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1.
Biomed Pharmacother ; 141: 111923, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34328091

ABSTRACT

Although Zhusha Anshen Pill (ZSASP) is a commonly used traditional prescription for insomnia, the safety of cinnabar in the formula has always been controversial since its initial application in medical fields. Here, we developed a new prescription, Tieshuang Anshen Prescription (TSASP), by improving ZSASP with Fe2+ instead of Hg2+. Besides, TSASP was further optimized by establishing and testing the HPLC fingerprint and its sedative-hypnotic effect of formulas with different compatibility ratios and performing correlation spectrum analysis. The safety of TSASP was also evaluated by HE staining of liver and kidney. In addition, a validated and robust UHPLC-MS/MS method was established to demonstrate the pharmacokinetic characteristics of berberine, palmatine, jatrorrhizine, ligustilide, catalpol, loganin, liquiritin and liquiritigenin after oral administration of TSASP. Our study originally provides a new non-toxic prescription, TSASP, with better sedative-hypnotic effect in comparison with ZSASP, revealing that Fe2+ could replace Hg2+ to eliminate its toxicity and play a sedative role. Meanwhile, we believe that our pharmacokinetics results may contribute valuable reference to both TSASP's specific mechanism of action and its further clinical efficacy and effectiveness research.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Hypnotics and Sedatives/pharmacokinetics , Iron/pharmacokinetics , Locomotion/drug effects , Mercury/pharmacokinetics , Sleep/drug effects , Animals , Animals, Outbred Strains , Dose-Response Relationship, Drug , Drug Evaluation, Preclinical/methods , Drugs, Chinese Herbal/analysis , Drugs, Chinese Herbal/chemistry , Female , Hypnotics and Sedatives/analysis , Hypnotics and Sedatives/chemistry , Iron/analysis , Iron/chemistry , Locomotion/physiology , Male , Mercury/analysis , Mercury/chemistry , Mercury Compounds/analysis , Mercury Compounds/chemistry , Mercury Compounds/pharmacokinetics , Mice , Rats , Rats, Wistar , Sleep/physiology
2.
J Ethnopharmacol ; 250: 112489, 2020 Mar 25.
Article in English | MEDLINE | ID: mdl-31866510

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Baizi Yangxin Pills (BZYXP), a popular cinnabar (α-HgS) contained Traditional Chinese Medicines (TCMs) is widely used in clinical trials. However, mercury is one of the most toxic elements. The adverse effects of cinnabar-containing TCMs have been occasionally reported in recent years, leading to the growing concerns about their toxicity and safety. AIM OF THE STUDY: The health risks of BZYXP and cinnabar related to the mercury exposures were evaluated through blood pharmacokinetic and tissue distribution studies in rats. MATERIALS AND METHODS: The distribution of absorbed mercury in rats' blood and tissues were measured by the developed cold-vapor atomic fluorescence spectrometric method. And the tissue damages were determined through the histopathological examinations. For single dose study, the low and high oral doses were equivalent to 1 and 10-fold therapeutic dose, respectively. The multiple doses study was conducted at low and high dose levels every 12 h for 30 consecutive days. RESULTS: Significant differences of mercury blood pharmacokinetic and tissue distribution characteristics were observed between the corresponding BZYXP and cinnabar groups. The herbal ingredients in BZYXP promoted the absorption of bio-accessible mercury of cinnabar and prolonged the elimination process, posing potential health risks. Although mercury was found easily accumulated in kidney, liver and brain tissues, kidney and liver didn't show obvious damages even after 30 days consecutive administration of BZYXP or cinnabar at 10-fold clinically equivalent doses. But brain did show some histopathological changes, and autonomic activities of rats decreased, pointing the potential neurotoxicity. CONCLUSIONS: Mercury tend to be accumulated especially when over-dose or prolonged medication with cinnabar-containing TCMs are given. The mercury exposures even at therapeutic doses of BZYXP or cinnabar do pose health risks from the neurotoxicity point of view.


Subject(s)
Drugs, Chinese Herbal/administration & dosage , Medicine, Chinese Traditional/adverse effects , Mercury Compounds/administration & dosage , Neurotoxicity Syndromes/etiology , Animals , Brain/metabolism , Dose-Response Relationship, Drug , Drugs, Chinese Herbal/pharmacokinetics , Drugs, Chinese Herbal/toxicity , Female , Kidney/metabolism , Liver/metabolism , Male , Mercury Compounds/pharmacokinetics , Mercury Compounds/toxicity , Rats , Rats, Sprague-Dawley , Risk Assessment , Tissue Distribution
3.
Toxicol Appl Pharmacol ; 379: 114615, 2019 09 15.
Article in English | MEDLINE | ID: mdl-31175882

