BioMetals (v.24, #5)

Lactoferrin (LF) is an iron-binding glycoprotein of the transferrin family, today known to have multifunctional physiological activities. In humans, under normal conditions, LF has been found in blood, mucosal secretions, gastrointestinal fluids, urine and mostly in milk and colostrum. The first pioneering immunohistochemical report about LF distribution in human tissues dated in 1978; successively, many studies have been performed to analyze the LF immunohistochemical pattern in different normal and neoplastic tissues. In this review, we present data from literature concerning the evidence of LF in tumors together with those by us obtained during more than 25 years; the immunohistochemical applications to human neoplastic tissues have been done to investigate the LF pathogenetic role as well as its activity in cancer. After a systematic analysis of LF immunoreactivity in different human districts, a possible explanation for its presence and function has been modulated for each site or tissue, according to experimental evidences obtained either by in vivo as well as by in vitro studies.
Keywords: Lactoferrin; Cancer; Immunohistochemistry; Research; Clinical applications

Transition metal homeostasis: from yeast to human disease by Mark R. Bleackley; Ross T. A. MacGillivray (785-809).
Transition metal ions are essential nutrients to all forms of life. Iron, copper, zinc, manganese, cobalt and nickel all have unique chemical and physical properties that make them attractive molecules for use in biological systems. Many of these same properties that allow these metals to provide essential biochemical activities and structural motifs to a multitude of proteins including enzymes and other cellular constituents also lead to a potential for cytotoxicity. Organisms have been required to evolve a number of systems for the efficient uptake, intracellular transport, protein loading and storage of metal ions to ensure that the needs of the cells can be met while minimizing the associated toxic effects. Disruptions in the cellular systems for handling transition metals are observed as a number of diseases ranging from hemochromatosis and anemias to neurodegenerative disorders including Alzheimer’s and Parkinson’s disease. The yeast Saccharomyces cerevisiae has proved useful as a model organism for the investigation of these processes and many of the genes and biological systems that function in yeast metal homeostasis are conserved throughout eukaryotes to humans. This review focuses on the biological roles of iron, copper, zinc, manganese, nickel and cobalt, the homeostatic mechanisms that function in S. cerevisiae and the human diseases in which these metals have been implicated.
Keywords: Iron; Zinc; Copper; Manganese; Cobalt; Nickel; Transition metal homeostasis; Saccharomyces cerevisiae; Human disease

Manganese accumulation in the CNS and associated pathologies by Susana Rivera-Mancía; Camilo Ríos; Sergio Montes (811-825).
Manganese (Mn) is an essential metal for life. It is a key constituent of clue enzymes in the central nervous system, contributing to antioxidant defenses, energetic metabolism, ammonia detoxification, among other important functions. Until now, Mn transport mechanisms are partially understood; however, it is known that it shares some mechanisms of transport with iron. CNS is susceptible to Mn toxicity because it possesses mechanisms that allow Mn entry and favor its accumulation. Cases of occupational Mn exposure have been extensively reported in the literature; however, there are other ways of exposure, such as long-term parental nutrition and liver failure. Manganism and hepatic encephalopathy are the most common pathologies associated with the effects of Mn exposure. Both pathologies are associated with motor and psychiatric disturbances, related in turn to mechanisms of damage such as oxidative stress and neurotransmitters alterations, the dopaminergic system being one of the most affected. Although manganism and Parkinson’s disease share some characteristics, they differ in many aspects that are discussed here. The mechanisms for Mn transport and its participation in manganism and hepatic encephalopathy are also considered in this review. It is necessary to find an effective therapeutic strategy to decrease Mn levels in exposed individuals and to treat Mn long term effects. In the case of patients with chronic liver failure it would be worthwhile to test a low-Mn diet in order to ameliorate symptoms of hepatic encephalopathy possibly related to Mn accumulation.
Keywords: Manganese transport; Dopamine; Manganism; Hepatic encephalopathy; Oxidative stress

