Novel oral detoxification of mercury, cadmium, and lead with thiol-modified nanoporous silica.
ABSTRACT: We have developed a thiol-modified nanoporous silica material (SH-SAMMS) as an oral therapy for the prevention and treatment of heavy metal poisoning. SH-SAMMS has been reported to be highly efficient at capturing heavy metals in biological fluids and water. Herein, SH-SAMMS was examined for efficacy and safety in both in vitro and in vivo animal models for the oral detoxification of heavy metals. In simulated gastrointestinal fluids, SH-SAMMS had a very high affinity (Kd) for methyl mercury (MeHg(I)), inorganic mercury (Hg(II)), lead (Pb(II)), and cadmium (Cd(II)) and was superior to other SAMMS with carboxylic acid or phosphonic acid ligands or commercially available metal chelating sorbents. SH-SAMMS also effectively removed Hg from biologically digested fish tissue with no effect on most nutritional minerals found in fish. SH-SAMMS could hold Hg(II) and MeHg(I) tightly inside the nanosize pores, thus preventing bacteria from converting them to more absorbable forms. Rats fed a diet containing MeHg(I), Cd(II), and Pb(II) and SH-SAMMS for 2 weeks had blood Hg levels significantly lower than rats fed the metal-rich diet only. Upon cessation of the metal-rich diet, continued administration of SH-SAMMS for 2 weeks facilitated faster and more extensive clearance of Hg than in animals not continued on oral SH-SAMMS. Rats receiving SH-SAMMS also suffered less weight loss as a result of the metal exposure. Retention of Hg and Cd in major organs was lowest in rats fed with SH-SAMMS throughout the entire four weeks. The reduction of blood Pb by SH-SAMMS was significant. SH-SAMMS was safe to intestinal epithelium model (Caco-2) and common intestinal bacteria (Escherichia coli). Altogether, it has great potential as a new oral drug for the treatment of heavy metal poisoning. This new application is enabled by the installation of tailored interfacial chemistry upon nontoxic nanoporous materials.
Project description:Cupriavidus metallidurans CH34 is a metal resistant beta-proteobacterium. The genome of this bacterium contain many genes involved in heavy metal resistance. Gene expression of C. metallidurans was studied after the addition of of Zn(II), Cd(II), Cu(II), Ni(II), Pb(II), Hg(II) or Co(II). Keywords: Heavy metal stress response Overall design: Cultures of C. metallidurans CH34 were grown at 30°C until OD reached 0.6 (mid- exponential phase cultures). Heavy metals (0.8 mM of Zn(II), 0.5 mM of Cd(II), 0.1 mM of Cu(II), 0.6 mM of Ni(II), 0.4 mM of Pb(II), 5 uM of Hg(II) and 0.5 mM of Co(II)) were added to the culture for 30 minutes induction time. Total RNA was extracted, reverse-transcribed and labeled with Cy3-dCTP for the control (without metal) and with Cy5-dCTP for each conditions (challenged with one metal). Labeled cDNA were (control and one condition) added to a spotted slide for overnight hybridization at 42°C. Slides were scanned with a laser at 532 and 635 nm.
Project description:Cupriavidus metallidurans CH34 is a metal resistant beta-proteobacterium. The genome of this bacterium contain many genes involved in heavy metal resistance. Gene expression of C. metallidurans was studied after the addition of of Zn(II), Cd(II), Cu(II), Ni(II), Pb(II), Hg(II) or Co(II). Keywords: Heavy metal stress response Cultures of C. metallidurans CH34 were grown at 30°C until OD reached 0.6 (mid- exponential phase cultures). Heavy metals (0.8 mM of Zn(II), 0.5 mM of Cd(II), 0.1 mM of Cu(II), 0.6 mM of Ni(II), 0.4 mM of Pb(II), 5 uM of Hg(II) and 0.5 mM of Co(II)) were added to the culture for 30 minutes induction time. Total RNA was extracted, reverse-transcribed and labeled with Cy3-dCTP for the control (without metal) and with Cy5-dCTP for each conditions (challenged with one metal). Labeled cDNA were (control and one condition) added to a spotted slide for overnight hybridization at 42°C. Slides were scanned with a laser at 532 and 635 nm.
Project description:Background: The objective of this study was to compare the levels of heavy metals (Pb, Hg, and Cd) and metallothionein (MT) in the gills and stomach of two species of mussels ( Crassostrea iredalei and Crassostrea glomerata), and to observe the ability of the mussels to absorb the heavy metals Pb, Hg and Cd present in the water. Methods: The mussels were obtained from Mayangan, Kenjeran and Gresik ports, East Java, Indonesia. MT levels were determined using ELISA. Heavy metal levels of Pb, Hg and Cd were assayed using atomic absorption spectrophotometry. Results: The levels of Pb and Cd in water were below the maximum permissible levels for local water quality standards. By contrast, the level of Hg in the water was above the maximum permissible levels for water quality standards. At Mayangan Port (Station 1), the level of Pb was higher than Hg and Cd. Levels of MT and heavy metals varied greatly among of C. iredalei and C. glomerata individuals, but were always higher in the gills than in the stomach. The highest MT level (160,250 ng/g) was observed at Kenjeran Port (Station 2). MT levels were shown to be significantly associated with heavy metal level ( P<0.0001). Conclusions: This result indicates that MT may be responsible for the sequestration of these heavy metals, as has already been observed in terrestrial animals.
