Polaprezinc for prevention of oral mucositis in patients receiving chemotherapy followed by hematopoietic stem cell transplantation: A multi-institutional randomized controlled trial.

Oral mucositis is a common and distressing complication in patients receiving high-dose chemotherapy followed by hematopoietic stem cell transplantation (HSCT). We reported previously in a single-center retrospective analysis that zinc-L-carnosine (polaprezinc [PZ]) reduced the incidence of oral mucositis associated with HSCT. To verify the accuracy of the prophylactic effect of PZ against oral mucositis, we carried out a multi-institutional prospective randomized controlled study. Patients were randomly allocated to either the prevention group, in which PZ lozenge treatment was started before chemotherapy, or the control group, in which administration of PZ lozenges was initiated immediately after the onset of Grade 2 oral mucositis. Oral mucositis was evaluated daily from the start of chemotherapy to 35 days after transplantation. A total of 91 patients were enrolled, and 88 patients (47 in the control group and 41 in the prevention group) were eligible for data analysis. The incidence of Grade ≥2 but not Grade ≥3 oral mucositis was significantly reduced in the prevention group compared to the control group (44.7% in control group vs 22.0% in the prevention group, P = .025). There were no significant differences in the incidence rates of other adverse events or the rate of engraftment (95.6% vs 97.2%, P = .693) between the two groups. These findings suggest that PZ lozenge is effective for prophylaxis against Grade ≥2 oral mucositis associated with chemotherapy in patients undergoing HSCT without any influence on the HSCT outcome.

Time-dependent changes in proliferation, DNA damage and clock gene expression in hepatocellular carcinoma and healthy liver of a transgenic mouse model.

Hepatocellular carcinoma (HCC) is highly resistant to anticancer therapy and novel therapeutic strategies are needed. Chronotherapy may become a promising approach because it may improve the efficacy of antimitotic radiation and chemotherapy by considering timing of treatment. To date little is known about time-of-day dependent changes of proliferation and DNA damage in HCC. Using transgenic c-myc/transforming growth factor (TGFα) mice as HCC animal model, we immunohistochemically demonstrated Ki67 as marker for proliferation and γ-H2AX as marker for DNA damage in HCC and surrounding healthy liver (HL). Core clock genes (Per1, Per2, Cry1, Cry2, Bmal 1, Rev-erbα and Clock) were examined by qPCR. Data were obtained from samples collected ex vivo at four different time points and from organotypic slice cultures (OSC). Significant differences were found between HCC and HL. In HCC, the number of Ki67 immunoreactive cells showed two peaks (ex vivo: ZT06 middle of day and ZT18 middle of night; OSC: CT04 and CT16). In ex vivo samples, the number of γ-H2AX positive cells in HCC peaked at ZT18 (middle of the night), while in OSC their number remained high during subjective day and night. In both HCC and HL, clock gene expression showed a time-of-day dependent expression ex vivo but no changes in OSC. The expression of Per2 and Cry1 was significantly lower in HCC than in HL. Our data support the concept of chronotherapy of HCC. OSC may become useful to test novel cancer therapies.

In vitro hyperthermic effect of magnetic fluid on cervical and breast cancer cells.

Self-regulating temperature-controlled nanoparticles such as Mn-Zn ferrite nanoparticles based magnetic fluid can be a better choice for magnetic fluid hyperthermia because of its controlled regulation of hyperthermia temperature window of 43-45 °C. To test this hypothesis magnetic fluid with said properties was synthesized, and its effect on cervical and breast cancer cell death was studied. We found that the hyperthermia window of 43-45 °C was maintained for one hour at the smallest possible concentration of 0.35 mg/mL without altering the magnetic field applicator parameters. Their hyperthermic effect on HeLa and MCF7 was investigated at the magnetic field of 15.3 kA/m and frequency 330 kHz, which is close to the upper safety limit of 5 * 109 A/m s. We have tested the cytotoxicity of synthesized Mn-Zn ferrite fluid using MTT assay and the results were validated by trypan blue dye exclusion assay that provides the naked eye microscopic view of actual cell death. Since cancer cells tend to resist treatment and show re-growth, we also looked into the effect of multiple sessions hyperthermia using a 24 h window till 72 h using trypan blue assay. The multiple sessions of hyperthermia showed promising results, and it indicated that a minimum of 3 sessions, each of one-hour duration, is required for the complete killing of cancer cells. Moreover, to simulate an in vivo cellular environment, a phantom consisting of magnetic nanoparticles dispersed in 1 and 5% agarose gel was constituted and studied. These results will help to decide the magnetic fluid based hyperthermic therapeutic strategies using temperature-sensitive magnetic fluid.

