley rats at supranutritional and nonlethal levels.

AIMS: We synthesized selenium nanoparticles (SeNPs) and examined their toxicity in male rats at supranutritional and nonlethal doses. MAIN METHODS: The SeNPs were administered daily by gavage at doses of 0.0, 0.2, 0.4, 0.8, 2.0, 4.0, or 8.0 mg Se/kg-body weight (bw) in 2 mL of 0.9% saline for 14 consecutive days. Body weight, viscera index and blood biochemical parameters were measured. Histopathological examination was performed on selected tissues, and liver tissue was examined for apoptotic cells. KEY FINDINGS: Body weight decreased considerably in the groups given doses of 2.0, 4.0, and 8.0 mg Se/kg-bw, but increased in the groups given doses of 0.2 and 0.4 mg Se/kg-bw. The viscera index and some biochemical parameters in the 8.0 mg Se/kg-bw group differed from the control group. Lesions in the liver, kidneys, lungs, and thymus, and apoptotic liver cells were observed in the 4.0 and 8.0 mg Se/kg-bw groups. SIGNIFICANCE: From this study, we conclude that supranutritional levels of SeNPs had no obvious toxic effects in rats, and could be used as potential candidates for cancer chemoprevention, although doses greater than 2.0 mg Se/kg-bw induced chronic toxicity.

Effects of chromium-loaded chitosan nanoparticles on growth, blood metabolites, immune traits and tissue chromium in finishing pigs.

Effects of chromium-loaded chitosan nanoparticles (Cr-CNP) on growth performance, blood metabolites, immune traits, and tissue chromium in finishing pigs were investigated. A total of 160 crossbred barrows (66.06 ± 1.01 kg initial weight) were randomly divided into four groups, each group with four pens, ten pigs per pen. Pigs were fed on the same basal diet supplemented with 0 (the control), 100, 200, and 400 µg/kg Cr from Cr-CNP. All pigs were given free access to feed and water. Eight pigs from each treatment were selected to collect blood and tissue samples after 35 days on trial for analysis of blood metabolites and immune traits and tissue chromium. The results of feeding trial showed that there were no significant difference in growth performance between control and Cr-CNP-treated groups. The supplementation of Cr-CNP decreased serum glucose (P < 0.001) in a linear and quadratic manner. Serum immunoglobulins A and M were linearly increased in Cr-CNP-treated groups (P < 0.001), and serum complement 4 in Cr-CNP-treated groups was also linearly increased (P < 0.05). Cr-CNP supplementation linearly increased the chromium content in the blood, longissimus muscle, heart, liver, kidney, and pancreas (P < 0.001). These results suggested that dietary supplementation of Cr as Cr-CNP affects serum glucose, influences immune status, and increases the tissue chromium content of blood, muscle, and selected organs in finishing pigs.

Effects of copper-loaded chitosan nanoparticles on intestinal microflora and morphology in weaned piglets.

The objective of the present study was to investigate the effects of dietary supplementation with copper-loaded chitosan nanoparticles (CNP-Cu) on growth performance, intestinal microflora, and morphology in weaned piglets. A number of 90 weaned piglets (Duroc × Landrace × Yorkshire), weaned at 21 days with body weight of 7.2 ± 0.81 kg, were randomly divided into three groups by weight and sex, each treatment including three replicates of ten pigs. The piglets were fed the same basal diet supplemented with 0 (the control group), 100 mg/kg CNP-Cu, and 100 mg/kg chlortetracycline (the positive group). The results showed that 100 mg/kg CNP-Cu significantly increased average daily gain and feed intake and decreased feed/gain ratio and diarrhea rate (P < 0.05). Compared with the control group, the amount of Escherichia coli in duodenum, jejunal, and caecum were significantly decreased by 100 mg/kg CNP-Cu; the number of lactobacillus in jejunal and caecum were increased (P < 0.05), and the amount of bifidobacterium in duodenum and caecum were also increased (P < 0.05). Moreover, the villous height of duodenum, jejunum, and ileum mucosa was significantly increased (P < 0.05), and the crypt depth was significantly decreased (P < 0.05). The results indicated that CNP-Cu is beneficial to growth and intestinal microflora and morphology and could be a potential substitution of chlortetracycline in diets of weaned piglets.

Efficacy of dietary chromium (III) supplementation on tissue chromium deposition in finishing pigs.

The study was conducted to evaluate the efficacy of different forms of trivalent chromium (Cr) supplementation on tissue chromium deposition in finishing pigs. A total of 96 pigs with an initial average body mass 65.57±1.05 kg were blocked by body mass and randomly assigned to four treatments with three replicates. Pigs were offered one of four diets including a control diet or the control diet supplemented with 200 µg/kg chromium from either chromium chloride (CrCl(3)), chromium picolinate (CrPic) or chromium nanocomposite (CrNano) for 40 days. During the trial, all pigs were given free access to feed and water. After feeding trial, eight pigs from each treatment were slaughtered for samples collection. The results showed that supplemental CrNano increased Cr content in blood, longissimus muscle, heart, liver, kidney, jejunum, and ileum (P<0.05). Supplemental Cr from three sources increased Cr excretion from all feces (P<0.05). Urinary Cr excretion was increased by CrNano or CrPic supplementation significantly. These results suggested that chromium nanocomposite exhibited more effective on tissue Cr deposition in pigs, which indicated higher absorption compared with CrCl(3) and CrPic.