High Zinc Supplementation Research Articles

High-Zinc Supplementation of Weaned Piglets Affects Frequencies of Virulence and Bacteriocin Associated Genes Among Intestinal Escherichia coli Populations.

To prevent economic losses due to post-weaning diarrhea (PWD) in industrial pig production, zinc (Zn) feed additives have been widely used, especially since awareness has risen that the regular application of antibiotics promotes buildup of antimicrobial resistance in both commensal and pathogenic bacteria. In a previous study on 179 Escherichia coli collected from piglets sacrificed at the end of a Zn feeding trial, including isolates obtained from animals of a high-zinc fed group (HZG) and a corresponding control group (CG), we found that the isolate collection exhibited three different levels of tolerance toward zinc, i.e., the minimal inhibitory concentration (MIC) detected was 128, followed by 256 and 512 μg/ml ZnCl2. We further provided evidence that enhanced zinc tolerance in porcine intestinal E. coli populations is clearly linked to excessive zinc feeding. Here we provide insights about the genomic make-up and phylogenetic background of these 179 E. coli genomes. Bayesian analysis of the population structure (BAPS) revealed a lack of association between the actual zinc tolerance level and a particular phylogenetic E. coli cluster or even branch for both, isolates belonging to the HZG and CG. In addition, detection rates for genes and operons associated with virulence (VAG) and bacteriocins (BAG) were lower in isolates originating from the HZG (41 vs. 65% and 22 vs. 35%, p < 0.001 and p = 0.002, resp.). Strikingly, E. coli harboring genes defining distinct pathotypes associated with intestinal disease, i.e., enterotoxigenic, enteropathogenic, and Shiga toxin-producing E. coli (ETEC, EPEC, and STEC) constituted 1% of the isolates belonging to the HZG but 14% of those from the CG. Notably, these pathotypes were positively associated with enhanced zinc tolerance (512 μg/ml ZnCl2 MIC, p < 0.001). Taken together, zinc excess seems to influence carriage rates of VAGs and BAGs in porcine intestinal E. coli populations, and high-zinc feeding is negatively correlated with enteral pathotype occurrences, which might explain earlier observations concerning the relative increase of Enterobacterales considering the overall intestinal microbiota of piglets during zinc feeding trials while PWD rates have decreased.

The Hepatoprotective Effects of Zinc Glycine on Liver Injury in Meat Duck Through Alleviating Hepatic Lipid Deposition and Inflammation

Dietary zinc status was recently approved to exert a powerful influence on liver health, and zinc deficiency results in hepatic injury caused by fat deposition, inflammation, and oxidant stress, but the effect of zinc on hepatic lipid metabolism and liver injury in meat duck has not been well defined. To determine the hepatoprotective effects of graded zinc glycine in meat ducks. A total of 384 1-day-old male meat ducks were subjected to 5 weeks feeding program with three experimental diets: (1) low-zinc diet, (2) adequate-zinc diet, and (3) high-zinc diet. Blood and liver samples were collected for biochemical analysis, gene expression analysis, and histopathological study. Diet with low zinc increased hepatic lipid content and triglyceride concentration. Meat ducks fed low-zinc diet exhibited considerably increased serum alanine aminotransferase (ALT) activity than birds fed other diets among all groups (P < 0.05). Low zinc administration also notably induced hepatocyte apoptosis and stimulated hepatic inflammatory gene expression. Adequate or high zinc supplementation increased hepatic zinc level, reduced hepatic lipid deposition and hepatosomatic indices through suppressing the expression of lipogenic genes including fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (P < 0.05), and upregulated the mRNA expression of both fatty acid secretion and β-oxidation, including carnitine palmitoyltransferase 1a (Cpt1a), peroxisome proliferator-activated receptor (PPAR)α, and apolipoprotein B (ApoB) (P < 0.05). Dietary zinc addition also declined hepatic mRNA expression of interleukin (IL)-1β and IL-6 (P < 0.05). Furthermore, diets with adequate or high zinc significantly decreased serum ALT activity and hepatocyte apoptosis. These data revealed that supplementing adequate- or high-zinc glycine efficiently protects liver injury by attenuating lipid deposition and hepatic inflammation.