Pre-dialysis serum creatinine as an independent predictor of responsiveness to zinc supplementation among patients on hemodialysis.

BACKGROUND: To investigate whether pre-dialysis level of serum creatinine (SCre) could indicate the responsiveness to zinc supplementation of patients on maintenance hemodialysis (MHD). METHODS: We retrospectively reviewed the results of our previous randomized study of 91 patients who had been on MHD and received zinc supplementation with either zinc acetate hydrate (ZAH; zinc, 50 mg/day) or polaprezinc (PPZ; zinc, 34 mg/day). A late response to zinc supplementation was defined as a serum zinc level of < 80 µg/dL three months after the study began. Patients were divided into two groups: late response (serum zinc level < 80 µg/dL) and early response (serum zinc level ≥ 80 µg/dL). Factors independently associated with a late response to zinc supplementation were determined using inverse probability of treatment weighting (IPTW) multivariate logistic analysis. RESULTS: Of 91 patients, 86 continued to receive zinc supplementation after three months. The mean pre-dialysis SCre level was 10.0 mg/dL. The number of patients with a late response and response to zinc supplementation was 32 and 54, respectively. There was a significant negative correlation between the pre-dialysis SCre and the Δserum zinc change for 3 months. (r = - 0.284, P = 0.008). IPTW multivariate analysis showed that a pre-dialysis SCre level ≥ 10.0 mg/dL (odds ratio, 3.71; 95% confidence interval; 1.24-11.1, P = 0.022) was an independent factor associated with a late response to zinc supplementation. CONCLUSIONS: Pre-dialysis SCre level was independently associated with responsiveness to zinc supplementation after three months in patients on MHD.

Supplementation of various zinc sources modify sexual development and testicular IGF family gene expression in pre-pubertal male Japanese quail.

Zinc plays an important role in the regulation of insulin-like growth factor-I (IGF-I). IGF system, in turn, has a key role in the development and functions of the reproductive organs. This research was performed to investigate the effects of different sources of zinc on IGF-I gene expression and testicular development in pre-pubertal male Japanese quail. A total of 512 unsexed day-old Japanese quail chicks were randomly divided into 16 groups (4 dietary treatments × 4 replicates) and kept for 35 days. The control group diet was not supplemented with zinc whereas the diets of three groups were supplemented with 25 mg kg-1 zinc oxide (ZnO), zinc oxide nanoparticle (ZnON), and zinc-methionine (Zn-Met). On days 28 and 35, one birds from each subgroup were weighed, bled, and euthanized to evaluate gonado-somatic index (GSI), testicular histology, serum testosterone concentration, cloacal gland index (CGI), and the testicular IGF family gene expression. The results showed that GSI was higher in ZnON (2.307) than control (1.619) on day 35 (P < .05). Germinal epithelium thickness was higher in ZnON (78.88 µm) and Zn-Met (79.73 µm) than control (67.73 µm) on day 35 (P < .05). On day 35, the testosterone concentration was lowest in the control (5.830 ng/ml, P < .05). The CGI of 35-day-old birds was higher in Zn-Met (411.28) than the control (307.59, P < .05). IGF-IR mRNA expression was highest in Zn-Met group on day 28. Therefore, supplementation of diet with Zn-methionine is superior to other sources of zinc for diet supplementation in immature Japanese quail.

[Transepidermal Water Loss (TEWL)-decreasing Effect by Administration of Zinc in the Elderly People].

In recent years, it has become clear that zinc deficiency is closely related in several skin disorders. In elderly people, chronic itch and dry skin are common. In addition, the zinc concentrations are known to decrease with age. Therefore, we examined the beneficial effects of oral zinc supplementation on dry skin and itch in elderly people. Patients 65 years of age or older who visited the Jose Clinic (Odai-town, Mie Pref.) with serum zinc concentrations below 80 µg/dL were enrolled in the study (low zinc group). The participants were administered zinc acetate hydrate for 12 weeks from the start of the study, and transepidermal water loss (TEWL) and stratum corneum moisture content measurements, blood collection, and itch evaluation were performed every 4 weeks. Patients in the control group had serum zinc concentrations of ≥80 µg/dL (the normal zinc group). Results showed that TEWL was significantly higher in the low zinc group than in the normal zinc group, indicating that skin barrier function is impaired in the low zinc group. Serum zinc concentrations increased and TEWL decreased significantly over the 12 weeks of treatment. In addition, a negative correlation was observed between serum zinc concentrations and TEWL. Our results indicate that zinc supplementation is effective to improve the skin barrier function in elderly people.