Cu(II)-reduction by Escherichia coli cells is dependent on respiratory chain components by Sabrina I. Volentini; Ricardo N. Farías; Luisa Rodríguez-Montelongo; Viviana A. Rapisarda (827-835).
Copper is both an essential nutrient and a toxic element able to catalyze free radicals formation which damage lipids and proteins. Although the available copper redox species in aerobic environment is Cu(II), proteins that participate in metal homeostasis use Cu(I). With isolated Escherichia coli membranes, we have previously shown that electron flow through the respiratory chain promotes cupric ions reduction by NADH dehydrogenase-2 and quinones. Here, we determined Cu(II)-reductase activity by whole cells using strains deficient in these respiratory chain components. Measurements were done by the appearance of Cu(I) in the supernatants of cells exposed to sub-lethal Cu(II) concentrations. In the absence of quinones, the Cu(II)-reduction rate decreased ~70% in respect to the wild-type strain, while this diminution was about 85% in a strain lacking both NDH-2 and quinones. The decrease was ~10% in the absence of only NDH-2. In addition, we observed that quinone deficient strains failed to grow in media containing either excess or deficiency of copper, as we have described for NDH-2 deficient mutants. Thus, the Cu(II)-reduction by E. coli intact cells is mainly due to quinones and to a lesser extent to NDH-2, in a quinone-independent way. To our knowledge, this is the first in vivo demonstration of the involvement of E. coli respiratory components in the Cu(II)-reductase activity which contributes to the metal homeostasis.
Keywords: Cupric ion reduction; Quinones; NADH dehydrogenase-2

Uranium, thorium and rare earth elements in macrofungi: what are the genuine concentrations? by Jan Borovička; Jaroslava Kubrová; Jan Rohovec; Zdeněk Řanda; Colin E. Dunn (837-845).
Concentrations of uranium, thorium and rare earth elements (REE) in 36 species of ectomycorrhizal (26 samples) and saprobic (25 samples) macrofungi from unpolluted sites with differing bedrock geochemistry were analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Analytical results are supported by use of certified reference materials (BCR-670, BCR-667, NIST-1575a) and the reliability of the determination of uranium was verified by epithermal neutron activation analysis (ENAA). It appears that data recently published on these elements are erroneous, in part because of use of an inappropriate analytical method; and in part because of apparent contamination by soil particles resulting in elevated levels of thorium and REE. Macrofungi from unpolluted areas, in general, did not accumulate high levels of the investigated metals. Concentrations of uranium and thorium were generally below 30 and 125 μg kg−1 (dry weight), respectively. Concentrations of REE in macrofungi did not exceed 360 μg kg−1 (dry weight) and their distribution more or less followed the trend observed in post-Archean shales and loess.
Keywords: ICP-MS; ENAA; REE; Fungi; Bioaccumulation; Metals

Bovine milk lactoferrin induces synthesis of the angiogenic factors VEGF and FGF2 in osteoblasts via the p44/p42 MAP kinase pathway by Kei-ichi Nakajima; Yosuke Kanno; Masato Nakamura; Xiao-Dong Gao; Asami Kawamura; Fumiaki Itoh; Akira Ishisaki (847-856).
Lactoferrin (LF) belongs to the transferrin family and is present in several physiological fluids, including milk and colostrum. LF has recently been identified as an anabolic factor for bone. Here we investigated whether bovine LF (bLF) induces synthesis of angiogenic factors by osteoblasts. If so, we examined the underlying mechanism. We found that bLF purified from milk increased the mRNA expression of vascular endothelial growth factor (VEGF) and fibroblast growth factor-2 (FGF2) in murine osteoblast-like MC3T3-E1 cells and primary murine osteoblasts in a time- and dose-dependent manner. Furthermore, bLF increased VEGF and FGF2 protein levels in MC3T3-E1 cells. In addition, treatment of MC3T3-E1 cells with bLF rapidly induced phosphorylation of p44/p42 mitogen-activated protein (MAP) kinase. The bLF-mediated increases in VEGF and FGF2 mRNA and protein were inhibited by U0126, a specific inhibitor of the upstream kinase that activates p44/p42 MAP kinase (MEK). Taken together, our results strongly suggest that bLF induces VEGF and FGF2 synthesis in a p44/p42 MAP kinase-dependent manner in MC3T3-E1 cells.
Keywords: FGF2; Lactoferrin; Osteoblasts; p44/p42 MAP kinase; VEGF