Zinc supplementation increases protein titer of recombinant CHO cells.

In order to study the impact of zinc and copper on the titer levels of mAb and recombinant protein in CHO cells, the IgG-expressing (DP12) and EPO-expressing (SK15) cell lines were cultured in chemically defined media with increasing concentrations of either metal. Supplementation with 25mg/l in CDM media resulted in a significant increase in EPO (1.7-fold) and IgG (2.6-fold) titers compared to control (no added zinc). Titers at this Zn concentration in CDM containing the insulin replacing agent aurintricarboxylic acid (ATA) (CDM + A) showed a 1.8-fold (EPO) and 1.2-fold (IgG) titers increase compared to control. ATA appeared to also reduce the specific productivity (Qp) enhancement induced by Zn-25, with up to 4.9-fold (DP12) and 1.9-fold (SK15) Qp increase in CDM compared to the 1.6-fold (DP12) and 1.5-fold (SK15) Qp increase observed in CDM + A. A 31% reduced Viable Cell Density (VCD) in DP12 was observed in both Zn-supplemented media (3 × 106 cells/ml vs 4.2 × 106 cells/ml, day 5), whereas SK15 Zn-25 cultures displayed a 24% lower peak only in CDM + A (2.2 × 106 cells/ml vs 3.2 × 106 cells/ml, day 5). Supplementation with copper at 13.7-20mg/l resulted in less significant cell line/product-type dependent effects on titer, VCD and Viability. Analysis of the energetic phenotype of both cell lines in 25mg/l Zn-supplemented CDM media revealed a twofold increase in the oxygen consumption rate (OCR) compared to non-supplemented cells. Together, these data suggest that high zinc supplementation may induce an increase in oxidative respiration metabolism that results in increased Qp and titers in suspension CHO cultures.

Zinc treatment is efficient against Escherichia coli \u03b1-haemolysin-induced intestinal leakage in mice

Zinc homoeostasis exerts protective effects in inflammatory intestinal diseases and zinc supplementation has been successfully used for treating infectious diarrhoea. This study aimed at a characterisation of zinc effects on focal leak induction by α-haemolysin (HlyA)-producing Escherichia coli (E. coli) as protective mechanism for colitis. We conducted in vivo experiments by oral challenge of gnotobiotic mice colonised with HlyA-expressing E. coli-536. Mice were either fed a defined normal or high zinc diet to analyse effects of zinc as a therapeutic regimen. HlyA-deficient E. coli-536 mutants were used as controls. Mice infected with HlyA-producing E. coli showed impaired barrier integrity when receiving normal zinc. High zinc supplementation in HlyA-producing E. coli-infected mice reduced epithelial dysfunction as indicated by ameliorated macromolecule permeability. Reduced size of focal leaks with diminished bacterial translocation was observed as inherent mechanisms of this zinc action. In human colon cell monolayers application of zinc rescued the HlyA-dependent decline in transepithelial electrical resistance via reduction of the calcium entry into HlyA-exposed cells. Calcium-dependent cell exfoliation was identified as mechanism for focal leak induction. In conclusion, zinc supplementation protects from HlyA-induced barrier dysfunction in vivo and in vitro, providing an explanation for the protective efficacy of zinc in intestinal disorders.