Incidence of Macular Atrophy after Untreated Neovascular Age-Related Macular Degeneration: Age-Related Eye Disease Study Report 40.

PURPOSE: To report the natural history of untreated neovascular age-related macular degeneration (nAMD) regarding subsequent macular atrophy. DESIGN: Prospective cohort within a randomized, controlled trial of oral micronutrient supplements. PARTICIPANTS: Age-Related Eye Disease Study (AREDS) participants (55-80 years) who demonstrated nAMD during follow-up (1992-2005), prior to anti-vascular endothelial growth factor (VEGF) therapy. METHODS: Color fundus photographs were collected at annual study visits and graded centrally for late age-related macular degeneration (AMD). Incident macular atrophy after nAMD was examined by Kaplan-Meier analysis and proportional hazards regression. MAIN OUTCOME MEASURES: Incident macular atrophy after nAMD. RESULTS: Of the 4757 AREDS participants, 708 eyes (627 participants) demonstrated nAMD during follow-up and were eligible. The cumulative risks of incident macular atrophy after untreated nAMD were 9.6% (standard error, 1.2%), 31.4% (standard error, 2.2%), 43.1% (standard error, 2.6%), and 61.5% (standard error, 4.3%) at 2, 5, 7, and 10 years, respectively. This corresponded to a linear risk of 6.5% per year. The cumulative risk of central involvement was 30.4% (standard error, 3.2%), 43.4% (standard error, 3.8%), and 57.0% (standard error, 4.8%) at first appearance of atrophy, 2 years, and 5 years, respectively. Geographic atrophy (GA) in the fellow eye was associated with increased risk of macular atrophy (hazard ratio [HR], 1.70; 95% confidence interval [CI], 1.17-2.49; P = 0.006). However, higher 52-single nucleotide polymorphism AMD genetic risk score was not associated with increased risk of macular atrophy (HR, 1.03; 95% CI, 0.90-1.17; P = 0.67). Similarly, no significant differences were observed according to SNPs at CFH, ARMS2, or C3. CONCLUSIONS: The rate of incident macular atrophy after untreated nAMD is relatively high, increasing linearly over time and affecting half of eyes by 8 years. Hence, factors other than anti-VEGF therapy are involved in atrophy development, including natural progression to GA. Comparison with studies of treated nAMD suggests it may not be necessary to invoke a large effect of anti-VEGF therapy on inciting macular atrophy, although a contribution remains possible. Central involvement is present in one third of eyes at the outset (similar to pure GA) and increases linearly to half at 3 years.

Zinc source modulates zootechnical characteristics, intestinal features, humoral response, and paraoxonase (PON1) activity in broilers.

The current experiment was performed to find the potential effect of inorganic and organic forms of zinc (Zn) on growth, intestinal histomorphology, immune response, and paraoxonase (PON1) activity in broiler. In this experiment, a total of 450 broiler chickens were assigned to four experimental and control groups. The birds received organic Zn at the rate of 50 mg/kg (OZ-50) and 60 mg/kg (OZ-60) or inorganic Zn at the rate of 50 mg/kg (IZ-50) and 60 mg/kg (IZ-60) for an experimental period of 30 days. Significantly (P < 0.05) higher feed consumption, body weight, feed conversion ratio, and production efficiency factor (PEF) were recorded in OZ-50. Similarly, antibody titer against infectious bronchitis (IB) and PON1 activity was higher (P < 0.05) in OZ-50 compared with the control group. In addition, significantly (P < 0.05) higher villus dimensions and goblet cell count were recorded for the group OZ-50 compared with other treatments. It was concluded that the organic form of Zn was superior in improving the growth, histological features of intestines, humoral response, and PON1 activity in broiler.