Characterization of basolateral-to-apical transepithelial transport of cadmium in intestinal TC7 cell monolayers by Pascale Carrière; Marc Mantha; Sophie Champagne-Paradis; Catherine Jumarie (857-874).
Cadmium (Cd) is a toxic metal with an extremely long half-life in humans. The intestinal absorption of Cd has been extensively studied but the role the intestinal epithelium may play in metal excretion has never been considered. The basolateral (BL)-to-apical (AP) transepithelial transport of Cd was characterized in TC7 human intestinal cells. Both AP and BL uptakes varied with days in culture, and BL uptake was twofold higher compared to AP in differentiated cultures. A 50% increase in the BL uptake of 0.5 μM 109Cd was observed at pH 8.5 in a chloride but not nitrate medium, suggesting the involvement of a pH-sensitive mechanism of transport for chloro-complexes. Fe and Zn inhibited the BL uptake of Cd whereas complexation by albumin had no effect, but the stimulatory effect of pH 8.5 was lost in the presence of albumin. The BL uptake of [3H]-MPP+ and 109Cd were both inhibited by decynium22 without reciprocal inhibition. MRP2 and MDR1 mRNA levels increased as a function of days in culture. A 25 and 20% decrease in the cellular AP efflux of Cd was observed in the presence of verapamil and probenecid, respectively. In cells treated with BSO, which lowered by 26% the total cellular thiol content, the inhibitory effect of verapamil increased, whereas that of probenecid decreased. These results reveal the existence of a decynium22-sensitive mechanism of transport for Cd at the BL membrane, and suggest the involvement of MDR1 and MRP2 in cellular Cd efflux at the AP membrane. It is conceivable that the intestinal epithelium may contribute to Cd blood excretion.
Keywords: Cadmium; Basolateral membrane; OCT; MRP2; MDR1; TC7 intestinal cells; Metal speciation

Zinc ion homeostasis plays an important role in human cutaneous biology where it is involved in epidermal differentiation and barrier function, inflammatory and antimicrobial regulation, and wound healing. Zinc-based compounds designed for topical delivery therefore represent an important class of cutaneous therapeutics. Zinc pyrithione (ZnPT) is an FDA-approved microbicidal agent used worldwide in over-the-counter topical antimicrobials, and has also been examined as an investigational therapeutic targeting psoriasis and UVB-induced epidermal hyperplasia. Recently, we have demonstrated that cultured primary human skin keratinocytes display an exquisite sensitivity to nanomolar ZnPT concentrations causing induction of heat shock response gene expression and poly(ADP-ribose) polymerase (PARP)-dependent cell death (Cell Stress Chaperones 15:309–322, 2010). Here we demonstrate that ZnPT causes rapid accumulation of intracellular zinc in primary keratinocytes as observed by quantitative fluorescence microscopy and inductively coupled plasma mass spectrometry (ICP-MS), and that PARP activation, energy crisis, and genomic impairment are all antagonized by zinc chelation. In epidermal reconstructs (EpiDerm™) exposed to topical ZnPT (0.1–2% in Vanicream™), ICP-MS demonstrated rapid zinc accumulation, and expression array analysis demonstrated upregulation of stress response genes encoding metallothionein-2A (MT2A), heat shock proteins (HSPA6, HSPA1A, HSPB5, HSPA1L, DNAJA1, HSPH1, HSPD1, HSPE1), antioxidants (SOD2, GSTM3, HMOX1), and the cell cycle inhibitor p21 (CDKN1A). IHC analysis of ZnPT-treated EpiDerm™ confirmed upregulation of Hsp70 and TUNEL-positivity. Taken together our data demonstrate that ZnPT impairs zinc ion homeostasis and upregulates stress response gene expression in primary keratinocytes and reconstructed human epidermis, activities that may underlie therapeutic and toxicological effects of this topical drug.
Keywords: Zinc pyrithione; Keratinocyte; Reconstructed epidermis; Heat shock response; HSPA1A; ICP-MS

Nitrate reduction associated with respiration in Sinorhizobium meliloti 2011 is performed by a membrane-bound molybdoenzyme by Felix M. Ferroni; María G. Rivas; Alberto C. Rizzi; María E. Lucca; Nora I. Perotti; Carlos D. Brondino (891-902).
The purification and biochemical characterization of the respiratory membrane-bound nitrate reductase from Sinorhizobium meliloti 2011 (Sm NR) is reported together with the optimal conditions for cell growth and enzyme production. The best biomass yield was obtained under aerobic conditions in a fed-batch system using Luria–Bertani medium with glucose as carbon source. The highest level of Sm NR production was achieved using microaerobic conditions with the medium supplemented with both nitrate and nitrite. Sm NR is a mononuclear Mo-protein belonging to the DMSO reductase family isolated as a heterodimeric enzyme containing two subunits of 118 and 45 kDa. Protein characterization by mass spectrometry showed homology with respiratory nitrate reductases. UV–Vis spectra of as-isolated and dithionite reduced Sm NR showed characteristic absorption bands of iron-sulfur and heme centers. Kinetic studies indicate that Sm NR follows a Michaelis–Menten mechanism (K m = 97 ± 11 μM, V = 9.4 ± 0.5 μM min−1, and k cat = 12.1 ± 0.6 s−1) and is inhibited by azide, chlorate, and cyanide with mixed inhibition patterns. Physiological and kinetic studies indicate that molybdenum is essential for NR activity and that replacement of this metal for tungsten inhibits the enzyme. Although no narGHI gene cluster has been annotated in the genome of rhizobia, the biochemical characterization indicates that Sm NR is a Mo-containing NR enzyme with molecular organization similar to NarGHI.
Keywords: Sinorhizobium meliloti ; Membrane-bound nitrate reductase; Nitrogen metabolism; Kinetic studies