ABSTRACT

Mercury (Hg) is generally considered as a toxic metal; yet the biological outcomes of Hg-containing compounds are highly dependent upon their chemical forms. We hypothesize that mercury sulfide (HgS) is different from HgCl2 and methylmercury (MeHg) in producing intestinal Hg absorption and disruption of gut microbiome. To test this hypothesis, mice were given orally with HgS (α-HgS, 30 mg/kg), Zuotai (ß-HgS, 30 mg/kg), HgCl2 (33.6 mg/kg, equivalent Hg as HgS), or MeHg (3.1 mg/kg, 1/10 Hg as HgS) for 7 days. Accumulation of Hg in the duodenum and ileum after HgCl2 (30-40 fold) and MeHg (10-15 fold) was higher than HgS and Zuotai (~2-fold). HgCl2 and MeHg decreased intestinal intake peptide transporter-1 and Ost-ß, and increased ileal bile acid binding protein and equilibrative nucleoside transporter-1. The efflux transporters ATP-binding cassette sub-family C member-4 (Abcc4), Abcg2, Abcg5/8, and Abcb1b were increased by HgCl2 and to a lesser extent by MeHg, while HgS and Zuotai had minimal effects. Bacterial DNA was extracted and subjected to 16S rDNA sequencing. Operational taxonomic unit (OTU) results showed that among the 10 phyla, HgS increased Firmicutes, Proteobacteria, while HgCl2 increased Bacteroidetes, Cyanobacteria and decreased Firmicutes; among the 79 families, HgS increased Rikenellaceae, Lactobacillaceae, Helicobacteraceae, and decreased Prevotellaceae, while HgCl2 increased Odoribacteraceae, Porphyromonadaceae, and decreased Lactobacillaceae; among the 232 genus/species, HgS and Zuotai affected gut microbiome quite differently from HgCl2 and MeHg. qPCR analysis with 16S rRNA confirmed sequencing results. Thus, chemical forms of mercury are a major determinant for intestinal Hg accumulation, alterations in transporters and disruption of microbiome.


Subject(s)
Gastrointestinal Microbiome/drug effects , Intestinal Absorption/drug effects , Mercuric Chloride/toxicity , Mercury Compounds/pharmacokinetics , Animals , Duodenum/metabolism , Gastrointestinal Microbiome/genetics , Ileum/metabolism , Ileum/pathology , Male , Membrane Transport Proteins/drug effects , Membrane Transport Proteins/metabolism , Mercury Compounds/toxicity , Mice , RNA, Ribosomal, 16S/genetics , Real-Time Polymerase Chain Reaction
4.
Arch Environ Contam Toxicol ; 75(4): 634-646, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30238147

ABSTRACT

Silver nanoparticles, used mainly for their antibacterial properties, are among the most common manufactured nanomaterials. How they interact with aquatic organisms, especially how they cross biological membranes, remains uncertain. Free Ag+ ions, released from these nanoparticles, are known to play an important role in their overall bioavailability. In this project, we have studied the uptake of dissolved and nanoparticulate silver by liposomes. These unilamellar vesicles, composed of phospholipids, have long been used as models for natural biological membranes, notably to study the potential uptake of solutes by passive diffusion through the phospholipid bilayer. The liposomes were synthesized using extrusion techniques and were exposed over time to dissolved silver under different conditions where Ag+, AgS2O3-, or AgCl0 were the dominant species. Similar experiments were conducted with the complexes HgCl 2 0 and Cd(DDC) 2 0 , both of which are hydrophobic and known to diffuse passively through biological membranes. The uptake kinetics of Ag+, HgCl 2 0 , and Cd(DDC) 2 0 show no increase in internalized concentrations over time, unlike AgS2O3- and AgCl0, which appear to pass through the phospholipid bilayer. These results are in contradiction with our initial hypothesis that lipophilic Hg and Cd complexes would be able to cross the membrane, whereas silver would not. Encapsulated tritiated water inside the liposomes was shown to rapidly diffuse through the lipid bilayer, suggesting a high permeability. We hypothesize that monovalent anions or complexes as well as small neutral complexes with a strong dipole can diffuse through our model membrane. Finally, liposomes were exposed to 5-nm polyvinylpyrrolidone-coated silver nanoparticles over time. No significant uptake of nanoparticulate silver was observed. Neither disruption of the membrane nor invagination of nanoparticles into the liposomes was observed. This suggests that the main risk caused by AgNPs for nonendocytotic biological cells would be the elevation of the free silver concentration near the membrane surface due to adsorption of AgNPs and subsequent oxidation/dissolution.


Subject(s)
Lipid Bilayers/chemistry , Liposomes/chemistry , Metal Nanoparticles/chemistry , Silver/chemistry , Silver/pharmacokinetics , Adsorption , Aquatic Organisms , Biological Availability , Cations/chemistry , Diffusion , Lipid Bilayers/pharmacokinetics , Mercury Compounds/chemistry , Mercury Compounds/pharmacokinetics , Phospholipids/chemistry , Water Pollutants, Chemical/chemistry
5.
Neurotoxicol Teratol ; 66: 25-34, 2018.
Article in English | MEDLINE | ID: mdl-29366690

