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1.
Biomed Pharmacother ; 141: 111923, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34328091

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Hipnóticos e Sedativos/farmacocinética , Ferro/farmacocinética , Locomoção/efeitos dos fármacos , Mercúrio/farmacocinética , Sono/efeitos dos fármacos , Animais , Animais não Endogâmicos , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/química , Feminino , Hipnóticos e Sedativos/análise , Hipnóticos e Sedativos/química , Ferro/análise , Ferro/química , Locomoção/fisiologia , Masculino , Mercúrio/análise , Mercúrio/química , Compostos de Mercúrio/análise , Compostos de Mercúrio/química , Compostos de Mercúrio/farmacocinética , Camundongos , Ratos , Ratos Wistar , Sono/fisiologia
2.
J Ethnopharmacol ; 250: 112489, 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-31866510

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Medicina Tradicional Chinesa/efeitos adversos , Compostos de Mercúrio/administração & dosagem , Síndromes Neurotóxicas/etiologia , Animais , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/farmacocinética , Medicamentos de Ervas Chinesas/toxicidade , Feminino , Rim/metabolismo , Fígado/metabolismo , Masculino , Compostos de Mercúrio/farmacocinética , Compostos de Mercúrio/toxicidade , Ratos , Ratos Sprague-Dawley , Medição de Risco , Distribuição Tecidual
3.
Neurotoxicol Teratol ; 66: 25-34, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29366690

RESUMO

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.


Assuntos
Comportamento Animal/efeitos dos fármacos , Ayurveda , Compostos de Mercúrio/toxicidade , Mercúrio/toxicidade , Atividade Motora/efeitos dos fármacos , Síndromes Neurotóxicas/fisiopatologia , Peixe-Zebra , Animais , Disponibilidade Biológica , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Feminino , Hidrocortisona/análise , Masculino , Mercúrio/farmacocinética , Compostos de Mercúrio/farmacocinética , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/metabolismo
4.
Biol Trace Elem Res ; 184(2): 536-545, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29130128

RESUMO

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.


Assuntos
Cisteína/farmacologia , Liberação Controlada de Fármacos/efeitos dos fármacos , Glutationa/farmacologia , Compostos de Mercúrio/farmacocinética , Mercúrio/farmacocinética , Disponibilidade Biológica , Suco Gástrico/química , Suco Gástrico/metabolismo , Trato Gastrointestinal/metabolismo , Concentração de Íons de Hidrogênio , Medicina Tradicional Tibetana , Mercúrio/química , Mercúrio/metabolismo , Compostos de Mercúrio/química , Compostos de Mercúrio/metabolismo , Água/química , Água/metabolismo
5.
Environ Pollut ; 213: 785-792, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-27038210

RESUMO

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.


Assuntos
Mergulho/fisiologia , Golfinhos/metabolismo , Glutationa/metabolismo , Mercúrio/análise , Metalotioneína/metabolismo , Selênio/análise , Poluentes Químicos da Água/análise , Animais , Biomarcadores/metabolismo , Brasil , Feminino , Inativação Metabólica , Fígado/metabolismo , Masculino , Mercúrio/farmacocinética , Compostos de Mercúrio/análise , Compostos de Mercúrio/farmacocinética , Compostos de Metilmercúrio/análise , Compostos de Metilmercúrio/farmacocinética , Músculos/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Selênio/farmacocinética , Compostos de Selênio/análise , Compostos de Selênio/farmacocinética , Oligoelementos/análise , Oligoelementos/farmacocinética , Poluentes Químicos da Água/farmacocinética
6.
Regul Toxicol Pharmacol ; 76: 51-6, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26804582

RESUMO

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.