Project description:Shark meat is consumed as a food source worldwide, especially in Asian countries. However, since sharks are apex predators in the ocean food chain, they are prone to bioaccumulation of heavy metals. More than 100 million sharks are caught annually for human consumption, and the safety of shark meat cannot be overemphasized. Here, we examined heavy metal concentration in the muscle tissue of 6 shark species including 3 migratory species (Carcharhinus brachyurus, Carcharhinus obscurus, and Isurus oxyrinchus) and 3 local species (Triakis scyllium, Mustelus manazo, and Cephaloscyllium umbratile) from fish markets in Jeju Island, Republic of Korea. The concentrations of 11 heavy metals (Cr, Fe, Cu, Zn, As, Se, Cd, Sn, Sb, Pb, and Hg) and MeHg were analyzed. The result showed that the average concentrations of all metals, except for that of As, were below the regulatory maximum limits of many organizations, including the Codex standard. Hg and MeHg were significantly correlated with body length, body weight, and age, and the concentration of Hg was expected to exceed the limit in C. brachyurus with a body length or weight of over 130 cm or 25 kg, respectively. Our results indicate that shark meat can expose consumers to a high level of As and that copper sharks bigger than the predicted size should be avoided for excessive Hg. Considering these findings, a detailed guideline on consumption of meat of different shark species should be suggested based on further investigation.
Project description:Members of the ArsR/SmtB family of transcriptional repressors, such as CadC, regulate the intracellular levels of heavy metals like Cd(II), Hg(II), and Pb(II). These metal sensing proteins bind their target metals with high specificity and affinity, however, a lack of structural information about these proteins makes defining the coordination sphere of the target metal difficult. Lingering questions as to the identity of Cd(II) coordination in CadC are addressed via protein design techniques. Two designed peptides with tetrathiolate metal binding sites were prepared and characterized, revealing fast exchange between CdS3O and CdS4 coordination spheres. Correlation of (111m)Cd PAC spectroscopy and (113)Cd NMR spectroscopy suggests that Cd(II) coordinated to CadC is in fast exchange between CdS3O and CdS4 forms, which may provide a mechanism for rapid sensing of heavy metal contaminants by this regulatory protein.
Project description:Metal homeostasis and resistance in bacteria is maintained by a panel of metal-sensing transcriptional regulators that collectively control transition metal availability and mediate resistance to heavy metal xenobiotics, including As(III), Cd(II), Pb(II), and Hg(II). The ArsR family constitutes a superfamily of metal sensors that appear to conform to the same winged helical, homodimeric fold, that collectively "sense" a wide array of beneficial metal ions and heavy metal pollutants. The genomes of many actinomycetes, including the soil dwelling bacterium Streptomyces coelicolor and the human pathogen Mycobacterium tuberculosis, encode over ten ArsR family regulators, most of unknown function. Here, we present the characterization of a homologue of M. tuberculosis CmtR (CmtR(Mtb)) from S. coelicolor, denoted CmtR(Sc). We show that CmtR(Sc), in contrast to CmtR(Mtb), binds two monomer mol equivalents of Pb(II) or Cd(II) to form two pairs of sulfur-rich coordination complexes per dimer. Metal site 1 conforms exactly to the alpha4C site previously characterized in CmtR(Mtb) while metal site 2 is coordinated by a C-terminal vicinal thiolate pair, Cys110 and Cys111. Biological assays reveal that only Cd(II) and, to a lesser extent, Pb(II) mediate transcriptional derepression in the heterologous host Mycobacterium smegmatis in a way that requires metal site 1. In contrast, mutagenesis of metal site 2 ligands Cys110 or Cys111 significantly reduces Cd(II) responsiveness, with no detectable effect on Pb(II) sensing. The implications of these findings on the ability to predict metal specificity and function from metal-site signatures in the primary structure of ArsR family proteins are discussed.
Project description:In this study, we investigate the adsorption capability of molybdenum sulfide (MoS2)/thiol-functionalized multiwalled carbon nanotube (SH-MWCNT) nanocomposite for rapid and efficient removal of heavy metals [Pb(II) and Cd(II)] from industrial mine water. The MoS2/SH-MWCNT nanocomposite was synthesized by acid treatment and sulfurization of MWCNTs followed by a facile hydrothermal reaction technique using sodium molybdate and diethyldithiocarbamate as MoS2 precursors. Morphological and chemical features of the nanocomposite material were studied using various characterization techniques. Furthermore, the effects of adsorbent (MoS2/SH-MWCNT nanocomposite) concentration, contact time, initial concentration of heavy-metal ions, and reaction temperature were examined to determine the efficiency of the adsorption process in batch adsorption experiments. Kinetics and isotherm studies showed that the adsorption process followed pseudo-second-order and Freundlich adsorption isotherm models, respectively. Thermodynamic parameters calculated using van't Hoff plots show the spontaneity and endothermic nature of adsorption. MoS2/SH-MWCNT nanocomposite demonstrates a high adsorption capacity for Pb(II) (90.0 mg g-1) and Cd(II) (66.6 mg g-1) following ion-exchange and electrostatic interactions. Metal-sulfur complex formation was identified as the key contributor for adsorption of heavy-metal ions followed by electrostatic interactions for multilayer adsorption. Transformation of adsorbent into PbMoO4-x S x and CdMoO4-x S x complex because of the adsorption process was confirmed by X-ray diffraction and scanning electron microscopy-energy-dispersive spectrometry. The spent adsorbent can further be used for photocatalytic and electrochemical applications; therefore, the generated secondary byproducts can also be employed for other purposes.