ABSTRACT

Zebrafish behavioral model is a powerful tool for neuroscience research. Behavioral changes in the zebrafish are studied by administering drugs. With the aid of automated and open-source MATLAB program, high-accuracy tracking of zebrafish can be achieved, and the important behavioral parameters can be calculated. Although mercury is accepted as a potent neurotoxin, used as a key element for preparing certain Ayurvedic medicines. In this work, mercury-based inorganic compounds, including HgCl2, HgS, and Ayurvedic medicines (Rasasindura and Kajjali) were administrated in zebrafish, and the effects on various behavioral parameters and cortisol levels were studied. A significant change in the basic locomotor parameters of fish was observed including speed (43% reduction), meander (150% increment), and a number of freeze points (125% increment), during 5-day treatment of HgCl2 along with a 3-fold increase in cortisol level against the control groups. Abnormal behavior was also recorded in color preference test, and novel tank diving behavior of HgCl2-treated groups, which can be attributed to the neurotoxicity induced by the HgCl2 administration. Contrary to this, the Rasasindura-treated group showed a significant increase in speed by 33%, decrease in meander by 20%, decrease in freeze points by 30%, and insignificant alteration in cortisol levels, which can be related to the rejuvenating nature of the Ayurvedic medicine Rasasindura. Additionally, Kajjali treated group did not show any substantial changes in zebrafish cortisol level and behavioral parameters except one in the diving test that indicates lowering stress. Similarly, HgS group showed normal behaviors except two irregular motor behaviors identical with the HgCl2 group. From these results, it can be concluded that the mercury-based Ayurvedic Rasasindura and Kajjali did not show any adverse effect or toxicity on zebrafish behavior model.


Subject(s)
Behavior, Animal/drug effects , Medicine, Ayurvedic , Mercury Compounds/toxicity , Mercury/toxicity , Motor Activity/drug effects , Neurotoxicity Syndromes/physiopathology , Zebrafish , Animals , Biological Availability , Disease Models, Animal , Dose-Response Relationship, Drug , Female , Hydrocortisone/analysis , Male , Mercury/pharmacokinetics , Mercury Compounds/pharmacokinetics , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/metabolism
6.
Biol Trace Elem Res ; 184(2): 536-545, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29130128

ABSTRACT

Zuotai, also named as "gTso thal", a known Tibetan medicinal mixture containing insoluble cubic crystal mercuric sulfide (ß-HgS), has been used to treat diseases with long history. The mercury release ratio from Zuotai in gastrointestinal environment is one determinant factor for its bioavailability and biological effect. However, the information is still scarce now. Therefore, the study was designed to investigate the effect of sulfhydryl biomolecules [L-cysteine (Cys) and glutathione (GSH)] and pH on mercury dissociation from Zuotai, ß-HgS, and hexagonal crystal mercuric sulfide (α-HgS) in artificial gastrointestinal juices or pure water with a 1:100 solid-liquid ratio. And, the digestion and peristalsis of gastrointestinal tract were simulated in vitro. The results showed the following trend for the mercury release ratio of Zuotai, artificial gastric juice > artificial intestinal juice > pure water, whereas the trend for ß-HgS and α-HgS was as follows, artificial intestinal fluid > artificial gastric fluid > pure water. The mercury release ratios of Zuotai, ß-HgS, and α-HgS significantly increased in artificial intestinal juice containing L-Cys or GSH compared to those without sulfhydryl biomolecules in the juice. However, in contrast to the results observed for ß-HgS and α-HgS, the mercury release ratio of Zuotai was reduced remarkably in pure water and artificial gastric juice with Cys or GSH. And, we found that strong acidic or strong alkaline environments promoted the dissociation of mercury from Zuotai, ß-HgS, and α-HgS. Taken together, current findings may contribute to other studies regarding clinical safety and bioavailability of the traditional drug Zuotai containing ß-HgS.


Subject(s)
Cysteine/pharmacology , Drug Liberation/drug effects , Glutathione/pharmacology , Mercury Compounds/pharmacokinetics , Mercury/pharmacokinetics , Biological Availability , Gastric Juice/chemistry , Gastric Juice/metabolism , Gastrointestinal Tract/metabolism , Hydrogen-Ion Concentration , Medicine, Tibetan Traditional , Mercury/chemistry , Mercury/metabolism , Mercury Compounds/chemistry , Mercury Compounds/metabolism , Water/chemistry , Water/metabolism
7.
Anal Chem ; 89(3): 2093-2100, 2017 02 07.
Article in English | MEDLINE | ID: mdl-28208276

