Hepatic Zinc Research Articles

Normalization of Fetal Cerebral and Hepatic Iron by Parental Iron Therapy to Pregnant Rats with Systemic Iron Deficiency without Anemia.

Iron (Fe) is a co-factor for enzymes of the developing brain necessitating sufficient supply. We investigated the effects of administering ferric derisomaltose/Fe isomaltoside (FDI) subcutaneously to Fe-deficient (ID) pregnant rats on cerebral and hepatic concentrations of essential metals and the expression of iron-relevant genes. Pregnant rats subjected to ID were injected with FDI on the day of mating (E0), 14 days into pregnancy (E14), or the day of birth (postnatal (P0)). The efficacy was evaluated by determination of cerebral and hepatic Fe, copper (Cu), and zinc (Zn) and gene expression of ferroportin, hepcidin, and ferritin H + L in pups on P0 and as adults on P70. Females fed an ID diet (5.2 mg/kg Fe) had offspring with significantly lower cerebral and hepatic Fe compared to female controls fed a standard diet (158 mg/kg Fe). Cerebral Cu increased irrespective of supplying a standard diet or administering FDI combined with the standard diet. Hepatic hepcidin mRNA was significantly lower following ID. Cerebral hepcidin mRNA was hardly detectable irrespective of iron status. In conclusion, administering FDI subcutaneously to ID pregnant rats on E0 normalizes fetal cerebral and hepatic Fe. When applied at later gestational ages, supplementation with additional Fe to the offspring is needed to normalize cerebral and hepatic Fe.

Hepatic ZBTB22-mediated detoxification ameliorates acetaminophen-induced liver injury by inhibiting pregnane X receptor signaling

Overdose acetaminophen (APAP) can cause acute liver injury (ALI), but the underlying mechanism remains undetermined. This study explored the role of hepatic Zinc Finger And BTB Domain Containing 22 (ZBTB22) in defense against APAP-mediated hepatotoxicity. The results showed that hepatic ZBTB22 expression was significantly reduced in patients with ALI and mice. In mouse primary hepatocytes (MPHs), ZBTB22 deletion aggravated APAP overdose-induced ALI, whereas ZBTB22 overexpression attenuated that pathological progression. The results were further verified in ZBTB22 over-express or knockout mice models. In parallel, hepatocyte-specific ZBTB22 knockout also enhanced ALI. Furthermore, ZBTB22 decreased pregnane X receptor (PXR) expression, and the PXR activator pregnane-16α-carbonitrile suppressed the protective effect of ZBTB22 in APAP-induced ZBTB22-overexpressing mice. Collectively, our findings highlight the protective effect of ZBTB22 against APAP-induced ALI and unravel PXR signaling as the potential mechanism. Strategies to increase hepatic ZBTB22 expression represent a promising therapeutic approach for APAP overdose-induced ALI.

Metallothionein I and II Protect against Zinc Deficiency and Zinc Toxicity in Mice

Metallothionein (MT)-bound zinc accumulates when animals are exposed to excess zinc and is depleted under conditions of zinc deficiency, suggesting that MT serves as a means of sequestering excess zinc as well as a zinc reservoir that can be utilized when zinc is deficient. To examine the importance of MT for these processes, mice with null alleles of both MT I and MT II genes were created and the zinc concentration and histological appearance of multiple organs assessed. At birth, the hepatic zinc concentration of these MT-null mice was lower than that of wild-type controls (0.27 ± 0.02 vs. 0.65 ± 0.11 µmol zinc/g tissue, P < 0.05). During the next 3 wk of suckling zinc-replete (95 µg zinc/g diet) dams, the hepatic zinc concentration of controls fell to 0.42 ± 0.04 µmol/g but was unchanged in the MT-null mice (0.28 ± 0.04 µmol/g). The most prominent histological anomaly observed at 3 wk of age was the presence of swollen Bowman's capsules in the kidneys of MT-null mice. When nursing MT-null dams were fed a severely zinc-deficient (1.5 µg/g) diet, kidney development in the MT-null pups was retarded as indicated by the retention of the nephrogenic zone and incomplete tubule development. We suggest that the lack of a hepatic reservoir of zinc jeopardizes the developing kidney in the MT-null mice. In addition to being more sensitive to dietary zinc restriction, MT-null mice are more sensitive to zinc toxicity. When adult mice were challenged with a ramping dose of zinc up to a total of 3700 µmol zinc/kg body weight, MT-null mice had a greater incidence of pancreatic acinar cell degeneration compared with control mice despite accumulating less zinc (2.72 ± 0.46 vs. 1.23 ± 0.52 µmol zinc/g pancreas, control and MT-null, respectively, P < 0.05). The results of these experiments suggest that MT I and MT II can protect against both zinc deficiency and zinc toxicity.