Assuntos
Arsenicais/farmacocinética , Arsenitos/farmacocinética , Contaminação de Medicamentos , Medicamentos de Ervas Chinesas/farmacocinética , Cloreto de Mercúrio/farmacocinética , Compostos de Mercúrio/farmacocinética , Compostos de Sódio/farmacocinética , Sulfetos/farmacocinética , Administração Oral , Animais , Arsenicais/administração & dosagem , Arsenicais/urina , Arsenitos/administração & dosagem , Arsenitos/toxicidade , Arsenitos/urina , Disponibilidade Biológica , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/toxicidade , Fezes/química , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Cloreto de Mercúrio/administração & dosagem , Cloreto de Mercúrio/toxicidade , Cloreto de Mercúrio/urina , Compostos de Mercúrio/administração & dosagem , Compostos de Mercúrio/toxicidade , Compostos de Mercúrio/urina , Ratos Sprague-Dawley , Medição de Risco , Compostos de Sódio/administração & dosagem , Compostos de Sódio/toxicidade , Compostos de Sódio/urina , Sulfetos/administração & dosagem , Sulfetos/toxicidade , Sulfetos/urina , Distribuição Tecidual
7.
Zhongguo Zhong Yao Za Zhi ; 40(12): 2455-60, 2015 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-26591542

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas/farmacocinética , Trato Gastrointestinal/metabolismo , Compostos de Mercúrio/farmacocinética , Animais , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/química , Rim/metabolismo , Fígado/metabolismo , Masculino , Mercúrio/química , Mercúrio/farmacocinética , Compostos de Mercúrio/química , Camundongos , Solubilidade
8.
Environ Res ; 143(Pt A): 55-61, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26436307

RESUMO

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.


Assuntos
Golfinhos/metabolismo , Mercúrio/farmacocinética , Músculos/metabolismo , Selênio/farmacocinética , Animais , Microanálise por Sonda Eletrônica , Monitoramento Ambiental , Feminino , Masculino , Compostos de Mercúrio/farmacocinética , Compostos de Metilmercúrio/farmacocinética , Compostos de Selênio/farmacocinética , Especificidade da Espécie , Poluentes Químicos da Água/farmacocinética , Espectroscopia por Absorção de Raios X
9.
Sci Total Environ ; 454-455: 9-15, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23538135

RESUMO

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

Assuntos
Monitoramento Ambiental/métodos , Trato Gastrointestinal/metabolismo , Materia Medica/farmacocinética , Ayurveda , Compostos de Mercúrio/farmacocinética , Disponibilidade Biológica , Humanos , Índia , Materia Medica/análise , Compostos de Mercúrio/análise , Extratos Vegetais/análise , Extratos Vegetais/farmacocinética , Medição de Risco/métodos , Espectrometria por Raios X , Espectroscopia por Absorção de Raios X
10.
Zhongguo Zhong Yao Za Zhi ; 37(6): 750-3, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22715715

RESUMO

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.


Assuntos
Medicamentos de Ervas Chinesas/uso terapêutico , Liliaceae/química , Compostos de Mercúrio/farmacocinética , Intoxicação por Mercúrio/prevenção & controle , Plantas Medicinais/química , Mucosa Gástrica/metabolismo , Humanos , Inativação Metabólica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Medicina Tradicional Chinesa , Compostos de Mercúrio/efeitos adversos , Compostos de Mercúrio/uso terapêutico , Rizoma/química , Estômago/efeitos dos fármacos
11.
Toxicol Lett ; 200(3): 194-200, 2011 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-21126564