ABSTRACT

Sensitive quantification of mercury distribution in fish is challenging because of insufficient sensitivities of conventional analytical methods, the limited mass of organs (tens of micrograms to several milligrams), and dilution of analyte concentration from sample digestion. In this work, a simple and robust approach coupling multiwall carbon nanotubes assisted matrix solid-phase dispersion (MWCNTs-MSPD) to single-drop solution electrode glow discharge-induced cold vapor generation (SD-SEGD-CVG) was developed for the sensitive determination of mercury in limited amount of sample. Mercury species contained in a limited amount of sample can be efficiently extracted into a 100 µL of eluent by MWCNTs-MSPD, which are conveniently converted to Hg0 by SD-SEGD-CVG and further transported to atomic fluorescence spectrometry for their determination. Therefore, analyte dilution resulted from sample preparation is avoided and sensitivity is significantly improved. On the basis of consumption of 1 mg of sample, a limit of detection of 0.01 µg L-1 (0.2 pg) was obtained with relative standard deviations (RSDs) of 5.2% and 4.6% for 2 and 20 µg L-1, respectively. The accuracy of the proposed method was validated by analysis of three Certified Reference Materials with satisfying results. To confirm that SD-SEGD-CVG-AFS coupling to MWCNTs-MSPD is a promising method to quantify mercury distribution in fish, this method was successfully applied for the sensitive determination of mercury in seven organs of common carps (muscle, gill, intestine, liver, gallbladder, brain, and eye) after dietary of mercury species. The proposed method provides advantages of minimum sample dilution, low blank, high sample introduction efficiency, high sensitivity, and minimum toxic chemicals and sample consumption.


Subject(s)
Carps/metabolism , Cold Temperature , Electrodes , Mercury Compounds/analysis , Animals , Dietary Exposure , Feasibility Studies , Limit of Detection , Mercury Compounds/classification , Mercury Compounds/pharmacokinetics , Microscopy, Electron, Scanning , Nanotubes, Carbon/chemistry , Reproducibility of Results , Spectrometry, Fluorescence/methods , Tissue Distribution
8.
Environ Pollut ; 213: 785-792, 2016 Jun.
Article in English | MEDLINE | ID: mdl-27038210

ABSTRACT

In the present study, the concentration of trace elements, total mercury (Hg) and selenium (Se) and mercury forms (MeHg, Hginorg and HgSe) in the vulnerable coastal dolphins Pontoporia blainvillei and Sotalia guianensis were appraised and compared, using metallothioneins (MT) and glutathione (GSH) as biomarkers for trace element exposure. The trace element concentrations varied between muscle and liver tissues, with liver of all dolphin specimens showing higher Hg and Se concentrations than those found in muscle. Hg, MeHg and Hginorg molar concentrations showed a clear increase with Se molar concentrations in the liver of both dolphins, and Se concentrations were higher than those of Hg on a molar basis. Se plays a relevant role in the detoxification of MeHg in the hepatic tissue of both dolphins, forming Hg-Se amorphous crystals in liver. In contrast, MT were involved in the detoxification process of Hginorg in liver. GSH levels in P. blainvillei and S. guianensis muscle tissue suggest that these dolphins have different diving capacities. Muscle Hg concentrations were associated to this tripeptide, which protects dolphin cells against Hg stress.


Subject(s)
Diving/physiology , Dolphins/metabolism , Glutathione/metabolism , Mercury/analysis , Metallothionein/metabolism , Selenium/analysis , Water Pollutants, Chemical/analysis , Animals , Biomarkers/metabolism , Brazil , Female , Inactivation, Metabolic , Liver/metabolism , Male , Mercury/pharmacokinetics , Mercury Compounds/analysis , Mercury Compounds/pharmacokinetics , Methylmercury Compounds/analysis , Methylmercury Compounds/pharmacokinetics , Muscles/metabolism , Oxidative Stress/drug effects , Selenium/pharmacokinetics , Selenium Compounds/analysis , Selenium Compounds/pharmacokinetics , Trace Elements/analysis , Trace Elements/pharmacokinetics , Water Pollutants, Chemical/pharmacokinetics
9.
Regul Toxicol Pharmacol ; 76: 51-6, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26804582

ABSTRACT

Traditional Chinese medicines (TCM) are increasingly being used as alternative medicines in many countries, and this has caused concern because of adverse health effects from toxic metal bioavailability such as mercury (Hg) and arsenic (As). The aim of this study was to investigate the bioavailability of As and Hg from TCM after a single exposure dose using an animal model of female Sprague-Dawley rats. The rats were divided into 6 groups which included four groups treated with sodium arsenite (NaAsO2), arsenic sulfide (As2S3), mercuric chloride (HgCl2), mercuric sulfide (HgS), and two groups treated with TCM containing high Hg or As (Liu Shen Wan: As 7.7-9.1% and Hg 1.4-5.0%; Niuhang Jie du Pian: As 6.2-7.9% and Hg <0.001%). The samples of urine, faeces, kidney and liver were collected for analysis and histological assay. The results indicated that relatively low levels of As and Hg from these TCM were retained in liver and kidney tissues. The levels of As in these tissues after TCM treatment were consistent with the levels from the As sulphide treated group. With the exception of the mercuric chloride treated group, the levels of Hg in urine from other groups were very low, and high levels of As and Hg from TCM were excreted in faeces. The study showed poor bioavailability of As and Hg from TCM as indicated by low relative bioavailability of As (0.60-1.10%) and Hg (<0.001%). Histopathological examination of rat kidney and liver tissues did not show toxic effects from TCM.