MCD Diet Rat Model Induces Alterations in Zinc and Iron during NAFLD Progression from Steatosis to Steatohepatitis.

We evaluate the effects of the methionine-choline-deficient (MCD) diet on serum and hepatic zinc (Zn) and iron (Fe) and their relationships with matrix metalloproteinases (MMPs) and their modulators (TIMPs and RECK) as well as hepatic fatty acids using male Wistar rats fed 2-, 4- and 8-week MCD diets. Serum and hepatic Zn decrease after an 8-week MCD diet. Serum Fe increases after an 8-week MCD diet and the same occurs for hepatic Fe. An increase in hepatic MMP activity, associated with a decrease in RECK and TIMPs, is found in the MCD 8-week group. Liver Fe shows a positive correlation versus MMPs and RECK, and an inverse correlation versus TIMPs. A positive correlation is found comparing liver Zn with stearic, vaccenic and arachidonic acids, and an inverse correlation is found with linolenic and docosatetraenoic acids. An opposite trend is found between liver Fe versus these fatty acids. During NAFLD progression from steatosis to steatohepatitis, MCD rats exhibit an increase in Zn and a decrease in Fe levels both in serum and tissue associated with alterations in hepatic MMPs and their inhibitors, and fatty acids. The correlations detected between Zn and Fe versus extracellular matrix modulators and fatty acids support their potential role as therapeutic targets.

Gestational Cd Exposure in the CD-1 Mouse Sex-Specifically Disrupts Essential Metal Ion Homeostasis.

In CD-1 mice, gestational-only exposure to cadmium (Cd) causes female-specific hepatic insulin resistance, metabolic disruption, and obesity. To evaluate whether sex differences in uptake and changes in essential metal concentrations contribute to metabolic outcomes, placental and liver Cd and essential metal concentrations were quantified in male and female offspring perinatally exposed to 500 ppb CdCl2. Exposure resulted in increased maternal liver Cd+2 concentrations (364 µg/kg) similar to concentrations found in non-occupationally exposed human liver. At gestational day (GD) 18, placental Cd and manganese concentrations were significantly increased in exposed males and females, and zinc was significantly decreased in females. Placental efficiency was significantly decreased in GD18-exposed males. Increases in hepatic Cd concentrations and a transient prenatal increase in zinc were observed in exposed female liver. Fetal and adult liver iron concentrations were decreased in both sexes, and decreases in hepatic zinc, iron, and manganese were observed in exposed females. Analysis of GD18 placental and liver metallothionein mRNA expression revealed significant Cd-induced upregulation of placental metallothionein in both sexes, and a significant decrease in fetal hepatic metallothionein in exposed females. In placenta, expression of metal ion transporters responsible for metal ion uptake was increased in exposed females. In liver of exposed adult female offspring, expression of the divalent cation importer (Slc39a14/Zip14) decreased, whereas expression of the primary exporter (Slc30a10/ZnT10) increased. These findings demonstrate that Cd can preferentially cross the female placenta, accumulate in the liver, and cause lifelong dysregulation of metal ion concentrations associated with metabolic disruption.