Microcirculatory effects of zinc on fructose-fed hamsters

Background and aimsFructose is a major dietary component directly related to vascular dysfunction and diseases such as obesity, diabetes, and hypertension. Zinc is considered a non-pharmacological alternative for treating diabetes due to its antioxidant and hyperglycemia-lowering effects in diabetic animals. Therefore, the aim of this study was to evaluate the effects of dietary zinc supplementation on the microcirculatory parameters of fructose-fed hamsters. Methods and ResultsMale hamsters (Mesocricetus auratus) were fed drinking water substituted by 10% fructose solution for 60 days, whereas control animals were fed drinking water alone. Their microcirculatory function was evaluated using cheek pouch preparation, as well as their blood glucose and serum insulin levels. Their microcirculatory responses to acetylcholine (ACh, an endothelium-dependent vasodilator) and to sodium nitroprusside (SNP, an endothelium-independent vasodilator) as well as the increase in macromolecular permeability induced by 30 min of ischemia/reperfusion (I/R) were noted. Endothelium-dependent vasodilation was significantly increased in control animals with high zinc supplementation compared to the groups without zinc supplementation. Zinc was able to protect against plasma leakage induced by I/R in all control and fructose-fed groups, although the microvascular permeability was higher in animals fed drinking water substituted by 10% fructose solution compared to those fed filtered drinking water alone. ConclusionOur results indicate that dietary zinc supplementation can improve microvascular dysfunction by increasing endothelial-dependent dilatation and reducing the increase in macromolecular permeability induced by I/R in fructose-fed animals.

Influence of weaning and effect of post weaning dietary zinc and copper on electrophysiological response to glucose, theophylline and 5-HT in piglet small intestinal mucosa

This study aimed to examine how weaning and how dietary zinc and/or copper fed post weaning may affect the electrophysiological response to glucose and to chloride secretagogues in piglet small intestine in vitro. Study 1 included 54 piglets (six litters of nine piglets). One piglet from every litter was killed 1 day before weaning. The remaining 48 piglets were allocated at weaning (28 d) to four dietary zinc treatments and subsequently killed 1–2, 5–6 or 14–15 days after weaning. Study 2 included 48 piglets (six litters of eight piglets) allocated to four dietary treatments, consisting of high or low dietary zinc with or without high dietary copper. All piglets in study 2 were killed 5–7 days after weaning. The in vitro studies in Ussing chambers showed that weaning resulted in increased ileal glucose absorption as well as increased neuroendocrine-regulated (activated by 5-HT) and cAMP-dependent (activated by theophylline) chloride secretion. High zinc supplementation reduced the responses to 5-HT and theophylline. The study did not reveal any influence of copper on these parameters. It is concluded that the positive effect of zinc supplementation on diarrhoea in weaned piglets may be due to zinc reducing the intestinal mucosal susceptibility to secretagogues that activate chloride secretion.

Effect of zinc on the immune status of zinc-depleted AIDS related complex patients

Zinc deficiency has been recently reported in AIDS patients to be associated with a decrease in T helper cells. The effect of zinc supplementation was evaluated in 5 ARC patients and 5 control subjects using lymphocyte subset counts, blast transformation and chemiluminescence of polymorphonuclear leukocytes. Zinc was analysed by atomic absorption spectrophotometry. T-cell subsets were quantified by cytofluorometry. Chemiluminescence of PMN was measured by phagocytosis of opsonized zymosan. The ARC patients had significantly lower zinc concentrations in the RBC prior to supplementation (p < 0.05). This level increased following the administration of zinc gluconate. This increase was accompanied by (i) an increase in HLA.Dr + cells with no CD4 CD8 ratio alteration; (ii) a stimulation of lymphocyte transformation and PMN chemiluminescence particularly after 15 days' high zinc supplementation. Such a reconstitution in specific and non specific immune functions in ARC patients may warrant further investigation.

High Zinc Supplementation of Rainbow Trout Diets

Abstract Zinc in the form of zinc sulfate or chelated as zinc proteinate was fed in increasing levels (4 to 1,700 µg/g zinc) in an egg-white based diet to fingerling rainbow trout (Salmo gairdneri) to determine potential toxicity. Zinc sulfate was fed for the first 55 days and zinc proteinate for the last 118 days of a 173-day test. Fish fed the lowest level of zinc (4 µg/g zinc, a zinc-deficient diet) had poor growth and high mortalities, while the lowest level of added zinc (90 µg/g) reduced mortalities and markedly improved growth. Higher levels of supplemented zinc, up to 1,700 µg/g, had no further effect on growth or survival. Zinc concentration in liver, blood, and gills increased with dietary levels of zinc above 90 µg/g. Trout showed no signs of zinc toxicity during feeding with levels of dietary zinc as high as 1,700 µg/g.