Some characteristics of membrane Cd2+ transport in rat thymocytes: an analysis using Fluo-3 by Takuya Kawanai; Masahiro Fujinaga; Kazuki Koizumi; Isao Kurotani; Erika Hashimoto; Masaya Satoh; Shoji Imai; Norikazu Miyoshi; Yasuo Oyama (903-914).
Although cadmium-induced apoptosis of lymphocytes is one of common features in the immunotoxicity of cadmium, the membrane pathway for intracellular cadmium accumulation is not fully elucidated. To characterize membrane Cd2+ transport of rat thymocytes, the change in intracellular Cd2+ concentration under various conditions was examined by the use of Fluo-3, a fluorescent probe for monitoring the change in intracellular concentration of divalent metal cations. The membrane Cd2+ transport was estimated by the augmentation of Fluo-3 fluorescence induced by bath application of CdCl2. Lowering temperature strongly suppressed the augmentation of Fluo-3 fluorescence by CdCl2, suggesting that the metabolic process can be involved in membrane Cd2+ transport. External acidification (decreasing pH) and membrane depolarization by adding KCl attenuated the augmentation, indicating the requirement of electrochemical driving force for membrane Cd2+ transport into the cells. Bath application of CaCl2 and ZnCl2 equally decreased the augmentation, suggesting their competition with Cd2+ at the membrane transport. The augmentation by CdCl2 was lesser in the cells treated with N-ethylmaleimide inducing chemical depletion of cellular thiols. The result suggests the contribution of sulfhydryl groups to membrane Cd2+ transport. Taken together, it is suggested that the cells possess a temperature-sensitive membrane Cd2+ pathway, driven by electrochemical gradient of Cd2+ and transmembrane potential, with competitive binding site. Based on the characteristics described above, it is unlikely that the membrane Cd2+ transport in rat thymocytes is attributed to a single transport system although it has characteristics that are similar to those of divalent cation transporter 1.
Keywords: Cadmium; Membrane; Transport; Flow cytometer; Fluo-3

Spectroscopic studies of amphotericin B–Cu2+ complexes by Mariusz Gagoś; Grzegorz Czernel; Daniel M. Kamiński; Krzysztof Kostro (915-922).
The aim of this research is to investigate amphotericin B (AmB)–Cu2+ complexes in aqueous solution at different pH values. Electronic absorption, circular dichroism (CD), Raman and FTIR spectroscopies were used in this study. We found that different concentrations of AmB and Cu2+ ions in solution leads to formation of complexes with stoichiometry of 2:1 and 1:1. The formation of AmB–Cu2+ complexes at physiological pH values is accompanied by changes of the molecular organization of AmB especially disaggregation. These observed effects might be significant from a medical point of view.
Keywords: Amphotericin B; Copper complexes; pH; Electronic absorption; CD, Raman and FTIR spectroscopies

