Actively Targeted Magnetothermally Responsive Nanocarriers/Doxorubicin for Thermochemotherapy of Hepatoma.

Nanodrug-delivery systems modified with targeting molecules allow antitumor drugs to localize to tumor sites efficiently. CD147 protein is expressed highly on hepatoma cells. Firstly, we synthesized magnetothermally responsive nanocarriers/doxorubicin (MTRN/DOX) which was composed of manganese zinc (Mn-Zn) ferrite magnetic nanoparticles, amphiphilic and thermosensitivity copolymer drug carriers together with DOX. Then CD147-MTRN/DOX was formed with MTRN/DOX and monoclonal antibody that specifically binds to CD147 protein. It could target hepatoma cells actively and improve the DOX concentration in the tumor sites. Subsequently, an external alternating magnetic field elevated the temperature of the thermomagnetic particles, resulting in structural changes in the thermosensitive copolymer drug carriers, thereby releasing DOX. Hence, CD147-MTRN/DOX could enhance the responsiveness of hepatoma cells to the pre-existing chemotherapy drugs owing to active targeting combined synergistically with thermotherapy and chemotherapy, which has more significant anticancer effects than MTRN/DOX.

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.

Preparation, properties and anticancer effects of mixed As4S4/ZnS nanoparticles capped by Poloxamer 407.

Arsenic sulfide compounds have a long history of application in a traditional medicine. In recent years, realgar has been studied as a promising drug in cancer treatment. In this study, the arsenic sulfide (As4S4) nanoparticles combined with zinc sulfide (ZnS) ones in different molar ratio have been prepared by a simple mechanochemical route in a planetary mill. The successful synthesis and structural properties were confirmed and followed via X-ray diffraction and high-resolution transmission electron microscopy measurements. The morphology of the particles was studied via scanning electron microscopy and transmission electron microscopy methods and the presence of nanocrystallites was verified. For biological tests, the prepared As4S4/ZnS nanoparticles were further milled in a circulation mill in a water solution of Poloxamer 407 (0.5wt%), in order to cover the particles with this biocompatible copolymer and to obtain stable nanosuspensions with unimodal distribution. The average size of the particles in the nanosuspensions (~120nm) was determined by photon cross-correlation spectroscopy method. Stability of the nanosuspensions was determined via particle size distribution and zeta potential measurements, confirming no physico-chemical changes for several months. Interestingly, with the increasing amount of ZnS in the sample, the stability was improved. The anti-cancer effects were tested on two melanoma cell lines, A375 and Bowes, with promising results, confirming increased efficiency of the samples containing both As4S4 and ZnS nanocrystals.

Interaction between nanoparticles generated by zinc chloride treatment and oxidative responses in rat liver.

The aim of the present study was to investigate the interaction of zinc chloride (3 mg/kg, intraperitoneally [ip]) in rat liver in terms of the biosynthesis of nanoparticles. Zinc treatment increased zinc content in rat liver. Analysis of fluorescence revealed the presence of red fluorescence in the liver following zinc treatment. Interestingly, the co-exposure to zinc (3 mg/kg, ip) and selenium (0.20 mg/L, per os [by mouth]) led to a higher intensity of red fluorescence compared to zinc-treated rats. In addition, X-ray diffraction measurements carried out on liver fractions of zinc-treated rats point to the biosynthesis of zinc sulfide and/or selenide nanocomplexes at nearly 51.60 nm in size. Moreover, co-exposure led to nanocomplexes of about 72.60 nm in size. The interaction of zinc with other mineral elements (S, Se) generates several nanocomplexes, such as ZnS and/or ZnSe. The nanocomplex ZnX could interact directly with enzyme activity or indirectly by the disruption of mineral elements' bioavailability in cells. Subacute zinc or selenium treatment decreased malondialdehyde levels, indicating a drop in lipid peroxidation. In addition, antioxidant enzyme assays showed that treatment with zinc or co-treatment with zinc and selenium increased the activities of glutathione peroxidase, catalase, and superoxide dismutase. Consequently, zinc complexation with sulfur and/or selenium at nanoscale level could enhance antioxidative responses, which is correlated to the ratio of number of ZnX nanoparticles (X=sulfur or X=selenium) to malondialdehyde level in rat liver.

In vivo monitoring of distributional transport kinetics and extravasation of quantum dots in living rat liver.