Zinc abrogates anticancer drug tamoxifen-induced hepatotoxicity by suppressing redox imbalance, NO/iNOS/NF-ĸB signaling, and caspase-3-dependent apoptosis in female rats.

Tamoxifen (TAM) is used in breast cancer chemotherapy since its approval by the Food and Drug Administration in 1977. However, TAM therapy is accompanied with hepatotoxicity - a source of worry to clinicians. Oxidative stress and inflammation are the major implicated mechanisms contributing to TAM hepatotoxicity. In this study, we explored whether zinc (Zn) supplementation could prevent TAM-induced hepatotoxicity in female Wistar rats. Rats were subjected to oral pretreatment of Zn (100 mg/kg body weight (b.w.)/day) for 14 days against hepatic toxicity induced by single intraperitoneal administration of TAM (50 mg/kg b.w.) on day 13. TAM markedly elevated serum liver enzymes, whereas total protein and albumin considerably reduced. TAM caused prominent depletion of hepatic-reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activity. Also, TAM significantly increased malondialdehyde (MDA) level. Further, it raised liver levels of tumor necrosis factor-α (TNF-α), interleukin-1ß, (IL-1ß), interleukin-6 (IL-6), and nitric oxide (NO) confirmed by the liver histopathological alterations. The mechanistic inflammatory expression of inducible nitric oxide synthase (iNOS) and nuclear factor-kappa B (NF-ĸB), and expression of caspase-3 protein prominently increased. Zinc supplementation significantly modulated serum liver function markers, antioxidant enzymes, and GSH and MDA levels. Zinc downregulated the expression of cytokines, NO, iNOS, NF-ĸB and caspase-3, and ameliorated histopathological changes. Zinc protects against TAM-induced hepatotoxicity; it may serve as an adjuvant supplement for female patients undergoing TAM chemotherapy.

Comparing the Influence of High Doses of Different Zinc Salts on Oxidative Stress and Energy Depletion in IPEC-J2 Cells.

The current study aimed to investigate the influence of four supplemental zinc salts (chelated: Zn glycine; non-chelated: Zn sulfate, Zn citrate, Zn gluconate) among different zinc concentrations (30-300 µM) on cell proliferation, oxidative stress, and energy depletion in intestinal porcine jejunum epithelial cells (IPEC-J2). Different zinc salts affected cell viability in a time- and dose-dependent manner, which was mainly dependent on the uptake of intracellular Zn2+. Intracellular Zn2+ of Zn sulfate has taken up almost twice as high as Zn glycine when cells were loaded with 100-200 µM zinc. After loading cells with 300 µM zinc, Zn glycine and Zn sulfate had a similar trend in accumulation of Zn2+. When the intracellular Zn2+ overloads, cells will gradually be damaged and subsequently die bearing biochemical features of necrosis or late apoptosis. Meanwhile, obviously, increased levels of intracellular ROS, mitochondrial ROS, MDA, and NO and decreased levels of GSH were observed. Excessive intracellular Zn2+ significantly decreased mitochondria membrane potential accompanied by an obvious loss of ATP and NAD+ levels. Overall, exposure to high doses of zinc salts caused cell damage, which was mainly dependent on the uptake of Zn2+. Zinc overload induced oxidative stress and energy depletion in IPEC-J2 cells, and the cell damage with non-chelated zinc addition was more serious than Zn glycine.

Association of Total Zinc Intake with Myopia in U.S. Children and Adolescents.

SIGNIFICANCE: This present study advances our knowledge on the role of lifestyle factors in myopia (short-sightedness), specifically dietary factors. It has been suggested in previous studies that lower zinc status is associated with myopia; however, this article shows no relationship between dietary zinc intake and myopia in U.S. adolescents. PURPOSE: It has been suggested that low zinc levels may contribute to the development of myopia. The aim of the present study is to examine, for the first time in a Western population, the association of total dietary and supplement zinc intake with myopia. METHODS: A total of 1095 children/adolescents aged 12 to 19 years who participated in the U.S. National Health and Nutrition Examination Survey from 2007 to 2008 were enrolled in this study. Multivariate logistic regression analysis was performed to examine the relationship between total zinc intake and myopia after adjustment for potential confounders. In addition, the association between total zinc intake and spherical equivalent refractive error was examined in the myopia group through multiple linear regression. RESULTS: Among study participants, 30% were found to be myopic (≤-1.00 D). Although median total daily zinc intake was lower among myopes (10.8 [10.2] mg/d) than among nonmyopes (11.1 [10.8] mg/d), the difference was not statistically significant (P = .11). In multiple logistic regression analyses, zinc and copper intakes were not significantly associated with myopia after adjustment for age, sex, body mass index, ethnicity, family income, recreational activity, copper intake, and daily energy intake (in kilocalories per day). In multiple linear regression, spherical equivalent refractive error was not associated with total zinc intake in the myopic group after adjustment for confounding factors (P = .13). CONCLUSIONS: In contrast to previous Asian studies, total zinc intake is not associated with the presence of myopia in U.S. adolescents/children.