Copper and Zinc Levels in the Liver Tissue of Healthy Cattle Affected by Fasciola hepatica in a Slaughterhouse

Fasciolosis is considered the most important liver disease in animals, the most notorious damages are caused by death, it causes a reduction in the production of meat, wool and milk, seizure of affected organs, secondary infections by bacteria, interference with fertility and expenses derived from its treatment. The objective of this research was to determine the relationship of Cu and Zn levels in the liver with the affectation by Fasciola hepatica in slaughterhouse cattle. Determinations of Cu, Zn, ash and dry matter were carried out using the atomic absorption spectrophotometry technique in healthy liver tissue affected by fasciolosis in 40 cattle slaughtered in the slaughterhouse. The association between possible risk factors for hepatic Cu and Zn values below the critical limit and the event of livers affected by F. hepatica was carried out in a retrospective case-control observational study. The levels of Cu and Zn in healthy livers affected by F. hepatica in cattle slaughtered in the municipal slaughterhouse of Sagua la Grande, Villa Clara, Cuba are deficient and show low reserves of these microelements with values below the critical value. No association was found between Cu and Zn levels in liver tissue with liver involvement by F. hepatica in slaughterhouse cattle, although it was observed that slaughtered cattle with hepatic Zinc values lower than the critical limit are affected approximately two times more due to fasciolosis than bovines with normal hepatic zinc values.

The role of dietary chromium supplementation in relieving heat stress of juvenile blunt snout bream Megalobrama amblycephala

The present study assessed the role of dietary chromium (Cr) supplementation in relieving heat stress (HS) of juvenile blunt snout bream Megalobrama amblycephala. The supplemented Cr contents by chromium picolinate (Cr-Pic) was 0 mg/kg (control group), 0.4 mg/kg, 1.6 mg/kg and 12.0 mg/kg, respectively. The fish continued to be fed four diets at suitable temperatures (26 °C) for 2 weeks, and then the temperature was then heated up to 33 °C through thermo-regulated system. The results showed that Cr supplementation had no significant effect on the immune indices and antioxidant indices before HS (P > 0.05). However, Cr supplementation played an important role in relieving HS. After HS, compared with the control group, 1.6 mg/kg and 12.0 mg/kg Cr supplementation groups significantly lowered the plasma glucose level and aspartate transaminase (AST) activity (P < 0.05), and 0.4 mg/kg and 1.6 mg/kg Cr supplementation groups significantly lowered alanine aminotransferase (ALT) activity (P < 0.05). 0.4 mg/kg and 1.6 mg/kg supplementation groups significantly improved hepatic total superoxide dismutase (T-SOD) activity (P < 0.05). Furthermore, 0.4mg/kg-12.0 mg/kg Cr supplementation groups significantly improved the activities of hepatic glutathione peroxidase (GPx) and catalase (CAT) and lowered hepatic malondialdehyde (MDA) level in liver (P < 0.05). The mRNA levels of hepatic copper zinc superoxide dismutase (Cu/Zn-SOD), CAT and GPx were significantly improved in 0.4mg/kg-12.0 mg/kg supplementation Cr groups (P < 0.05), however, there was no significant variation of hepatic manganese superoxide dismutase (Mn-SOD) mRNA levels under different levels of supplementation (P > 0.05). Significantly lower mRNA levels of hepatic pro-inflammatory cytokines observed in 0.4mg/kg-12.0 mg/kg Cr supplementation groups including tumour necrosis factor-α (TNF-α), interleukin 1β (IL-1β) and interleukin 8 (IL-8) (P < 0.05), and 0.4mg/kg-12.0 mg/kg Cr supplementation significantly improved the relative expressions of hepatic heat shock protein 70 (HSP70) and heat shock protein 90 (HSP90) (P < 0.05). The present study indicated that dietary Cr supplementation might have no significant effect on immune capacity and antioxidant capacity under normal physiological conditions, whereas it played an important role in relieving HS.