Although the unique optical properties of surface-modified quantum dots (QDs) have attracted wide interest in molecular biology and bioengineering, there are very few reports of their in vivo biodistribution, due to a lack of analytical techniques for characterizing the dynamic variation of QDs in living animals. In this study, we used an in vivo online monitoring system and a batch-wise elemental analytical method to investigate the biodistribution/extravasation of various surface-modified CdTeSe/ZnS (QDs) in rat liver. It is found that the surface modification dictated not only the blood retention profile but also the degree of extravasation and the clearance of extracellular QDs, making it an important variable for regulating the transfer and exchange process of QDs among three physiological compartments-bloodstream, extracellular space and Kupffer cells/hepatocytes.

Bioavailability of zinc sources and their interaction with phytates in broilers and piglets.

Zinc (Zn) is essential for swine and poultry and native Zn concentrations in feedstuffs are too low to meet their Zn requirement. Dietary Zn bioavailability is affected by phytate, phytase and Zn supplemented in organic form is considered as more bioavailable than inorganic sources. A meta-analysis using GLM procedures was processed using broiler and piglet databases to investigate, within the physiological response of Zn, (1) the bioavailability of inorganic and organic Zn sources (Analysis I); (2) the bioavailability of native and inorganic Zn dependent from dietary phytates, vegetal and supplemental phytase activity (Analysis II). Analysis I: the bioavailability of organic Zn relative to inorganic Zn sources ranged, depending on the variable, from 85 to 117 never different from 100 (P > 0.05). The coefficients of determination of the regressions were 0.91 in broilers and above 0.89 in piglets. Analysis II: in broilers, bone Zn was explained by supplemental Zn (linear and quadratic, P < 0.001) and by supplemental phytase (linear, P < 0.001). In piglets, the interaction between dietary Zn and phytates/phytases was investigated by means of a new variable combining dietary phytic phosphorus (PP) and phytase activity. This new variable represents the remaining dietary PP after its hydrolysis in the digestive tract, mainly due to phytase and is called non-hydrolyzed phytic phosphorus (PP(NH)). Bone Zn was increased with native Zn (P < 0.001), but to a lower extent in high PP or low phytase diets (ZN(N) × PP(NH), P < 0.001). In contrast, the increase in bone zinc in response to supplemental Zn (P < 0.001) was not modulated by PP(NH) (P > 0.05). The coefficients of determination of the regressions were 0.92 in broilers and above 0.92 in piglets. The results from the two meta-analyses suggest that (1) broilers and piglets use supplemented Zn, independent from Zn source; (2) broiler use native Zn and the use is slightly enhanced with supplemental phytase; (3) however, piglets are limited in the use of native Zn because of the antagonism of non-hydrolyzed dietary phytate. This explains the higher efficacy of phytase in improving Zn availability in this specie.

Effect of zinc supplementation on bone metabolism in male rats chronically exposed to cadmium.

The aim of the present study is to investigate, based on the rat model of moderate and relatively high human exposure to cadmium (Cd), whether zinc (Zn) supplementation may prevent Cd-induced disorders in bone metabolism. For this purpose, male Wistar rats received Cd (5 and 50mg/l) or/and Zn (30 and 60mg/l) in drinking water for 6 and 12 months. Bone densitometry and biochemical markers of bone turnover were used to assess the effects of Cd or/and Zn. Bone mineral content (BMC) and density (BMD) were measured in the femur. Serum osteocalcin (OC) and alkaline phosphatase in trabecular (bT-ALP) and cortical (bC-ALP) bone were determined as bone formation markers, and carboxy-terminal cross-linking telopeptides of type I collagen (CTX) in serum were measured as bone resorption marker. Serum concentration of calcium (Ca) and its renal handling, as well as Zn and Cd concentrations in the serum/blood, urine and femur were evaluated as well. The exposure to 5 and 50mg Cd/l (0.340+/-0.026 and 2.498+/-0.093mg Cd/kg body wt/24h, respectively), in a dose and duration dependent manner, affected bone turnover (inhibited bone formation and stimulated its resorption) and disturbed bone mineralization (decreased BMC, BMD and Zn concentration). Zn supply at the concentration of 30 and 60mg/l (1.904+/-0.123 and 3.699+/-0.213mg/kg body wt/24h, respectively) during Cd exposure influenced the Cd-induced disorders in bone metabolism. Zn administration to the Cd-exposed rats enhanced the bone ALP activity and prevented Cd-induced bone resorption, but had no statistically significant effect on BMC and BMD; however, mean values of the densitometric parameters in the rats receiving both Cd and Zn were higher than in those treated with Cd alone. Moreover, Zn supplementation at both levels of Cd exposure was found to prevent Cd accumulation in the femur and the Cd-induced decrease in bone Zn concentration. The results of the present study allow the conclusion that Zn supplementation during Cd exposure may partly protect from disorders in bone metabolism. The influence of Zn may be accompanied by its ability to prevent Cd-induced Zn deficiency and to decrease Cd accumulation in bone tissue. The findings seem to indicate that enhanced dietary intake of Zn in subjects chronically exposed to moderate and relatively high Cd levels may have a protective influence on the skeleton.

