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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

Endophytic Fungi Piriformospora indica Mediated Protection of Host from Arsenic Toxicity.

Project description:Complex intercellular interaction is a common theme in plant-pathogen/symbiont relationship. Cellular physiology of both the partners is affected by abiotic stress. However, little is known about the degree of protection each offers to the other from different types of environmental stress. Our current study focused on the changes in response to toxic arsenic in the presence of an endophytic fungus Piriformospora indica that colonizes the paddy roots. The primary impact of arsenic was observed in the form of hyper-colonization of fungus in the host root and resulted in the recovery of its overall biomass, root damage, and chlorophyll due to arsenic toxicity. Further, fungal colonization leads to balance the redox status of the cell by adjusting the antioxidative enzyme system which in turn protects photosynthetic machinery of the plant from arsenic stress. We observed that fungus has ability to immobilize soluble arsenic and interestingly, it was also observed that fungal colonization restricts most of arsenic in the colonized root while a small fraction of it translocated to shoot of colonized plants. Our study suggests that P. indica protects the paddy (Oryza sativa) from arsenic toxicity by three different mechanisms viz. reducing the availability of free arsenic in the plant environment, bio-transformation of the toxic arsenic salts into insoluble particulate matter and modulating the antioxidative system of the host cell.

| S-EPMC5423915 | 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

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

The gut microbiome is required for full protection against acute arsenic toxicity in mouse models.

Project description:Arsenic poisons an estimated 200 million people worldwide through contaminated food and drinking water. Confusingly, the gut microbiome has been suggested to both mitigate and exacerbate arsenic toxicity. Here, we show that the microbiome protects mice from arsenic-induced mortality. Both antibiotic-treated and germ-free mice excrete less arsenic in stool and accumulate more arsenic in organs compared to control mice. Mice lacking the primary arsenic detoxification enzyme (As3mt) are hypersensitive to arsenic after antibiotic treatment or when derived germ-free, compared to wild-type and/or conventional counterparts. Human microbiome (stool) transplants protect germ-free As3mt-KO mice from arsenic-induced mortality, but protection depends on microbiome stability and the presence of specific bacteria, including Faecalibacterium. Our results demonstrate that both a functional As3mt and specific microbiome members are required for protection against acute arsenic toxicity in mouse models. We anticipate that the gut microbiome will become an important explanatory factor of disease (arsenicosis) penetrance in humans, and a novel target for prevention and treatment strategies.

| S-EPMC6303300 | biostudies-literature

The Herbal Constituents in An-Gong-Niu-Huang Wan (AGNH) Protect against Cinnabar- and Realgar-Induced Hepatorenal Toxicity and Accumulations of Mercury and Arsenic in Mice.

Project description:An-Gong-Niu-Huang Wan (AGNH) has been a well-known cinnabar- and realgar-containing compound recipe for cerebral diseases. Unfortunately, its clinical practice is often restrained by the specific hepatorenal toxicity of cinnabar and realgar (C + R). In previous research studies, we have found that the antioxidative and anti-inflammatory effects of its herbal constituents could mitigate the risks from the toxicity. The underlying detoxification mechanisms are still unsolved. The present study investigated the protective effects of AGNH's herbal constituents on hepatorenal injury induced by C + R. For the mice treated with C + R, the increased expression levels of sensitive biomarkers of metal exposure and hepatorenal toxicity, including metallothionein (MT) in both hepatorenal tissues and kidney induced molecule-1 (KIM-1) in the kidney, were simultaneously reduced when C + R coadministered with other herbal medicines. In addition, the contents of trivalent As (AsIII), pentavalent As (Asv), and mercury (Hg) in hepatorenal tissues of mice were also significantly reduced benefiting from the herbal constituents in AGNH. Further mechanism studies showed that the herbal constituents in AGNH could downregulate the expressions of uptake transporters (AQP9 and OAT1) and upregulate the expressions of efflux transporters (P-gp, MRP2, and MRP4) in mice intoxicated by C + R. Our results suggested that AGNH's herbal constituents protect the body against C + R-induced hepatorenal toxicity and accumulations of Hg and As, which could be associated with the reestablishment of heavy metal homeostasis and the detoxification system.

| S-EPMC8035015 | biostudies-literature

Bioaccumulation

Project description:Bioaccumulation experiment

| PRJEB20879 | ENA

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.

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| S-EPMC3569627 | biostudies-literature

Arsenic Toxicity: Molecular Targets and Therapeutic Agents.

Project description:: High arsenic (As) levels in food and drinking water, or under some occupational conditions, can precipitate chronic toxicity and in some cases cancer. Millions of people are exposed to unacceptable amounts of As through drinking water and food. Highly exposed individuals may develop acute, subacute, or chronic signs of poisoning, characterized by skin lesions, cardiovascular symptoms, and in some cases, multi-organ failure. Inorganic arsenite(III) and organic arsenicals with the general formula R-As2+ are bound tightly to thiol groups, particularly to vicinal dithiols such as dihydrolipoic acid (DHLA), which together with some seleno-enzymes constitute vulnerable targets for the toxic action of As. In addition, R-As2+-compounds have even higher affinity to selenol groups, e.g., in thioredoxin reductase that also possesses a thiol group vicinal to the selenol. Inhibition of this and other ROS scavenging seleno-enzymes explain the oxidative stress associated with arsenic poisoning. The development of chelating agents, such as the dithiols BAL (dimercaptopropanol), DMPS (dimercapto-propanesulfonate) and DMSA (dimercaptosuccinic acid), took advantage of the fact that As had high affinity towards vicinal dithiols. Primary prevention by reducing exposure of the millions of people exposed to unacceptable As levels should be the prioritized strategy. However, in acute and subacute and even some cases with chronic As poisonings chelation treatment with therapeutic dithiols, in particular DMPS appears promising as regards alleviation of symptoms. In acute cases, initial treatment with BAL combined with DMPS should be considered.

| S-EPMC7072575 | biostudies-literature

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