ZnT8 Deficiency Protects From APAP-Induced Acute Liver Injury by Reducing Oxidative Stress Through Upregulating Hepatic Zinc and Metallothioneins.

Zinc transporter 8 (ZnT8) is an important zinc transporter highly expressed in pancreatic islets. Deficiency of ZnT8 leads to a marked decrease in islet zinc, which is thought to prevent liver diseases associated with oxidative stress. Herein, we aimed to investigate whether loss of islet zinc affects the antioxidant capacity of the liver and acute drug-induced liver injury. To address this question, we treated ZnT8 knockout (KO) or wild-type control mice with 300 mg/ kg acetaminophen (APAP) or phosphate-buffered saline (PBS). Unexpectedly, we found that loss of ZnT8 in mice ameliorated APAP-induced injury and was accompanied by inhibition of c-Jun N-terminal kinase (JNK) activation, reduced hepatocyte death, and decreased serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). An increase in hepatic glutathione (GSH) was observed, corresponding to a decrease in malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE) levels. APAP-induced inflammation and glycogen depletion were alleviated. In contrast, no significant changes were observed in cytochrome P450 family 2 subfamily E member 1 (CYP2E1), the main enzyme responsible for drug metabolism. Elevated levels of hepatic zinc and metallothionein (MT) were also observed, which may contribute to the hepatoprotective effect in ZnT8 KO mice. Taken together, these results suggest that ZnT8 deficiency protects the liver from APAP toxicity by attenuating oxidative stress and promoting hepatocyte proliferation. This study provides new insights into the functions of ZnT8 and zinc as key mediators linking pancreatic and hepatic functions.

Zinc oxide nanoparticles improve gut health and reduce faecal zinc excretion in piglets

This study investigated the effects of zinc oxide nanoparticles (ZnON) on growth performance, gut health, and zinc and copper excretion in piglets. A total of 144 piglets (Duroc × Landrace × Large White, weaned at 21 days; mean initial weight 6.15 ± 0.01 kg) were assigned to six groups with six replicates of four pigs per pen for a 26-day feeding trial. The groups were: antibiotic group (basal diet + 75 mg/kg aureomycin), ZnO group (basal diet + 1,600 mg/kg zinc oxide), and four ZnON groups (basal diet + 200, 300, 400, or 500 mg/kg ZnON, respectively). No significant difference in growth performance was observed amongst the treatments. ZnON supplementation improved the activities of superoxide dismutase (linear or quadratic, p < 0.05), copper-zinc superoxide dismutase in the ileum (linear, p < 0.05), catalase in the jejunum and ileum (linear or quadratic, p < 0.05), total antioxidant capacity of duodenum and ileum (linear, p < 0.05), and glutathione peroxidase in the ileum (linear, p < 0.05), and reduced malondialdehyde content in the jejunum (linear, p < 0.05). As ZnON content was increased, the contents of jejunal IgA, interleukin (IL)-6, and IL-10 decreased (linear, p < 0.05), while IgM content increased (linear, p < 0.05). The contents of ileal IgA and IL-10 increased (linear and quadratic, p < 0.05), while the contents of IgM, IgG, and IL-6 decreased (linear or quadratic, p < 0.05). Villus height and the ratio of villus height to crypt depth in piglets fed with ZnON were higher than in the antibiotic group (p < 0.05). Pigs fed with 200–500 mg/kg ZnON showed lower contents of hepatic zinc and copper and faecal zinc than the ZnO group (p < 0.05). These results show that dietary ZnON enhanced intestinal antioxidant and immune capacity and intestinal morphology, particularly 500 mg/kg ZnON, and also that ZnON minimised zinc content in the liver and faeces.