Bioavailability, biodistribution, and toxicity of BioZn-AAS(1): a new zinc source. comparative studies in rats.

Food fortification with a proper zinc compound is an economic and effective strategy to prevent zinc deficiency. BioZn-AAS, a zinc gluconate stabilized with glycine, was compared with zinc sulfate (reference standard), zinc hydroxide, and zinc gluconate, all of them labeled with (65)Zn. This preclinical study was performed on Sprague-Dawley rats of both sexes, and the administered dose was 85 microg/kg of zinc. Bioavailability studies showed that absorption of BioZn-AAS was not statistically different than absorption from other sources in female rats (25.65% +/- 2.20% for BioZn-AAS, 28.24% +/- 4. 60% for ZnSO(4), 24.91% +/- 4.02% for Zn[OH](2), and 25.51% +/- 2. 70% for Zn-gluconate). In the case of the male rats, absorption of BioZn-AAS (27.97% +/- 4.20%) was higher (P<0.05) than that from the other compounds (23.15% +/- 2.90% for ZnSO(4), 22.62% +/- 3.90% for Zn[OH](2), and 22.30% +/- 3.90% for Zn-gluconate). Biodistribution studies demonstrated that the zinc from BioZn-AAS followed the same metabolic pathway as zinc from the other sources. Toxicity studies were performed with 50 female and 50 male rats. The value of oral lethal dose 50 (LD(50)) was 2000 mg/kg for female rats and 1900 mg/kg for male rats. Therefore, we conclude that BioZn-AAS has adequate properties to be considered a proper zinc compound for food fortification or dietary supplementation.

Equivalent uptake of organic and inorganic zinc by monkey kidney fibroblasts, human intestinal epithelial cells, or perfused mouse intestine.

Zinc (Zn) is recognized as an essential nutrient, and is added as a supplement to animal and human diets. There are claims that zinc methionine (ZnMet) forms a stable complex that is preferentially transported into tissues, and this has contributed to uncertainty about conflicting reports on the bioavailability of various Zn compounds. This study evaluated the cellular and intestinal uptake of inorganic and organic forms of Zn. Steady-state uptake of 65Zn by human intestine epithelial cells, and monkey kidney fibroblasts was not significantly different with zinc chloride (ZnCl2), ZnMet, or zinc propionate (ZnProp) (P > 0.05). Uptake of 65Zn from zinc chelated with EDTA was significantly lower (P < 0.01). In live mice, 65Zn uptake by perfused intestine and deposition in intestine and liver showed no significant difference between ZnCl2 and ZnMet. Equimolar [65Zn]methionine and zinc[35S]methionine were prepared according to a patented method that yields "complexed" Zn. Cellular uptake of the radiolabeled methionine was <0.1% of the radiolabeled Zn from these complexes, indicating separate uptake of the Zn and methionine. Gel filtration did not distinguish between 65Zn in ZnCl2, ZnProp, or reagent ZnMet, though feed-grade ZnMet containing >10% protein did give a higher-mol-wt form of 65Zn. Results of this study show equivalent uptake of Zn from inorganic and organic compounds, and support recent feed trials on Zn bioavailability.

Bioavailability of zinc from inorganic and organic sources for pigs fed corn-soybean meal diets.

Two experiments were conducted with pigs 1) to determine the effect of supplemental Zn on growth performance, bone Zn, and plasma Zn in pigs fed Zn-unsupplemented, corn-soybean meal diets and 2) to assess bioavailability of Zn from inorganic and organic Zn sources. In both experiments, weanling pigs were fed a diet with no supplemental Zn for 5 wk to deplete their Zn stores. In Exp. 1, 192 pigs were fed a corn-soybean meal diet (growing diet, 32 mg/kg of Zn; finishing diet, 27 mg/kg of Zn) supplemented with feed-grade ZnSO4.H2O to provide 0, 5, 10, 20, 40, and 80 mg/kg of supplemental Zn. Supplemental Zn did not affect weight gain, feed intake, or gain/feed during either the growing or the finishing period (P > .05). However, bone and plasma Zn concentrations increased linearly (P < .01) in response to supplemental Zn at dietary Zn levels between 27 mg/kg (basal) and 47 mg/kg (breakpoint). In Exp. 2, three levels of supplemental Zn from ZnSO4.H2O (0, 7.5, and 15 mg/kg of supplemental Zn) were used to construct a standard curve (metacarpal, coccygeal vertebrae, and plasma Zn concentrations regressed on supplemental Zn intake; R2 = .93, .89, and .82, respectively). From the standard curve, the bone and plasma Zn concentrations obtained from pigs fed 15 mg/kg of supplemental Zn from ZnO and 7.5 mg/kg of supplemental Zn from Zn-methionine (ZnMET) and Zn-lysine (ZnLYS) were used to calculate bioavailable Zn via multiple linear regression, slope-ratio analysis. The estimates of Zn bioavailability differed depending on which variable was used. Overall trends indicated the following rankings: ZnSO4.H2O > ZnMet > ZnO > ZnLys.