No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or ß-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2: Age-Related Eye Disease Study 2 Report No. 18.

PURPOSE: To assess whether genotypes at 2 major loci associated with age-related macular degeneration (AMD), complement factor H (CFH), or age-related maculopathy susceptibility 2 (ARMS2), modify the response to oral nutrients for the treatment of AMD in the Age-Related Eye Disease Study 2 (AREDS2). DESIGN: Post hoc analysis of a randomized trial. PARTICIPANTS: White AREDS2 participants. METHODS: AREDS2 participants (n = 4203) with bilateral large drusen or late AMD in 1 eye were assigned randomly to lutein and zeaxanthin, omega-3 fatty acids, both, or placebo, and most also received the AREDS supplements. A secondary randomization assessed modified AREDS supplements in 4 treatment arms: lower zinc dosage, omission of ß-carotene, both, or no modification. To evaluate the progression to late AMD, fundus photographs were obtained at baseline and annual study visits, and history of treatment for late AMD was obtained at study visits and 6-month interim telephone calls. Participants were genotyped for the single-nucleotide polymorphisms rs1061170 in CFH and rs10490924 in ARMS2. Bivariate frailty models using both eyes were conducted, including a gene-supplement interaction term and adjusting for age, gender, level of education, and smoking status. The main treatment effects, as well as the direct comparison between lutein plus zeaxanthin and ß-carotene, were assessed for genotype interaction. MAIN OUTCOME MEASURES: The interaction between genotype and the response to AREDS2 supplements regarding progression to late AMD, any geographic atrophy (GA), and neovascular AMD. RESULTS: Complete data were available for 2775 eyes without baseline late AMD (1684 participants). The participants (mean age ± standard deviation, 72.1±7.7 years; 58.5% female) were followed up for a median of 5 years. The ARMS2 risk allele was associated significantly with progression to late AMD and neovascular AMD (P = 2.40 × 10-5 and P = 0.002, respectively), but not any GA (P = 0.097). The CFH risk allele was not associated with AMD progression. Genotype did not modify significantly the response to any of the AREDS2 supplements. CONCLUSIONS: CFH and ARMS2 risk alleles do not modify the response to the AREDS2 nutrient supplements with respect to the progression to late AMD (GA and neovascular AMD).

Tumor-facing hepatocytes significantly contribute to mild hyperthermia-induced targeting of rat liver metastasis by PLGA-NPs.

The effect of mild hyperthermia (MHT) on nanoparticle (NP) accumulation in rat model liver metastasis and the contribution of neoplastic and non-neoplastic cells were characterized. CdSe/ZnS QD-doped poly(lactic-co-glycolic acid) (PLGA) NPs (155 ±â€¯10 nm) were delivered via the ileocolic vein to metastatic livers 15 min after localized MW irradiation (1 min, 41 °C) or in normothermia (37 °C, NT). Quantitative analysis of tissue sections by confocal fluorescence microscopy 1 h after NP injection showed no NP tumor accumulation in NT. On the contrary, MHT increased NP association with tumor, compared to normal tissue. Counterstaining of specific markers showed that the MHT effect is due to an increased NP endocytosis not only by tumor cells, but also by hepatocytes at the growing tumor edge and, to a minor extent, by tumor-associated macrophages. High-NP capturing hepatocytes, close to the tumor, may be a relevant phenomenon in MHT-induced increased targeting of NPs to liver metastasis, influencing their therapeutic efficacy.

Zinc citrate incorporation with whey protein nanoparticles alleviate the oxidative stress complication and modulate gene expression in the liver of rats.