Curcumin Reduces Hepatic and White Adipose Tissue Inflammation and Expression of Specific Zinc Transporters in Diet-Induced Obese Mice

Abstract Objectives Obesity is a complex metabolic disease, that is often associated with non-alcoholic fatty liver disease (NAFLD). Inflammation is a common feature of both diseases. Curcumin, a traditionally used spice in Asia, exerts anti-inflammatory effects in liver and white adipose tissue (WAT) of diet-induced obese (DIO) mice. However, mechanisms involved in these beneficial effects remain obscure. Zinc is an important micronutrient involved in inflammatory responses. Whole-body zinc homeostasis plays a critical role in decreasing tissue specific inflammation. Zinc homeostasis is maintained mainly by zinc transporters known as ZnT (zinc transporters) and Zip (Zrt and Irt-like proteins) family. We propose that zinc transporters may contribute to curcumin's protective metabolic effects. Thus, the objective of this research was to determine curcumin's effects on inflammatory markers and zinc transporters in liver and WAT from DIO mice. Methods Male B6 mice were fed a HFD (45% kcal fat) or HFD supplemented with 0.4% (w/w) curcumin (HFC) for fourteen weeks. Serum triglycerides (TG) and free fatty acid (FFA) levels were measured. mRNA levels for inflammatory markers and zinc transporters were determined in WAT and liver by qRT-PCR. Results No significant changes were observed in body weight, serum TG and FFA levels with curcumin supplementation. However, gene expression of inflammatory markers, including Stat1, and Nf-KB subunit p65 were significantly reduced in liver and WAT from HFC group compared to HF (P &amp;lt; 0.05). Furthermore, curcumin reduced hepatic zinc transporters Zip10, Zip14, ZnT10 but increased ZnT9 expression. In WAT, curcumin significantly reduced mRNA levels for Zip1, Zip14, ZnT1, and ZnT7 (P &amp;lt; 0.05). Conclusions Our results indicate that zinc transporters may in part mediate the anti-inflammatory properties of curcumin, particularly Zip14, in WAT and liver of DIO mice. Future mechanistic studies are necessary to establish whether zinc transporters are required for curcumin's anti-inflammatory effects in obesity and associated NAFLD. Funding Sources AHA grant# 19AIREA34450279.

CHANGES IN BLOOD PARAMETERS IN BREEDER TOMS FOLLOWING SUBCUTANEOUS INJECTION WITH CADMIUM

Alterations in blood biochemical values of Yearling breeder toms following parenteral administration of cadmium (Cd) were well evaluated. Each treated member of a pair of (total 24 pairs) 0f toms received a single dose of 4.5mg of Cd per kg. body weight (0.04-mole). The birds were sacrificed at 0,6,24 and 192 hours : post-treatment. Highly significant (P&lt;0.0001).increase in serum Cd concentration was observed in the Cd-injected toms, Reduction in the blood have been used to produce useful serum Cd (P&lt;0.05) at the successive post-necropsy periods indicated systematic clearance of the metal from the fluid. Nearly 50 percent eliminated by 24 h post-treatment. Serum changes glutamic pyruvic transaminase (SGPT) was due to the similarly increased (P&lt;0.05) in the Cd-treated birds and was presumed to have originated mainly from damaged skeletal muscle tissues. The cadmium treatment did not affect (P&gt;0.05) serum testosterone level, total protein, total haemoglobin, lactate dehydrogenase, packed cell volume or serum glutamic oxaloacetic transaminase. It was concluded from these observations that the Cd treatment did not seem to have interfered seriously with renal or hepatic functions, iron, copper and zinc metabolism or caused significant damage to myocardial issue.

Effect of Korean pine nut oil on hepatic iron, copper, and zinc status and expression of genes and proteins related to iron absorption in diet-induced obese mice

Effect of Korean pine nut oil on hepatic iron, copper, and zinc status and expression of genes and proteins related to iron absorption in diet-induced obese mice

Zinc dyshomeostasis in azoxymethane-induced colonic precancerous and cancerous lesions in Fischer rats.