RESUMO

Cinnabar (HgS) is used in traditional medicines, and total Hg content is used for risk assessment of cinnabar-containing traditional medicines such as Zhu-Sha-An-Shen-Wan (ZSASW). Is ZSASW or cinnabar toxicologically similar to common mercurials? Adult Sprague-Dawley rats were gavaged with ZSASW (1.4 g/kg), cinnabar (0.2g/kg), HgCl(2) (0.02 g/kg), MeHg (0.001 g/kg), or saline daily for 60 days, and toxicity was determined. Animal body-weight gain was decreased by HgCl(2) and MeHg. Blood urea nitrogen (BUN) was increased by MeHg. Histology showed severe kidney injury following MeHg and HgCl(2) treatments, but mild after ZSASW and cinnabar. Renal Hg contents were markedly increased in the HgCl(2) and MeHg groups but were not elevated in the ZSASW and cinnabar groups. The expression of kidney injury molecule-1 was increased 50-fold by MeHg, 4-fold by HgCl(2), but was unaltered by ZSASW and cinnabar; the expression of matrilysin was increased 3-fold by MeHg. In contrast, the expression of N-cadherin was decreased by HgCl(2). Thus, ZSASW and cinnabar are much less nephrotoxic than HgCl(2) and MeHg, indicating that chemical forms of mercury underlie their disposition and toxicity.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Cloreto de Mercúrio/toxicidade , Compostos de Mercúrio/toxicidade , Compostos de Metilmercúrio/toxicidade , Animais , Biomarcadores/metabolismo , Análise Química do Sangue , Peso Corporal/efeitos dos fármacos , Primers do DNA , Expressão Gênica/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Nefropatias/induzido quimicamente , Nefropatias/patologia , Masculino , Medicina Tradicional Chinesa , Cloreto de Mercúrio/farmacocinética , Mercúrio/metabolismo , Compostos de Mercúrio/farmacocinética , Intoxicação por Mercúrio/genética , Intoxicação por Mercúrio/patologia , Compostos de Metilmercúrio/farmacocinética , RNA/genética , RNA/isolamento & purificação , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Aumento de Peso/efeitos dos fármacos
12.
Chem Biol Interact ; 189(1-2): 134-40, 2011 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21094152

RESUMO

An-gong-niu-huang wan (AGNH) is a famous traditional Chinese medicine used for brain trauma, hemorrhage, and coma. AGNH contains 10% realgar (As4S4) and 10% cinnabar (HgS). Both As and Hg are well-known for their toxic effects, and the safety of AGNH is of concern. To address this question, the acute toxicity of AGNH, realgar and cinnabar were compared to sodium arsenite (NaAsO2) and mercuric chloride (HgCl2). Mice were administrated orally AGNH at 1, 3 and 6g/kg. AGNH at 3g/kg contains 2.8mmol As/kg as realgar and 1.18mmol Hg/kg as cinnabar. Realgar, cinnabar, arsenite (0.28 mmol/kg, 10% of realgar) and HgCl2 (0.256 mmol/kg, 20% of cinnabar) were orally given to mice for comparison. Blood and tissues were collected 8h later for toxicity evaluation. Serum alanine aminotransferase was increased by arsenite and blood urea nitrogen was increased by HgCl2. Total As accumulation after arsenite in liver (100-fold) and kidney (13-fold) was much higher than that after realgar. The accumulation of Hg after HgCl2 in liver was 400-fold higher and kidney 30-fold higher than after cinnabar. Histopathology showed moderate liver and kidney injuries after arsenite and HgCl2, but injuries were mild or absent after AGNH, realgar, and cinnabar. The expression of metallothionein-1, a biomarker of metal exposure, was increased 4-10-fold by arsenite and HgCl2, but was unchanged by AGNH, realgar and cinnabar. Thus, AGNH, realgar and cinnabar are much less toxic acutely than arsenite and HgCl2. The chemical forms of As and Hg are extremely important factors in determining their disposition and toxicity.


Assuntos
Medicina Tradicional Chinesa , Compostos de Mercúrio/toxicidade , Sulfetos/toxicidade , Alanina Transaminase/sangue , Animais , Arsênio/farmacocinética , Arsenicais/farmacocinética , Arsenitos/farmacocinética , Arsenitos/toxicidade , Aspartato Aminotransferases/sangue , Nitrogênio da Ureia Sanguínea , Creatinina/sangue , Feminino , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Cloreto de Mercúrio/farmacocinética , Cloreto de Mercúrio/toxicidade , Mercúrio/farmacocinética , Compostos de Mercúrio/farmacocinética , Metalotioneína/biossíntese , Metalotioneína/genética , Camundongos , RNA Mensageiro/biossíntese , RNA Mensageiro/genética , Distribuição Aleatória , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Compostos de Sódio/farmacocinética , Compostos de Sódio/toxicidade , Sulfetos/farmacocinética
13.
Zhongguo Zhong Yao Za Zhi ; 34(23): 3068-72, 2009 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-20222426