Subject(s)
Arsenicals/pharmacokinetics , Arsenites/pharmacokinetics , Drug Contamination , Drugs, Chinese Herbal/pharmacokinetics , Mercuric Chloride/pharmacokinetics , Mercury Compounds/pharmacokinetics , Sodium Compounds/pharmacokinetics , Sulfides/pharmacokinetics , Administration, Oral , Animals , Arsenicals/administration & dosage , Arsenicals/urine , Arsenites/administration & dosage , Arsenites/toxicity , Arsenites/urine , Biological Availability , Drugs, Chinese Herbal/administration & dosage , Drugs, Chinese Herbal/toxicity , Feces/chemistry , Female , Kidney/drug effects , Kidney/metabolism , Liver/drug effects , Liver/metabolism , Mercuric Chloride/administration & dosage , Mercuric Chloride/toxicity , Mercuric Chloride/urine , Mercury Compounds/administration & dosage , Mercury Compounds/toxicity , Mercury Compounds/urine , Rats, Sprague-Dawley , Risk Assessment , Sodium Compounds/administration & dosage , Sodium Compounds/toxicity , Sodium Compounds/urine , Sulfides/administration & dosage , Sulfides/toxicity , Sulfides/urine , Tissue Distribution
10.
Zhongguo Zhong Yao Za Zhi ; 40(12): 2455-60, 2015 Jun.
Article in Chinese | MEDLINE | ID: mdl-26591542

ABSTRACT

α-HgS is the main component of traditional Chinese medicine cinnabar, while ß-HgS is the main component of Tibetan medicine Zuotai. However, there was no comparative study on the dissolution and absorption in gastrointestinal tract and bioaccumulation in organs of mercury in Cinnabar, Zuotai, α-HgS and ß-HgS. In this study, the dissolution process of the four compounds in the human gastrointestinal tract was simulated to determine the mercury dissolutions and compare the mercury dissolution of different medicines and the dissolution-promoting capacity of different solutions. To explore the absorption and bioaccumulation of cinnabar and Zuotai in organisms, mice were orally administered with clinical equivalent doses cinnabar and Zuotai. Meanwhile, a group of mice was given α-HgS and ß-HgS with the equivalent mercury with cinnabar, while another group was given ß-HgS and HgCl2 with the equivalent mercury with Zuotai. The mercury absorption and bioaccumulation capacities of different medicines in mice and their mercury bioaccumulation in different tissues and organs were compared. The experimental results showed a high mercury dissolutions of Zuotai in artificial gastrointestinal fluid, which was followed by ß-HgS, cinnabar and α-HgS. As for the mercury absorption and bioaccumulation in mice, HgCl2 was the highest, ß-HgS was the next, and a-HgS was slightly higher than cinnabar. The organs with the mercury bioaccumulation from high to low were kidney, liver and brain. This study is close to clinical practices and can provide reference for the clinical safe medication as well as a study model for the safety evaluation on heavy metal-containing medicines by observing the mercury dissolution, absorption, distribution and accumulation of mercury-containing medicines cinnabar and zuotai.


Subject(s)
Drugs, Chinese Herbal/pharmacokinetics , Gastrointestinal Tract/metabolism , Mercury Compounds/pharmacokinetics , Animals , Brain/metabolism , Drugs, Chinese Herbal/chemistry , Kidney/metabolism , Liver/metabolism , Male , Mercury/chemistry , Mercury/pharmacokinetics , Mercury Compounds/chemistry , Mice , Solubility
11.
Environ Res ; 143(Pt A): 55-61, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26436307

ABSTRACT

Mercury accumulates at high levels in marine mammal tissues. However, its speciation is poorly understood. The main goal of this investigation was to establish the relationships among mercury species and selenium (Se) concentrations in toothed-whale muscles at different mercury levels. The concentrations of total mercury (T-Hg), methylmercury (MeHg), inorganic mercury (I-Hg) and Se were determined in the muscles of four toothed-whale species: bottlenose dolphins (n=31), Risso's dolphins (n=30), striped dolphins (n=29), and short-finned pilot whales (n=30). In each species, the MeHg concentration increased with increasing T-Hg concentration, tending to reach a plateau. In contrast, the proportion of MeHg in T-Hg decreased from 90-100% to 20-40%. The levels of T-Hg and Se showed strong positive correlations. Se/I-Hg molar ratios rapidly decreased with the increase of I-Hg and reached almost 1 in all species. These results suggested that the demethylated MeHg immediately formed Se/I-Hg equimolar complex of mercury selenide (HgSe) in their muscles. In addition, an X-ray absorption fine structure analysis (XAFS) of a bottlenose dolphin muscle confirmed that the dominant chemical form of the Se/I-Hg equimolar complex was HgSe. HgSe was mainly localized in cells near the endomysium using electron probe microanalysis (EPMA). These results suggested that the demethylated MeHg finally deposits within muscle cells of bottlenose dolphin as an inert HgSe.


