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Compatibility of Niuhuang Jiedu Tablets Results in Attenuated Arsenic Bioaccumulation and Consequent Protection against Realgar-Induced Toxicity in Mice

ABSTRACT: Niuhuang Jiedu Tablets (NJT) is a popular over-the-counter traditional Chinese medicine (TCM) preparation. It is composed of realgar (As2S2) and seven other TCMs. The safety of NJT is of growing concern because arsenic (As) is carcinogenic to humans. The toxicity of realgar in vivo can mainly be attributed to the absorbed and accumulated As. This study investigated the correlation between the detoxification effects of the other TCMs in NJT on realgar and their influences on arsenic accumulation of realgar in mice. Histopathological examination, clinical biochemical test, and metabolic profiling analysis were used to evaluate the toxicity of realgar. The concentration of arsenic in mice whole blood as the hazard indicator was determined by inductively coupled plasma mass spectrometry (ICP-MS). The compatibility of NJT could decrease arsenic bioaccumulation of realgar in mice whole blood and consequently reduce the toxicity of realgar, which could be considered as one detoxification mechanism to realgar in NJT. The combination of Rhei Radix et Rhizoma, Scutellariae Radix, Platycodonis Radix, and Glycyrrhizae Radix et Rhizoma exhibited almost the same effects as NJT in regulating the serum biochemical parameters and metabolic profiles disturbed by realgar and in reducing arsenic accumulation of realgar in mice whole blood.

SUBMITTER: Xu W

PROVIDER: S-EPMC9273386 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Realgar, an arsenic-containing traditional Chinese medicine of As2S2, has significant therapeutic effects for hundreds of years. NiuHuangJieDu tablets (NHJDT) is one of the most commonly prescribed realgar-containing preparations for the treatment of sore throat, swelling, and aching of gums. However, realgar-containing TCMs raise great safety concerns due to the adverse effects reported by arsenic poisoning. In this study, the arsenic-related health risk assessment of NHJDT was conducted in healthy volunteers after single and multiple doses oral administration. Blood, plasma, and urine samples were collected after dosing at predetermined time points or periods. Simple, rapid, and sensitive methods were established for the quantification of total arsenic and arsenic speciation in biological samples. The total arsenic and arsenic speciation were determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) and high-performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS), respectively. No significant fluctuation of total arsenic was observed in human blood, and no traces of arsenic speciation were found in human plasma. Dimethylarsenic acid was detected as the predominated arsenic species in human urine after dosing. Therapeutic dose administration of NHJDT was relatively safe in single dose for the limited blood arsenic exposure, but long-term medication may still pose health risks due to the accumulation of arsenics in blood and its extremely slow excretion rate. Therefore, arsenic exposure should be carefully monitored during realgar-containing TCM medication, especially for long-term regimen. The results obtained in this study will provide scientific references for the clinical application of realgar and its-containing TCMs.

| S-EPMC8776706 | biostudies-literature

Extreme Arsenic Bioaccumulation Factor Variability in Lake Titicaca, Bolivia.

Project description:Latin America, like other areas in the world, is faced with the problem of high arsenic (As) background in surface and groundwater, with impacts on human health. We studied As biogeochemical cycling by periphyton in Lake Titicaca and the mine-impacted Lake Uru Uru. As concentration was measured in water, sediment, totora plants (Schoenoplectus californicus) and periphyton growing on stems, and As speciation was determined by X-ray absorption spectroscopy in bulk and EDTA-extracted periphyton. Dissolved arsenic was between 5.0 and 15 ?g L-1 in Lake Titicaca and reached 78.5 ?g L-1 in Lake Uru Uru. As accumulation in periphyton was highly variable. We report the highest As bioaccumulation factors ever measured (BAFsperiphyton up to 245,000) in one zone of Lake Titicaca, with As present as As(V) and monomethyl-As (MMA(V)). Non-accumulating periphyton found in the other sites presented BAFsperiphyton between 1281 and 11,962, with As present as As(III), As(V) and arsenosugars. DNA analysis evidenced several taxa possibly related to this phenomenon. Further screening of bacterial and algal isolates would be necessary to identify the organism(s) responsible for As hyperaccumulation. Impacts on the ecosystem and human health appear limited, but such organisms or consortia would be of great interest for the treatment of As contaminated water.

| S-EPMC6650431 | biostudies-literature

Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma.