Zinc is an essential micronutrient involved in various biological processes. It is also argued that tumors need zinc for maintenance and proliferation and tumor cell apoptosis. Zinc homeostasis is regulated by the gastrointestinal tract and involves interplay of host, dietary, environmental and social factors such as alcohol consumption. The DNA alkylation agent azoxymethane (AOM), which is primarily activated in the liver, induces a high incidence of initiation and promotion steps of precancerous lesions in the colon of rats. The altered expression of hepatic zinc transporters by AOM may lead to zinc dyshomeostasis in liver. Decreased serum zinc concentration, despite increased liver zinc also indicates altered liver zinc mobilization and failure to regulate zinc homeostasis. During the transformation from normal colonic mucosa to colonic epithelial hyperplasia and aberrant crypt formation, a reduction in zinc concentration is observed. It will be interesting to study further if the same trend continues throughout tumor progression towards adenocarcinomas. Lowered local zinc concentrations in the colon epithelium may not just reflect a bystander effect, but may induce cell proliferation and compromise DNA integrity due to impairment of zinc-containing proteins. In congruence with the tissue zinc concentrations, metallothionein levels were found to be less induced in AOM -administered colon compared to normal healthy colon. Lowered tissue zinc levels in small and large intestine were also associated with increased expression of mRNA and protein ZnT1. In this regard, the mode of zinc responsiveness to ZnT1 mimics that of metallothionein, albeit at a lower level for ZnT1.

PSIV-21 Time course and peak response of inflammation and tissue zinc transporters during LPS-induced sepsis in nursery pigs fed pharmacological levels of dietary zinc and copper

Abstract This study evaluated the effects of lipopolysaccharide (LPS) injection on the immune response over a 24-h period in nursery pigs. Pigs consumed corn-soybean meal-based diets with added pharmacological levels of ZnO (d 0–14) and CuSO4 (d 14–23). On d 23, thirty pigs were randomly blocked based on BW and sex to one of five-time points (h 0 baseline, 3, 6, 12, and 24 post-challenge) and injected with a single i.m. LPS (O55:B5) at 12 μg/kg BW. At each time point, BW, rectal temperature (RT), and blood samples (n = 30, 24, 18, 12, and 6 per time point, respectively) were collected before one block (n = 6) was euthanized for liver and duodenum collection. Tissue samples were quantified for interleukin-6 (IL-6), zinc transporters (duodenal Zip4 and hepatic Zip14), and metallothionein-1 (MT-1) mRNA expression. Data were analyzed using PROC GLIMMIX of SAS with pig as the experimental unit. Following LPS, RT increased from h 0 to 6 (P &amp;lt; 0.05), and serum TNF-α increased from h 0 to 3 (P &amp;lt; 0.0001). Serum zinc and copper decreased (P &amp;lt; 0.01) from h 0 to 6, and h 0 to 12, respectively. Serum C-reactive protein tended to increase linearly following LPS (P = 0.10). LPS upregulated duodenal Zip4 and MT-1 (P &amp;lt; 0.05) at h 12 and 24, respectively, while all hepatic genes increased (P &amp;lt; 0.01) at h 3 post-challenge. Duodenal IL-6 did not change over time (P &amp;gt; 0.05). Quantification of mRNA expression displayed a positive correlation (P &amp;lt; 0.01) among hepatic IL-6, Zip14, and MT-1 in pairwise comparisons. In summary, LPS challenge induces fever and hepatic inflammation with consequent increases in hepatic and duodenal zinc importers, and their metal-binding protein, along with decreases in serum zinc and copper concentrations. However, our data indicate that pigs recover within 24-hour post-challenge.

Alterations in the Intestinal Morphology, Gut Microbiota, and Trace Mineral Status Following Intra-Amniotic Administration (Gallus gallus) of Teff (Eragrostis tef) Seed Extracts.