Antifungal activity of α-methyl trans cinnamaldehyde, its ligand and metal complexes: promising growth and ergosterol inhibitors by Sheikh Shreaz; Rayees A. Sheikh; Rimple Bhatia; Khan Neelofar; Sheikh Imran; Athar A. Hashmi; Nikhat Manzoor; Seemi F. Basir; Luqman A. Khan (923-933).
Antifungal effectivity and utility of cinnamaldehyde is limited because of its high MIC and skin sensitivity. In this study, α-methyl trans cinnamaldehyde, a less irritating derivative, have been self coupled and complexed with Co(II) and Ni(II) to generate N, N′–Bis (α-methyl trans cinnamadehyde) ethylenediimine [C22H24N2], [Co(C44H48N4)Cl2] and [Ni(C44H48N4)Cl2]. Ligand and complexes were characterized on the basis of FTIR, ESI–MS, IR and 1HNMR techniques. Synthesized ligand [L] and complexes were investigated for their MICs, inhibition of ergosterol biosynthesis and H+ extrusion against three strains of Candida: C. albicans 44829, C. tropicalis 750 and C. krusei 6258. Average of three species MIC of methyl cinnamaldehyde is 317 μg/ml (2168 μM). Compared to methyl cinnamaldehyde ligand [L], Co(II) and Ni(II) complex are found to be 4.48, 17.78 and 21.46 times more effective in liquid medium and 2.73, 8.93 and 10.38 times more effective in solid medium. At their respective MIC90 average inhibition of ergosterol biosynthesis caused by methyl cinnamaldehyde, ligand [L], Co(II) and Ni(II) complex, respectively was 80, 78, 90 and 93%. H+ extrusion was also significantly inhibited but did not co-relate well with MIC90. Results indicate ergosterol biosynthesis as site of action of α-methyl cinnamaldehyde, synthesized ligand and complexes. α-methyl cinnamaldehyde and ligand did not show any toxicity against H9c2 rat cardiac myoblast cell, whereas Co(II) and Ni(II) complexes on an average produced 19% cellular toxicity.
Keywords: Candida; α-methyl trans cinnamaldehyde; Metal complexes; PM-ATPase; Ergosterol

Metallic ion content and damage to the DNA in oral mucosa cells of children with fixed orthodontic appliances by Esther Fernández-Miñano; Clara Ortiz; Ascensión Vicente; José L. Calvo; Antonio J. Ortiz (935-941).
Although the metal devices used in orthodontic treatments are manufactured highly resistance to corrosion, they may still suffer some localized corrosion resulting from the oral cavity conditions. The corrosion causes the release of metals from the alloys used for their manufacture. In this report, we evaluated the in vivo metal ions release of three alloys (stainless steel, titanium and nickel-free) usually used in the orthodontics treatments and its genotoxicity. We applied to 15 patients, between 12 and 16 years, 4 tubes and 20 brackets. Samples from oral mucosa were taken before the treatment and 30 days later. The concentration of the titanium, chromium, manganese, cobalt, nickel, molybdenum and iron were detected using inductively coupled plasma mass spectrometry (ICP-MS). The genotoxicity was measured with a comet assay (Olive moment). The oral mucosa cells in contact with the stainless steel alloy displayed the greatest titanium and manganese concentrations and those in contact with the nickel-free alloy presented the greatest concentration of chromium and iron. Both alloys, stainless steel and nickel-free, induced a higher DNA damage in the oral mucosa cells than the titanium alloy, in which the Olive moment was similar to controls. Based on the results of our study, we can conclude that titanium brackets and tubes are the most biocompatible of the three alloys.
Keywords: Orthodontic alloy; Metal toxicity; ICP-MS; DNA damage; Comet assay

Influence of vanadium supplementation on oxidative stress factors in the muscle of STZ-diabetic rats by Ozlem Kurt; Tugba Yilmaz Ozden; Nurten Ozsoy; Sevim Tunali; Ayse Can; Nuriye Akev; Refiye Yanardag (943-949).
In recent years, the role of free radical damage consequent to oxidative stress is widely discussed in diabetic complications. In this aspect, the protection of cell integrity by trace elements is a topic to be investigated. Vanadium is a trace element believed to be important for normal cell function and development. The aim of the present study was to investigate the effect of vanadyl sulfate supplementation on the antioxidant system in the muscle tissue of diabetic rats. Diabetes was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg body weight) to male Swiss albino rats. The rats were randomly divided into 4 groups: Group I, control; Group II, vanadyl sulfate control; Group III, STZ-diabetic untreated; Group IV, STZ-diabetic treated with vanadyl sulfate. Vanadyl sulfate (100 mg/kg) was given daily by gavage for 60 days. At the last day of the experiment, rats were killed, muscle tissues were taken, homogenized in cold saline to make a 10% (w/v) homogenate. Body weights and blood glucose levels were estimated at 0, 30 and 60th days. Antioxidant enzymes, superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx), glutathione-S-transferase (GST), as well as carbonic anhydrase (CA), myeloperoxidase (MPO) activities and protein carbonyl content (PCC) were determined in muscle tissue. Vanadyl sulfate administration improved the loss in body weight due to STZ-induced diabetes and decreased the rise in blood glucose levels. It was shown that vanadium supplementation to diabetic rats significantly decrease serum antioxidant enzyme levels, which were significantly raised by diabetes in muscle tissue showing that this trace element could be used as preventive for diabetic complications.
Keywords: Vanadium; Antioxidant enzymes; Muscle; Diabetes mellitus; Streptozotocin