Subject(s)
Dolphins/metabolism , Mercury/pharmacokinetics , Muscles/metabolism , Selenium/pharmacokinetics , Animals , Electron Probe Microanalysis , Environmental Monitoring , Female , Male , Mercury Compounds/pharmacokinetics , Methylmercury Compounds/pharmacokinetics , Selenium Compounds/pharmacokinetics , Species Specificity , Water Pollutants, Chemical/pharmacokinetics , X-Ray Absorption Spectroscopy
12.
Biomed Res Int ; 2015: 280958, 2015.
Article in English | MEDLINE | ID: mdl-25734058

ABSTRACT

The purpose of this study was to investigate whether cinnabar causes renal inflammation and fibrosis in rats. Rats were dosed orally with cinnabar (1 g/kg/day) for 8 weeks or 12 weeks. The control rats were treated with solvent (5% carboxymethylcellulose solution) over the same time periods, respectively. Renal mercury (RHg), urinary mercury (UHg), serum creatinine (SCr), urine kidney injury molecule 1 (KIM-1), renal pathology, and renal mediators were examined. At both 8 weeks and 12 weeks, RHg, UHg, and urine KIM-1 were significantly higher in the cinnabar group than in the control group, although SCr was unchanged. Kidney lesions in the cinnabar-treated rats occurred mainly in the tubules and interstitium, including vacuolization, protein casts, infiltration of inflammatory cells, and slight increase in interstitial collagen. In addition, mild mesangial proliferation was observed in glomeruli. Moreover, the expression of inflammatory and fibrogenic mediators was upregulated in the cinnabar group. In conclusion, cinnabar may cause kidney damage due to the accumulation of mercury, and renal inflammation and slight fibrogenesis may occur in rats. In the clinic, the potential risk of renal injury due to the prolonged consumption of cinnabar should be considered even though the agent is relatively nontoxic.


Subject(s)
Kidney/metabolism , Kidney/pathology , Mercury Compounds/adverse effects , Mercury Compounds/pharmacokinetics , Nephritis/chemically induced , Nephritis/metabolism , Administration, Oral , Animals , Fibrosis/chemically induced , Fibrosis/metabolism , Fibrosis/pathology , Kidney/drug effects , Mercury Compounds/administration & dosage , Metabolic Clearance Rate , Nephritis/pathology , Rats , Rats, Sprague-Dawley
13.
J Dent Res ; 94(4): 615-21, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25691072

ABSTRACT

The ability to infiltrate various molecules and resins into dental enamel is highly desirable in dentistry, yet transporting materials into dental enamel is limited by the nanometric scale of their pores. Materials that cannot be infiltrated into enamel by diffusion/capillarity are often considered molecules with sizes above a critical threshold, which are often considered to be larger than the pores of enamel. We challenge this notion by reporting the use of electrokinetic flow to transport solutions with molecules with sizes above a critical threshold-namely, an aqueous solution with a high refractive index (Thoulet's solution) and a curable fluid resin infiltrant (without acid etching)-deep into the normal enamel layer. Volume infiltration by Thoulet's solution is increased by 5- to 6-fold, and resin infiltration depths as large as 600 to 2,000 µm were achieved, in contrast to ~10 µm resulting from diffusion/capillarity. Incubation with demineralization solution for 192 h resulted in significant demineralization at noninfiltrated histologic points but not at resin infiltrated. These results open new avenues for the transport of materials in dental enamel.


Subject(s)
Dental Enamel/metabolism , Electroosmosis/methods , Electrophoresis/methods , Nanopores/ultrastructure , Adolescent , Adult , Algorithms , Capillary Action , Dental Enamel/ultrastructure , Dental Pulp Cavity/metabolism , Dental Pulp Cavity/ultrastructure , Dentin/metabolism , Dentin/ultrastructure , Diffusion , Humans , Iodides/pharmacokinetics , Mercury Compounds/pharmacokinetics , Microfluidics/instrumentation , Microfluidics/methods , Potassium Chloride/pharmacokinetics , Potassium Iodide/pharmacokinetics , Resins, Synthetic/chemistry , Young Adult
15.
Sci Total Environ ; 454-455: 9-15, 2013 Jun 01.
Article in English | MEDLINE | ID: mdl-23538135

ABSTRACT

Five Ayurvedic medicines with mercury concentrations of 85mg/kg and higher were characterized with respect to their speciation and their bioaccessibility. X-ray absorption spectroscopy revealed that the mercury in the Ayurvedic medicines was inorganic and best matched to cinnabar, even in samples that had been hypothesized to contain mercury through plant sources only. The bioaccessibility (bioaccessible concentrations and percent bioaccessibility) was measured using two methods: a two-phase physiologically based extraction test (PBET gastric, G and gastric+intestinal phase, GI); and the fed organic estimation human simulation test (FOREhST). The percent bioaccessibility of mercury in all Ayurvedic samples was very low (<5%), corresponding to the low solubility of cinnabar, but it increased with increasing dissolved organic carbon content of the bioaccessibility solutions (PBET-G

Subject(s)
Environmental Monitoring/methods , Gastrointestinal Tract/metabolism , Materia Medica/pharmacokinetics , Medicine, Ayurvedic , Mercury Compounds/pharmacokinetics , Biological Availability , Humans , India , Materia Medica/analysis , Mercury Compounds/analysis , Plant Extracts/analysis , Plant Extracts/pharmacokinetics , Risk Assessment/methods , Spectrometry, X-Ray Emission , X-Ray Absorption Spectroscopy
16.
Basic Clin Pharmacol Toxicol ; 112(6): 412-7, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23302034