The consumption of teff (Eragrostis tef), a gluten-free cereal grain, has increased due to its dense nutrient composition including complex carbohydrates, unsaturated fatty acids, trace minerals (especially Fe), and phytochemicals. This study utilized the clinically-validated Gallus gallus intra amniotic feeding model to assess the effects of intra-amniotic administration of teff extracts versus controls using seven groups: (1) non-injected; (2) 18Ω H2O injected; (3) 5% inulin; (4) teff extract 1%; (5) teff extract 2.5%; (6) teff extract 5%; and (7) teff extract 7.5%. The treatment groups were compared to each other and to controls. Our data demonstrated a significant improvement in hepatic iron (Fe) and zinc (Zn) concentration and LA:DGLA ratio without concomitant serum concentration changes, up-regulation of various Fe and Zn brush border membrane proteins, and beneficial morphological changes to duodenal villi and goblet cells. No significant taxonomic alterations were observed using 16S rRNA sequencing of the cecal microbiota. Several important bacterial metabolic pathways were differentially enriched in the teff group, likely due to teff’s high relative fiber concentration, demonstrating an important bacterial-host interaction that contributed to improvements in the physiological status of Fe and Zn. Therefore, teff appeared to represent a promising staple food crop and should be further evaluated.

Effect of the Source of Zinc on the Tissue Accumulation of Zinc and Jejunal Mucosal Zinc Transporter Expression in Holstein Dairy Calves.

Simple SummaryDiarrhea is the main cause of death in newborn calves and is associated with antibiotic use and economic loss for dairy farms. In this study, we evaluated the effects of different sources of the mineral zinc (zinc oxide (ZnO) and zinc methionine (Zn-Met)) on the growth, incidence of diarrhea, tissue zinc accumulation, gene expression of jejunal zinc transporters and serum concentrations of zinc-dependent proteins in newborn Holstein dairy calves. We found that Zn-Met supplementation promoted growth and reduced diarrhea from the second week after birth. It also increased the levels of zinc in the serum and liver, the level of the transporter protein ZIP4 in the jejunal mucosa, as well as the serum alkaline phosphatase and metallothionein concentrations compared to the control group. ZnO supplementation had similar but less marked effects to Zn-Met supplementation. These results suggest that Zn-Met supplementation may be an alternative to antibiotics for the treatment of newborn calf diarrhea.Zinc is considered to be an anti-diarrheal agent, and it may therefore reduce the incidence of diarrhea in young calves. In the present study, we aimed to compare the effect of zinc source on growth performance, the incidence of diarrhea, tissue zinc accumulation, the expression of zinc transporters, and the serum concentrations of zinc-dependent proteins in neonatal Holstein dairy calves. Eighteen male newborn Holstein dairy calves were fed milk and starter diet supplemented with or without 80 mg zinc/d in the form of Zn-Met or ZnO for 14 days, and were then euthanized. Zn-Met supplementation improved average daily gain and feed efficiency, and reduced the incidence of diarrhea, compared with control calves (p < 0.05). It also increased the serum and hepatic zinc concentrations and the mRNA expression of the ZIP4 transporter in the jejunal mucosa of the calves (p < 0.05). In addition, the serum alkaline phosphatase activity and metallothionein concentration were higher in Zn-Met-treated calves than in control calves (p < 0.05). ZnO supplementation had similar effects, but these did not reach significance. Thus, Zn-Met supplementation is an effective means of increasing tissue zinc accumulation and jejunal zinc absorption, and can be used as an anti-diarrheal strategy in neonatal calves.

Cytosolic and Metallothionein-Bound Hepatic Metals and Detoxification in a Sentinel Teleost, Dules auriga, from Southern Rio de Janeiro, Brazil.