Project description:Few studies have examined the relationship between the amounts of heavy metal and stroke incidence. The aim of this study was to explore the relationship between levels of heavy metals, including Pb, Hg, As, and Cd, in patients with acute ischemic stroke (AIS).We selected patients with first-ever AIS onset within 1 week as our study group. Healthy controls were participants without a history of stroke or chronic disease, except hypertension. The serum levels of Pb, Hg, As, and Cd in participants in the experimental and control groups were determined. All participants received a 1-g infusion of edetate calcium disodium (EDTA). Urine specimens were collected for 24 h after EDTA infusion and measured for heavy metal levels.In total, 33 patients with AIS and 39 healthy controls were enrolled in this study. The major findings were as follows: (1) The stroke group had a significantly lower level of serum Hg (6.4?±?4.3 ?g/L vs. 9.8?±?7.0 ?g/L, P =?0.032, OR?=?0.90, 95% CI?=?0.81-0.99) and a lower level of urine Hg (0.7?±?0.7 ?g/L vs. 1.2?±?0.6 ?g/L, P =?0.006, OR?=?0.27, 95% CI?=?0.11-0.68) than the control group. (2) No significant difference in serum Pb (S-Pb), As (S-As), and Cd (S-Cd) levels and urine Pb (U-Pb), As (U-As) and Cd (U-Cd) levels was observed in either group.Our study found low levels of serum and urine Hg in first-ever patients with AIS, providing new evidence of dysregulated heavy metals in patients with AIS.
Project description:Heavy metal pollution in the air, water, and soil has attracted substantial interest recently; however, assessment of the total human environmental exposure remains limited. Therefore, determining the total human environmental exposure is imperative for the management and control of heavy metal pollution. This study assessed the total environmental exposure levels of heavy metals as well as the exposure contributions of air, water, and soil, focusing on Hg, Cd, As, Pb, and Cr. Data from 3,855 volunteers from the cities of Taiyuan, Dalian, Shanghai, Wuhan, Chengdu, and Lanzhou allowed for comparison of the exposures in urban and rural areas. The levels of total human environmental exposure of Hg, Cd, As, Pb, and Cr were 1.82?×?10-6?mg/(kg·d), 1.58?×?10-6?mg/(kg·d), 3.87?×?10-5?mg/(kg·d), 1.79?×?10-5 and 7.47?×?10-5 mg/(kg·d), respectively. There were regional, urban-rural, sex, and age differences in the levels of heavy metal exposure. Water pollution was determined to be the largest contributor to heavy metal exposure, accounting for 97.87%, 92.50%, 80.51%, 76.16% and 79.46% of the Hg, Cd, As, Pb, and Cr, followed by air and soil pollution. These results can provide data to inform environmental protection policies and identify the priority pollutants that can help identify and prevent health risks due to overexposure to these heavy metal pollutants.
Project description:Acanthopanax senticosus extract with excessive standard of Pb, Cd, Hg, and Cu was used as the research object, and the alkyl thiourea functionalised silica was used as a new heavy metal removal scavenger. The heavy metal removal process was optimised by orthogonal experiment with dynamic and static adsorption modes. Meanwhile, the content of Acanthopanax B and Acanthopanax E, the solid content, and the HPLC fingerprint similarity were used as quality monitoring indicators of Acanthopanax senticosus heavy metal removal before and after. Then, the technical adaptability of heavy metal removal by alkyl thiourea functionalised silica was evaluated. Under the optimal dynamic adsorption conditions, the average removal rates of Pb, Cd, Hg, and Cu were 91.64%, 93.04%, 81.77%, and 83.11%, respectively. Under the optimal static adsorption conditions, the average removal rates of Pb, Cd, Hg, and Cu were 82.22%, 89.95%, 81.26%, and 82.97%, respectively. During Acanthopanax senticosus extract heavy metal removal before and after, the change percentage of Acanthopanax B and Acanthopanax E was less than 2.00%, the solid content loss rate was only 0.18%, and the fingerprint similarity was over 99.9%. The method can be used to satisfy the high efficiency of selective removal of harmful elements in Acanthopanax senticosus extract and the effective composition of almost no effect; the method is simple and easy, so it can be recommended for pretreatment of heavy metals in Traditional Chinese Medicine extracts, and this way provides a new thought and research technique to decrease the contents of heavy metals.