Acrodermatitis enteropathica, zinc metabolism, copper status, and immune function.

OBJECTIVE: To study zinc metabolism, copper status, and immune function in a patient with acrodermatitis enteropathica. RESEARCH DESIGN: Case report. PATIENT: A 16-year-old boy with acrodermatitis enteropathica. INTERVENTION: Change of zinc supplementation dosage from 1000 to 525 mumol/d. MEASUREMENTS AND RESULTS: Zinc metabolism was studied with an oral dose of zinc chloride Zn 65 and whole-body counting at both zinc dosages. Zinc, copper status, and immune indexes were also measured at both dosages. The higher dosage of zinc supplementation was found to induce a state of low copper status and immune dysfunction. Lowering the dosage normalized these indexes. Zinc absorption in this patient was found to be within the reference range for healthy subjects. At the lower dosage, zinc retention and the rate of whole-body turnover also normalized. These results suggest that the primary lesion in acrodermatitis enteropathica is a cellular defect in zinc metabolism rather than an impairment of zinc absorption. CONCLUSION: Zinc and copper status and immune function should be monitored regularly in patients with acrodermatitis enteropathica to provide a proper dosage of zinc during different physiologic stages.

Stress induction affects copper and zinc balance in calves fed organic and inorganic copper and zinc sources.

This study determined whether Cu and Zn balance was affected by feeding either Zn methionine (ZnMet) + Cu lysine (CuLys) or Zn sulfate (ZnSO4) + Cu sulfate (CuSO4) before and after stressing calves. Eight Charolais crossbred steer calves weighting 167 +/- 5 kg were randomly assigned to two treatments in a crossover experimental design. The millet hay and soybean meal diet when supplemented with the inorganic salts provided 9.2 ppm of Cu and 36.6 ppm of Zn or when fortified with the metal complexes contained 10.5 ppm of Cu and 36.6 ppm of Zn. Gentled calves were fed their respective diets for 28 d before an 18-d mineral balance trial was conducted. Collection consisted of five periods: 1) a 5-d baseline period, 2) 3 d of no Cu and Zn supplement, 3) 3 d of stress consisting of feed and water restriction and ACTH (80 IU) injections i.m. every 8 h, 4) 3 d of refeeding with no Cu and Zn supplement, and 5) 4 d of Cu and Zn repletion. Calves fed CuLys had 53% greater apparent Cu absorption and increased Cu retention (P < .05) during repletion compared with calves fed CuSO4. The 18-d mean retention of Cu from CuLys was greater (P < .05) than that from CuSO4. No differences (P > .05) in apparent absorption or retention of Zn were found between Zn sources, although during the 18-d trial mean retention was 58% higher when ZnMet was fed. Urinary Cu and Zn excretion decreased (P < .01) during stress.(ABSTRACT TRUNCATED AT 250 WORDS)

Zinc affects the metabolism of thyroid hormones in children with Down's syndrome: normalization of thyroid stimulating hormone and of reversal triiodothyronine plasmic levels by dietary zinc supplementation.

Levels of circulating thyroid stimulating hormone (TSH), tetraiodothyronine (T4), 3,5,3'-triiodothyronine (T3), and 3,3',5' triiodothyronine (reversal T3 or rT3) were measured in 25 children with trisomy of chromosome 21, also known as Down's syndrome (DS), and in 14 normal children. In subjects with DS TSH levels were increased, while plasmic levels of rT3 were decreased. No alteration in T3 and T4 levels was observed. Before zinc supplementation, plasmic levels of zinc and thymulin, a zinc dependent thymic hormone, were significantly decreased in DS children. After four months of dietary supplementation with zinc sulphate, a normalization of plasmic zinc, thymulin and TSH levels was observed. Plasmic levels of rT3 significantly increased, and after zinc treatment no difference was detectable between DS children and normal children. Clinical evaluation of the health status of DS children showed that zinc supplementation decreased the incidence of infectious diseases and improved school attendance. Thus, the increased efficiency of the immune system and the normalization of some endocrine parameters by zinc supplementation suggests that zinc deficiency may play a crucial role in some of the pathological manifestations associated with the syndrome, such as infections and malfunctioning of the thyroid gland.