Dules auriga, a native Brazilian teleost, was applied as a sentinel species regarding metal contamination at Ilha Grande Bay, previously considered a reference site in Southeastern Brazil. Cytosolic (S50) and metallothionein-bound (HTS50) hepatic iron (Fe), zinc (Zn), copper (Cu), manganese (Mn), cadmium (Cd), and silver (Ag) were determined by inductively coupled plasma optical emission spectrometry (ICP-OES), while metallothionein (MT) concentrations were determined by polarography. Ag concentrations in both cytosolic fractions were below the limit of detection. All other HTS50 metal contents were significantly lower than S50 contents. No significant associations were found for MT. Fe and Mn S50 were positively and moderately correlated to total length, as well as HTS50 Mn, while total weight was correlated to both Mn fractions, suggesting that environmental Mn and Fe concentrations may influence fish growth. A moderate correlation between the condition factor and the S50 Cu fraction was observed, also indicating that Cu may affect fish growth. Inter-element correlations were observed, including between Cd, a toxic element, and Mn and Zn, both essential elements. Calculated molar ratios indicate that both Mn and Zn are in molar excesses compared with Cd, corroborating literature assessments regarding protective Mn and Zn effects against Cd. Lack of MT correlations suggests that metal concentrations may not be high enough to reach an MT induction threshold and that MT variability is probably linked to environmental metal concentrations. Therefore,the increased environmental contaminant levels observed in the study area indicate the need for biomonitoring efforts aiming at the application of efficient mitigation measures.

Inductively coupled plasma mass spectrometry determination of hepatic copper, manganese, selenium, and zinc concentrations in relation to sample amount and storage duration.

Trace mineral status is a critical component of bovine health. Impairment of physiological processes, caused by trace mineral toxicities or deficiencies, can be potential underlying factors of disease. Historically, the status of critical trace minerals, such as copper, manganese, selenium, and zinc, has been evaluated through the analysis of hepatic tissue. We assessed variation of these 4 elements between homogenized liver and samples of 0.02 g, 0.1 g, 0.5 g, and 1.0 g. We also evaluated concentration differences in copper, manganese, selenium, and zinc among samples stored under different durations. No differences in concentrations of copper, manganese, selenium, or zinc were observed among samples stored frozen for 3, 7, and 14 d post-collection. Statistical differences in concentrations of selenium and zinc were observed between 0.02-g biopsy samples and larger samples. Moisture content differed between 0.02-g biopsies and larger samples and over time. Results indicate that as little as 0.02 g of hepatic tissue dried to ~0.006 g is reliable for interpretation of trace mineral status and determination of toxicities and deficiencies in cattle pertaining to copper, manganese, selenium, and zinc, despite the small differences observed.

Hepatic copper and other trace mineral concentrations in dogs with hepatocellular carcinoma.

BackgroundHepatocellular carcinoma (HCC) is the most common primary liver tumor in dogs. Abnormalities in hepatic copper, iron, zinc, and selenium concentrations increase risk for HCC development in other species, but trace mineral concentrations have not been evaluated in dogs with HCC.ObjectivesTo investigate hepatic trace mineral concentrations in dogs with HCC.AnimalsArchived liver specimens from 85 dogs with HCC and 85 control dogs.MethodsRetrospective case‐control study. A histopathology database was searched to identify dogs with HCC (test population) and an age‐matched control population. Demographic information was retrieved, and H&E and rhodanine stained slides were reviewed for all cases. Copper, iron, zinc, and selenium concentrations were determined in noncancerous liver tissues (test and control population) and in HCC tissues (test population) using inductively coupled plasma mass spectrometry.ResultsHepatic copper concentrations (non‐neoplastic hepatic tissue) were greater in test population dogs (median, IQR; 294.9 μg/g, 233.5‐475.9 μg/g) than in control dogs (202.8 μg/g, 135.0‐295.3 μg/g; P < .001). Hepatic zinc concentrations in test (132.1 μg/g,108.6‐163.2 μg/g) and control dogs (151.5 μg/g, 117.1‐184.5 μg/g) also were different (P = .03). Within test population dogs, all trace mineral concentrations were decreased in the HCC tissue as compared to the non‐neoplastic hepatic tissue (all P < .001).Conclusions and Clinical ImportanceHepatic copper accumulation and other abnormalities in hepatic trace mineral concentrations could be involved in the pathogenesis of HCC in some dogs.

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.