This study aimed to evaluate the hepatoprotective effect of whey protein nanoparticles (WP-NPs) coated Zinc citrate (Zn) against oxidative stress complications and disturbances in gene expression in rats treated with CCl4. WP-NPs were used to coat Zn at three levels and amino acids content was determined in WP-NPs and the fabrications. Seven groups of male albino rats included the control group, CCl4-treated group (0.5 ml/100 g b.w) and the groups treated with CCl4 plus WP-NPs, Zn and the three Zn-WP-NPs fabrications. Blood and liver samples were collected for different analysis. Particles sizes were 95, 142, 196 and 228 nm and zeta potential values were -95, -114, -85 and -79 for WP-NPs and the three Zn-WP-NPs fabrications, respectively. Twelve amino acids were found in WP-NPs and this number was decreased by increasing Zn content. WP-NPs, Zn and the Zn coated WP-NPs counteracted the disturbances in biochemical, parameters, gene expression and histological changes in CCl4-treated rats and Zn-WP-NPs was more effective at the low dose. It could be concluded that WP-NPs enhance the effect of Zn and can be used for coating Zn in the preparation of Zn supplementation to enhance its effect and counteract the side effect of excess Zn.

Effects of Dietary Organic, Inorganic, and Nanoparticulate Zinc on Rainbow Trout, Oncorhynchus mykiss Larvae.

The present study was conducted to investigate the effects of different dietary zinc sources on growth performance, survival, and body composition of larval rainbow trout, Oncorhynchus mykiss. A total of 3240 larvae with an average weight of 82.3 ± 11.6 mg were randomly divided into four groups by three replicates and were fed for 70 days. Organic zinc (Zn-proteinate, Bioplex Zn®), mineral zinc (ZnSO4), and nanoparticulate zinc (ZnO-NPs) were each added to the basal diet at 50-mg/kg diet. In all of the zinc-supplemented groups, final body weight (FBW) and weight gain (WG) increased significantly (P < 0.05) compared to the control at the termination of the feeding trial. There was no significant difference in specific growth rate (SGR) in experimental groups. Fish fed with mineral and nanoparticulate zinc, respectively, demonstrated the highest and lowest survival rates (P < 0.05) as compared to other experimental diets. Feed conversion ratio (FCR) significantly decreased (P < 0.05) in groups fed with organic and mineral zinc. There were no significant differences in protein, lipid, moisture, and ash content among fish fed the experimental diets. Fish fed mineral zinc showed the highest (P < 0.05) zinc content in the whole body than the other groups. The data of the present study confirm positive effects of the use of 50 mg kg-1 of zinc sources in early diet to enhance growth performance of rainbow trout larvae.

Zinc Supplementation Stimulates Red Blood Cell Formation in Rats.

In rats, mice, and humans, it is known that zinc deficiency may be related to anemia, and zinc supplementation influences hemoglobin production. Our previous studies indicate that in fish, zinc supplementation stimulates red blood cell (RBC) formation (erythropoiesis). However, it is not clear whether the mechanism of zinc-induced erythropoiesis stimulation in fish also occurs in rats. We induced anemia in rats using phenylhydrazine (PHZ) and injected either saline or ZnSO4 solution. We found that an appropriate amount of zinc stimulated erythropoiesis in the PHZ-induced anemic rats. The effects of ZnSO4 injection were dose-dependent. When the concentration of ZnSO4 was higher than 2.8 mg zinc/kg body weight, the RBC level of the anemic rats increased from 60 ± 7% to 88 ± 10% that of the normal rats in two days. Rat bone marrow cells with or without ZnCl2 supplementation were cultured in suspension in vitro. In the cell culture when the zinc concentration was at 0.3 mM, a 1.6-fold proliferation of nascent immature reticulocytes (new RBCs) was observed after one day. In the rat blood, zinc was combined with serum transferrin to induce erythropoiesis. The stimulation of RBC formation by zinc appears to be common among different animals.

Zinc mitigates renal ischemia-reperfusion injury in rats by modulating oxidative stress, endoplasmic reticulum stress, and autophagy.