ABSTRACT

The toxicity of cinnabar, a naturally occurring mercury sulphide (HgS), has long been referred to soluble mercury chloride (HgCl2 ). To investigate whether the speciation of mercury plays a role in its disposition and toxicity, we hereby investigated and compared cinnabar with soluble HgCl2 and pure insoluble HgS in mice on mercury absorption, tissue distribution and in relation to the biological effects. The male C57BL/6J mice were treated by oral administration of various doses of cinnabar, with 0.01 g/kg of HgCl2 for comparison, or the same dose of cinnabar or pure HgS (0.1 g/kg), once a day for 10 consecutive days. The total mercury contents in serum and tissue (brain, kidney, liver) were measured by atomic fluorescence spectrometer (AFS). The biological effects investigated involved monoamine neurotransmitters (serotonin, 5-HT) in brain as an indicator of therapeutic function, and serum alanine transaminase (ALT) as a marker of hepatic damage, blood urea nitrogen (BUN) and serum creatinine as markers for renal function. The mercury absorption of cinnabar or HgS was much less than that of HgCl2 . The mercury levels in brains of the cinnabar group were only slightly changed and kept in a steady-state with the dose elevated. Cinnabar or HgS suppressed brain 5-HT levels. HgCl2 could not cause any changes in brain 5-HT although the mercury level increased considerably. The results revealed that cinnabar or HgS is markedly different from HgCl2 in mercury absorption, tissue distribution and influence on brain 5-HT levels, which suggests that the pharmacological and/or toxicological effects of cinnabar undertake other pathways from mercuric ions.


Subject(s)
Brain/drug effects , Mercuric Chloride/pharmacokinetics , Mercury Compounds/pharmacokinetics , Serotonin/metabolism , Adsorption , Animals , Biomarkers/metabolism , Brain/metabolism , Dose-Response Relationship, Drug , Kidney/drug effects , Kidney/metabolism , Kidney Function Tests , Liver/drug effects , Liver/metabolism , Liver Function Tests , Male , Mercuric Chloride/administration & dosage , Mercuric Chloride/blood , Mercuric Chloride/toxicity , Mercury Compounds/administration & dosage , Mercury Compounds/blood , Mercury Compounds/toxicity , Mice , Mice, Inbred C57BL , Tissue Distribution
17.
Arch Environ Contam Toxicol ; 63(4): 495-502, 2012 Nov.
Article in English | MEDLINE | ID: mdl-22961217

ABSTRACT

Along the Israeli Mediterranean Coast, three areas are considered "hot spots" of mercury (Hg) pollution: (1) Northern Haifa Bay (NHB), (2) the lower Qishon River at the southern part of Haifa Bay, and (3) a marine outfall of activated sewage sludge at the southern coast off Palmachim (sewage-sludge disposal site [SDS]). Even though the total Hg (HgT) concentrations in the sediments at the three areas are of the same order of magnitude (250-500 µg kg(-1)), Hg was shown to bioaccumulate in fish and benthic fauna from Haifa Bay but not in benthic fauna or in commercial fish caught along the southern Mediterranean Coast of Israel near the SDS outfall. The primary goal of this study was to measure the concentrations of Hg species (HgT, methyl-Hg [MeHg], and Hg in different biogeochemical fractions)-in conjunction with organic carbon-in sediments of NHB and the lower Qishon River to assess its impact on Hg transitions among the species as characterized by different bioavailability and bioaccessibility. HgT concentrations in NHB and the Qishon River ranged from 249 to 347 and 165 to 667 µg kg(-1), respectively. MeHg was significantly higher in the Qishon River (6.3-34.0 µg kg(-1)) than in NHB (0.22-0.70 µg kg(-1)) as were total organic carbon (TOC) concentrations (average 2.5 vs. 0.13 %). The relative Hg distribution in the biogeochemical fractions in NHB was 2.3 % in the most bioaccessible fractions (F1 + F2), 55 % in the organo-chelated species fraction (F3), 42 % in the strong-complexed species fraction (F4), and 0.7 % in the mercuric-sulfide fraction (F5). In the Qishon River, the bioavailable F1 + F2 and F3 fractions were lower than in NHB (<0.01 and 23 %, respectively) and the more refractory F4 and F5 fractions higher (73 and 3.3 %, respectively). The fractionation of Hg in Qishon River sediments was similar to the distribution found in polluted stations at the SDS. TOC and MeHg were positively and negatively correlated, respectively, in Qishon River and NHB sediments. Methylation depended on TOC availability when its concentration was in the range of 2-4 wt%. It is possible that TOC in the sediment controlled Hg speciation: Hg in F3 decreased and in F4 increased with increasing TOC concentrations. In contrast, MeHg/HgT was significantly positively correlated with TOC and Hg in the stable F4 fraction and negatively correlated with Hg in the F3 fraction. It was therefore assumed that higher TOC concentrations enhanced microbial activity and decomposition of organic matter. Hg was released from the F3 fraction and was either transferred to the F4 fraction or made available for methylation processes.