Project description:Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow, remains incurable despite the use of novel and conventional therapies. In this study, we demonstrated MM cell cytotoxicity triggered by realgar (REA; As4 S4 ) nanoparticles (NREA) versus Arsenic trioxide (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo anti-MM activity, resulting in significantly decreased tumour burden. The anti-MM activity of NREA and ATO is associated with apoptosis, evidenced by DNA fragmentation, depletion of mitochondrial membrane potential, cleavage of caspases and anti-apoptotic proteins. NREA induced G2 /M cell cycle arrest and modulation of cyclin B1, p53 (TP53), p21 (CDKN1A), Puma (BBC3) and Wee-1 (WEE1). Moreover, NREA induced modulation of key regulatory molecules in MM pathogenesis including JNK activation, c-Myc (MYC), BRD4, and histones. Importantly, NREA, but not ATO, significantly depleted the proportion and clonogenicity of the MM stem-like side population, even in the context of the bone marrow stromal cells. Finally, our study showed that both NREA and ATO triggered synergistic anti-MM activity when combined with lenalidomide or melphalan. Taken together, the anti-MM activity of NREA was more potent compared to ATO, providing the preclinical framework for clinical trials to improve patient outcome in MM.

| S-EPMC5705577 | biostudies-literature

Bioaccumulation

Project description:Bioaccumulation experiment

| PRJEB20879 | ENA

Arsenic bioaccumulation in subarctic fishes of a mine-impacted bay on Great Slave Lake, Northwest Territories, Canada.

Project description:A subarctic fish community in mine-impacted Yellowknife Bay (Great Slave Lake, Northwest Territories, Canada) was investigated for biological and ecological processes controlling arsenic bioaccumulation. Total concentrations of arsenic, antimony, and metals were measured in over 400 fishes representing 13 species, and primary producers and consumers were included to characterize food web transfer. Yellowknife Bay had slightly more arsenic in surface waters (~3 ?g/L) relative to the main body of Great Slave Lake (<1 ?g/L), resulting in two-fold higher total arsenic concentrations in muscle of burbot (Lota lota), lake whitefish (Coregonus clupeaformis), and northern pike (Esox lucius). Other mining-associated contaminants, specifically antimony, lead, and silver, were typically below analytical detection in those fish species. No evidence was found for enhanced bioaccumulation of arsenic in long-lived, slow-growing subarctic fishes. Food web biodilution of total arsenic occurred between primary producers, aquatic invertebrates, and fish, although trophic position did not explain arsenic concentrations among fishes. Pelagic-feeding species had higher total arsenic concentrations compared to littoral fishes. Arsenic accumulated in subarctic fishes to comparable levels as fishes from lakes around the world with similar water arsenic concentrations. This first comprehensive study for a subarctic freshwater food web identified the importance of water exposure, biodilution, and habitat-specific feeding on arsenic bioaccumulation.

| S-EPMC6707560 | biostudies-literature

Arsenic and Mercury Containing Traditional Chinese Medicine (Realgar and Cinnabar) Strongly Inhibit Organic Anion Transporters, Oat1 and Oat3, In Vivo in Mice.

Project description:Toxic heavy metals, including mercury (Hg) and arsenic (As), accumulate preferentially in kidneys and always cause acute renal failure. The aim of this study was to investigate whether these samples affect organic anion transporters, Oat1 and Oat3, in vivo in mice kidney. Mice (n = 10) were orally treated with investigational samples. After last administration, all mice were i.v. p-aminohippuric acid (PAH), and the blood and kidneys samples were collected. The concentrations of PAH were quantified by spectrophotometry. mRNA expressions of Oat1 and Oat3 were assayed by real-time PCR. In comparison with corresponding control, major pharmacokinetic parameters of PAH in sera were significantly changed by investigational samples (p < 0.05), PAH accumulations in the kidney tissues were significantly higher (p < 0.05), PAH uptake by renal slices was greatly reduced, Oat1 and Oat3 mRNA expression were significantly inhibited in investigational sample groups. Arsenic and mercury containing traditional Chinese medicine (Realgar and Cinnabar) probably induce kidney damage through inhibiting several members of the organic anion transporters (such as OAT1 and OAT3).

| S-EPMC4695662 | biostudies-literature

Ecosystem Protection through Myco-Remediation of Chromium and Arsenic.

Project description:The current study emphasizes fungi as an important tool against heavy metals and how isolated fungal species can be used to create a successful strategy for the bioremediation of chromium and arsenic-contaminated sites/soils. Globally, heavy metal pollution is a serious issue. In the current investigation, contaminated sites were chosen, and samples could be taken from various localities of Hisar (29.1492° N, 75.7217° E) and Panipat (29.3909° N, 76.9635° E), India. A total of 19 fungal isolates were obtained from the collected samples through the enrichment culture technique using PDA media supplemented with Cr as chromic chloride hexahydrate (50 mg/L) and As as sodium arsenate (10 mg/L) and the potential of fungal isolates to be used for the removal of heavy metals was examined. The isolates were screened for minimum inhibitory concentrations (MIC) exhibiting tolerance capabilities, and the four best isolates C1, C3, A2, and A6 with the highest MICs (>5000 mg/L), were chosen for further investigations. To use the chosen isolates in the remediation of heavy metals (Cr and As), the culture conditions were optimized. The fungal isolates C1 and C3 estimated the highest removal of 58.60% and 57.00% at 50 mg/L chromium concentration, while the isolates A6 and A2 recorded the highest removal efficiency of 80% and 56% at 10 mg/L arsenic concentration under optimal conditions. Finally, the chosen fungal isolates C1 and A6 were molecularly identified as Aspergillus tamarii and Aspergillus ustus, respectively.

| S-EPMC10055941 | biostudies-literature

Data on the sub-chronic toxicity in rats after 30 days of oral realgar administration and the accumulation and distribution of arsenic species.