Induction of oxidative stress by low doses of lead in human hepatic cell line WRL-68 by Pablo Hernández-Franco; Martín Silva; Mahara Valverde; Emilio Rojas (951-958).
Even though the molecular mechanisms by which lead induces toxicity and cancer have been intensely studied for many years, its carcinogenic mechanisms are not well understood yet. Several possible mechanisms have been examined to gain understanding on the carcinogenic properties of lead, which include mitogenesis, alteration of gene expression, and oxidative damage, among others. The aim of the present study was to explore the induction of oxidative damage at low lead concentrations using human embryonic hepatic cells WRL-68. Our results showed induction of reactive oxygen species, changes in the superoxide dismutase and catalase activity, as well as an induction of lipidperoxidation and DNA damage. However, after 5 weeks of exposure, these alterations returned to their basal levels. These results taking together indicate that at low concentrations, lead is able to establish an oxidative stress scenario; however under optimal antioxidant defense the oxidative scenario could be abolished through an adaptative process.
Keywords: Lead; Oxidative stress; Catalase; SOD; ROS; DNA damage; Lipid peroxidation

Zinc alleviates mercury-induced oxidative stress in Pfaffia glomerata (Spreng.) Pedersen by Nicéia Spanholi Calgaroto; Denise Cargnelutti; Liana Veronica Rossato; Júlia Gomes Farias; Sibila Trojahn Nunes; Luciane Almeri Tabaldi; Fabiane Goldschmidt Antes; Erico Marlon Moraes Flores; Maria Rosa Chitolina Schetinger; Fernando Teixeira Nicoloso (959-971).
The possible role of zinc (Zn) to reverse the oxidative stress caused by mercury (Hg) was investigated in Pfaffia glomerata plantlets. Thirty-day-old acclimatized plantlets of P. glomerata were exposed to four treatments: control, 50 μM Zn, 50 μM Hg and 50 μM Zn + 50 μM Hg for 9 days. In Zn + Hg treatment, shoot and root Hg concentrations were 59 and 24% smaller than that plants exposed to 50 μM Hg added alone. An increase in the Zn concentration in the shoot of plants exposed to Zn + Hg occurred, although in the roots Zn concentration was not altered, when compared to the control. Fresh and dry weights, as well as the activity of δ-aminolevulinic acid dehydratase (δ-ALA-D) in Hg-treated plants were significantly reduced. Percentage survival, fresh and dry weights and δ-ALA-D activity of plants treated by 50 μM Zn + 50 μM Hg were greater than of that treated by Hg alone. Moreover, Zn treatment reduced the lipid peroxidation caused by Hg, being this effect related to increased root superoxide dismutase activity, and shoot catalase and ascorbate peroxidase activities. In conclusion, the presence of Zn in the substrate caused a significant reduction in the oxidative stress induced by Hg.
Keywords: Antioxidant system; Brazilian ginseng; Mercury; Oxidative stress; Pfaffia glomerata ; Zinc

Effects of aluminum exposure on the allergic responses and humoral immune function in rats by Yanzhu Zhu; Jinfeng Xu; Hao Sun; Chongwei Hu; Hansong Zhao; Bing Shao; Alphajoh A. Bah; Yanfei Li (973-977).
This study was conducted to assess effects of aluminum (Al) exposure on allergic responsive reactions and humoral immune function in rats. Forty male Wistar rats (5 weeks old) weighed 110–120 g were randomly allocated into four groups and were orally exposed to 0, 64.18, 128.36, and 256.72 mg/kg body weight aluminum trichloride in drinking water for 120 days. The levels of immunoglobulin (Ig) G, IgA, IgM, IgE, Complement factor (C)3, and C4 in serum were determined by ELISA and nephelometric assays at the end of experiment. The results showed that the levels of IgM, C3, and C4 were lowered, and the levels of IgG, IgA, and IgE were increased in an Al-dose dependent manner. The increased in IgE level and the decreased in C3 and C4 levels indicate that Al induces allergic responses in rats; while the increased levels in IgG and IgA and the decreased level in IgM suggest that Al disorders the humoral immune function in rats.
Keywords: Aluminum exposure; Allergic responses; Humoral immune function; Rats

Erratum to: Effects of aluminum exposure on the allergic responses and humoral immune function in rats by Yanzhu Zhu; Jinfeng Xu; Hao Sun; Chongwei Hu; Hansong Zhao; Bing Shao; Alphajoh A. Bah; Yanfei Li (979-979).