Oxidative stress is a major factor involved in the pathogenesis of renal ischemia/reperfusion (I/R). Exogenous zinc (Zn) was suggested as a potent antioxidant; however, the mechanism by which it strengthens the organ resistance against the effects of reactive oxygen species (ROS) is not yet investigated. The present study aims to determine whether acute zinc chloride (ZnCl2 ) administration could attenuate endoplasmic reticulum (ER) stress, autophagy, and inflammation after renal I/R. Rats were subjected to either sham operation (Sham group, n = 6), or 1 hr of bilateral ischemia followed by 2 hr of reperfusion (I/R groups, n = 6), or they received ZnCl2 orally 24 hr and 30 min before ischemia (ZnCl2 group, n = 6). Rats were subjected to 1 hr of bilateral renal ischemia followed by 2 hr of reperfusion (I/R group, n = 6). Our results showed that ZnCl2 enhances renal function and reduces cytolysis (p < 0,05). In addition, it increased significantly the activities of antioxidant enzymes (SOD, CAT, and GPX) and the level of GSH in comparison to I/R (p < 0,05). Interestingly, ZnCl2 treatment resulted in significant decreased ER stress, as reflected by GRP78, ATF-6,p-eIF-2α, XPB-1, and CHOP downregulaion. Rats undergoing ZnCl2 treatment demonstrated a low expression of autophagy parameters (Beclin-1 and LAMP-2), which was correlated with low induction of apoptosis (caspase-9, caspase-3, and p-JNK), and reduction of inflammation (IL-1ß, IL-6, and MCP-1) (p < 0,05). In conclusion, we demonstrated the potential effect of Zn supplementation to modulate ER pathway and autophagic process after I/R.

Effects of Different Sources and Levels of Zinc on Growth Performance, Nutrient Digestibility, and Fur Quality of Growing-Furring Male Mink (Mustela vison).

The objective of this study was to investigate the effects of different sources and levels of zinc (Zn) on growth performance, nutrient digestibility, serum biochemical parameters, and fur quality in growing-furring male mink. Animals in the control group were fed a basal diet with no Zn supplementation. Mink in the other nine treatments were fed the basal diet supplemented with Zn from either grade Zn sulfate (ZnSO4·7H2O), Zn glycinate (ZnGly), or Zn pectin oligosaccharides (ZnPOS) at concentrations of either 100, 300, or 900 mg Zn/kg dry matter. One hundred and fifty healthy 15-week-old male mink were randomly allocated to ten dietary treatments (n = 15/group) for a 60-day trial from mid-September to pelting in December. Mink in the Zn-POS groups had higher average daily gain than those in the control group (P < 0.05). Zn source slightly improved the feed/gain (P = 0.097). N retention was increased by Zn addition (P < 0.05). Mink supplemented with dietary Zn had higher (P < 0.05) pancreas Zn level than the control group. Fur length was greater (P < 0.05) in ZnGly and ZnPOS groups compared with the control. In addition, fur length and fur density increased (linear, P < 0.05) with Zn supplementation in the diet. In conclusion, our data show that dietary Zn addition improves growth performance by increasing nitrogen retention and fat digestibility in growing-furring mink and Z-POS is equally bioavailable to mink compared to ZnGly.

Zinc Supplementation Improves Glucose Homeostasis in High Fat-Fed Mice by Enhancing Pancreatic ß-Cell Function.

Zinc is an essential component of the insulin granule and it possibly modulates insulin secretion and signaling. Since insulin resistance is a hallmark in the development of type 2 diabetes mellitus, this study aimed at investigating if zinc supplementation is able to improve glucose tolerance and ß-cell function in a model of insulin resistance. Male C57BL/6 mice were distributed in four groups according to the diet: normal fat (NF); normal fat supplemented with ZnCl2 (NFZ); high-fat (HF); and, high-fat chow supplemented with ZnCl2 (HFZ). Intraperitoneal glucose (ipGTT) and insulin (ipITT) tolerance, glycemia, insulinemia, HOMA-IR, and HOMA-ß were determined after 15 weeks in each diet. Glucose-stimulated insulin secretion (GSIS) was investigated in isolated islets. The insulin effect on glucose uptake, metabolism, and signaling was investigated in soleus muscle. ZnCl2 did not affect body mass or insulin sensitivity as assessed by ipITT, HOMA-IR, muscle glucose metabolism, and Akt and GSK3-ß phosphorylation. However, glucose tolerance, HOMA-ß, and GSIS were significantly improved by ZnCl2 supplementation. Therefore, ZnCl2 supplementation improves glucose homeostasis in high fat-fed mice by a mechanism that enhances ß-cell function, rather than whole-body or muscle insulin sensitivity.