Subject(s)
Carbon/analysis , Environmental Monitoring/methods , Geologic Sediments/chemistry , Mercury/analysis , Water Pollutants, Chemical/analysis , Animals , Bays/chemistry , Biological Availability , Carbon/pharmacokinetics , Fishes/metabolism , Israel , Mediterranean Sea , Mercury/pharmacokinetics , Mercury Compounds/analysis , Mercury Compounds/pharmacokinetics , Rivers/chemistry , Sewage/chemistry
18.
Zhongguo Zhong Yao Za Zhi ; 37(6): 750-3, 2012 Mar.
Article in Chinese | MEDLINE | ID: mdl-22715715

ABSTRACT

Mercury-containing preparations are widely used in surgery department of traditional Chinese medicine and have made remarkable achievements. But they are toxic to human kidney, nerve, immune, etc. Smilacis Glabrae Rhizoma is sweet, tasteless and neutral in nature and able to enter liver and stomach channels and detoxify mercury poisoning. This article summarizes the mercury poisoning and the detoxification effect of Smilacis Glabrae Rhizoma in ancient records, pharmaceutical studies and clinical application, in order to provide ideas and methods for the safe use of mercury-containing preparations in surgery department of traditional Chinese medicine.


Subject(s)
Drugs, Chinese Herbal/therapeutic use , Liliaceae/chemistry , Mercury Compounds/pharmacokinetics , Mercury Poisoning/prevention & control , Plants, Medicinal/chemistry , Gastric Mucosa/metabolism , Humans , Inactivation, Metabolic , Liver/drug effects , Liver/metabolism , Medicine, Chinese Traditional , Mercury Compounds/adverse effects , Mercury Compounds/therapeutic use , Rhizome/chemistry , Stomach/drug effects
19.
Ecotoxicology ; 21(3): 882-7, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22249488

ABSTRACT

Nonlethal indices of contaminant exposure can facilitate research on the accumulation and effects of contaminants in wildlife. Here, we tested the efficacy of using amputated toes ("toe clips"), a common byproduct when marking amphibians in population and genetic studies, to determine mercury (Hg) concentrations in amphibians. We examined total mercury (THg) concentrations in American toads (Bufo americanus) collected along a contamination gradient at a Hg-contaminated field site. We found significant positive correlations between toe THg and blood THg concentrations in adult males and females collected in two different years. We also found that blood and toe clips could be used to predict maternal transfer of Hg, an important mechanism of reproductive toxicity in wildlife. Maternal toe THg concentrations were more highly correlated with egg THg concentrations than were maternal blood THg concentrations. Our results indicate that amputated toes are effective for identifying Hg concentrations in amphibians.


Subject(s)
Bufonidae/metabolism , Mercury Compounds/pharmacokinetics , Mercury Poisoning/blood , Ovum/metabolism , Water Pollutants, Chemical/pharmacokinetics , Amputation, Surgical , Animal Identification Systems , Animals , Environmental Monitoring , Female , Male , Maternal Exposure , Mercury Compounds/analysis , Ovum/chemistry , Toes/surgery , Water Pollutants, Chemical/analysis
20.
Ecotoxicology ; 21(3): 705-18, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22193540

ABSTRACT

Lake Champlain continues to experience mercury contamination resulting in public advisories to limit human consumption of top trophic level fish such as walleye. Prior research suggested that mercury levels in biota could be modified by differences in ecosystem productivity as well as mercury loadings. We investigated relationships between mercury in different trophic levels in Lake Champlain. We measured inorganic and methyl mercury in water, seston, and two size fractions of zooplankton from 13 sites representing a range of nutrient loading conditions and productivity. Biomass varied significantly across lake segments in all measured ecosystem compartments in response to significant differences in nutrient levels. Local environmental factors such as alkalinity influenced the partitioning of mercury between water and seston. Mercury incorporation into biota was influenced by the biomass and mercury content of different ecosystem strata. Pelagic fish tissue mercury was a function of fish length and the size of the mercury pool associated with large zooplankton. We used these observations to parameterize a model of mercury transfers in the Lake Champlain food web that accounts for ecosystem productivity effects. Simulations using the mercury trophic transfer model suggest that reductions of 25-75% in summertime dissolved eplimnetic total mercury will likely allow fish tissue mercury concentrations to drop to the target level of 0.3 µg g(-1) in a 40-cm fish in all lake segments. Changes in nutrient loading and ecosystem productivity in eutrophic segments may delay any response to reduced dissolved mercury and may result in increases in fish tissue mercury.


Subject(s)
Environmental Monitoring/methods , Food Chain , Lakes , Mercury Compounds/analysis , Water Pollutants, Chemical/analysis , Zooplankton/drug effects , Animals , Biomass , Fishes/metabolism , Food Contamination/analysis , Hydrogen-Ion Concentration , Mercury Compounds/pharmacokinetics , Models, Biological , Water Pollutants, Chemical/pharmacokinetics , Zooplankton/physiology
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