Project description:These data are related to the research "The accumulation and distribution of arsenic species and association with arsenic toxicity in rats after 30 days of oral realgar administration" (Yi et al., 2019) [1]. These data include the rat body weights, haematology, electrolytes, coagulation and biochemical parameters, and relative organ weights after 30 days of oral administration of realgar, which was consistent with the current OECD guideline "Repeated Dose 28-Day oral Toxicity Study in Rodents". The data also include the content of arsenite (As(III)), arsenate (As(V)), dimethylarsinic acid (DMA), monomethylarsonic acid (MMAV), arsenic betaine (AsB) and arsenic chrome (AsC) in rat blood, liver, kidneys, brain and urine after single-dose and 30-day oral administration of realgar. The provided data are intended to demonstrate whether realgar has short-term toxicity and the role of accumulated arsenic species in realgar toxicity.

| S-EPMC6657230 | biostudies-literature

Bioaccumulation and detoxification of trivalent arsenic by Achromobacter xylosoxidans BHW-15 and electrochemical detection of its transformation efficiency.

Project description:Arsenotrophic bacteria play an essential role in lowering arsenic contamination by converting toxic arsenite [As (III)] to less toxic and less bio-accumulative arsenate [As (V)]. The current study focused on the qualitative and electrocatalytic detection of the arsenite oxidation potential of an arsenite-oxidizing bacteria A. xylosoxidans BHW-15 (retrieved from As-contaminated tube well water), which could significantly contribute to arsenic detoxification, accumulation, and immobilization while also providing a scientific foundation for future electrochemical sensor development. The minimum inhibitory concentration (MIC) value for the bacteria was 15 mM As (III). Scanning Electron Microscopy (SEM) investigation validated its intracellular As uptake capacity and demonstrated a substantial association with the MIC value. During the stationary phase, the strain's As (III) transformation efficiency was 0.0224 mM/h. Molecular analysis by real-time qPCR showed arsenite oxidase (aioA) gene expression increased 1.6-fold in the presence of As (III) compared to the untreated cells. The immobilized whole-cell also showed As (III) conversion up to 18 days. To analyze the electrochemical oxidation in water, we developed a modified GCE/P-Arg/ErGO-AuNPs electrode, which successfully sensed and quantified conversion of As (III) into As (V) by accepting electrons; implying a functional As oxidase enzyme activity in the cells. To the best of our knowledge, this is the first report on the electrochemical observation of the As-transformation mechanism with Achromobacter sp. Furthermore, the current work highlighted that our isolate might be employed as a promising candidate for arsenic bioremediation, and information acquired from this study may be helpful to open a new window for the development of a cost-effective, eco-friendly biosensor for arsenic species detection in the future.

| S-EPMC8556249 | biostudies-literature

Enhanced Bioaccumulation and Toxicity of Arsenic in Marine Mussel Perna viridis in the Presence of CuO/Fe3O4 Nanoparticles.

Project description:Leakage of metal oxide nanoparticles (MNPs) into marine environments is inevitable with the increasing use of MNPs. However, little is known about the effects of these lately emerged MNPs on the bioaccumulation and toxicity of pre-existing contaminants in marine biota. The current study therefore investigated the effects of two common MNPs, CuO nanoparticles (nCuO) and Fe3O4 nanoparticles (nFe3O4), on bioaccumulation and toxicity of arsenic (As) in green mussel Perna viridis. Newly introduced MNPs remarkably promoted the accumulation of As and disrupted the As distribution in mussels because of the strong adsorption of As onto MNPs. Moreover, MNPs enhanced the toxicity of As by disturbing osmoregulation in mussels, which could be supported by decreased activity of Na+-K+-ATPase and average weight loss of mussels after MNPs exposure. In addition, the enhanced toxicity of As in mussels might be due to that MNPs reduced the biotransformation efficiency of more toxic inorganic As to less toxic organic As, showing an inhibitory effect on As detoxifying process of mussels. This could be further demonstrated by the overproduction of reactive oxygen species (ROS), as implied by the rise in quantities of superoxide dismutase (SOD) and lipid peroxidation (LPO), and subsequently restraining the glutathione-S-transferases (GST) activity and glutathione (GSH) content in mussels. Taken together, this study elucidated that MNPs may elevate As bioaccumulation and limit As biotransformation in mussels, which would result in an enhanced ecotoxicity of As towards marine organisms.

| S-EPMC8538411 | biostudies-literature

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