RESUMO

OBJECTIVE: To investigate the mercury cumulation following single dose or long-term use of Cinnabar to rats. METHOD: The Cinnabar which was used in the study contains 98% insoluble mercuric sulfide (HgS) and 21.5 mg x kg(-1) soluble mercuric compounds. Two separate experiments were performed: (1) Tweenty-eight fasting SD rats were orally given a single dose of Cinnabar at the dose of 0.8 g x kg(-1) and the other four rats were given ultra-filtrated water served as control group. Blood, livers, kidneys and brains of four rats were taken out at 0.5, 1, 2, 4, 8, 16, 36 h respectively after treatment. Mercury quantity of each organ or blood sample was measured. (2) Forty SD rats were randomly divided into four groups: control group and Cinnabar 0.1, 0.4, 0.8 g x kg(-1) groups, each group containing 5 females and 5 males. The rats were intra-gastrically treated with Cinnabar once a day for successively 90 days, while the control group was given ultra-filtrated water. Mercury contents in blood, livers, kidneys and brain of each rat were measured at 16 h of fasting after last dosing. RESULT: Mercury contents of blood, liver, kidney and brain increased slightly after single dosing of Cinnabar at dose of 0.8 g x kg(-1), with the order from high to low liver > blood > brain > kidney. Whereas 90-day oral treatment of Cinnabar led to significant cumulation of mercury in organs but not in blood. Kidney' s cumulation of mercury was much higher than any other tested organs and blood. Brain's mercury cumulation was also very high. The contents of mercury in kidney and brain of 0.8 g x kg(-1) group (total intake of soluble mercury within 90 days was 1 548 microg x kg(-1)) were respectively 71.2 and 27.4 times higher than control group. Even though in the lowest dose 0.1 g x kg(-1) group (total intake of soluble mercury 194 microg? kg(-1)), the mercury cumulation folds in kidney and brain were 16.77 and 20.43 respectively. However, liver got lower mercury cumulation than kidney and brain, which led to only 2 folds mercury cumulation at dose of 0.8 g x kg(-1). Our previous study showed that 90-day administration of Cinnabar at the dose > or = 0.1 g x kg(-1) (total intake of soluble mercury 194 microg x kg(-1)) could cause pathological changes in kidney and liver, indicating both were the toxicity targets for Cinnabar. Those manifested that liver could be more sensitive than kidney to mercury. Though brain got 20 times mercury cumulation after 90 day treatment, the animals showed no abnormal signs in general behavior and brain histomorphology,which indicated that rat brain was not sensitive to mercury. CONCLUSION: Soluble mercury in Cinnabar can be absorbed causing high cumulated in some organs, such as kidney and brain after long-term use of Cinnabar. Liver had also mercury cumulation, but was much lower than kidney. Total intake of soluble mercury for > or = 194 microg x kg(-1) within 90 days could cause toxicosis by mercury cumulation.


Assuntos
Compostos de Mercúrio/farmacocinética , Administração Oral , Animais , Encéfalo/metabolismo , Feminino , Rim/metabolismo , Fígado/metabolismo , Masculino , Mercúrio/farmacocinética , Compostos de Mercúrio/administração & dosagem , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
14.
Arch Toxicol ; 82(6): 343-53, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18049810

RESUMO

This study is aimed at exploring the possible mechanism of hypnosis-enhancing effect of HgS or cinnabar (a traditional Chinese medicine containing more than 95% HgS) in mice treated with pentobarbital. We also examined whether the effect of HgS is different from that of the well-known methyl mercury (MeHg). After a short period (7 days) of oral administration to mice, a nontoxic dose (0.1 g/kg) of HgS not only significantly enhanced pentobarbital-induced hypnosis but also attenuated tolerance induction; while a higher dose (1 g/kg) of HgS or cinnabar exerted an almost irreversible enhancing effect on pentobarbital-hypnosis similar to that of MeHg (2 mg/kg) tested, which was still effective even after 10 or 35 days cessation of administration. To study comparatively the effects of different mercury forms from oral administration of MeHg and HgS on membrane ATPase activities of experimental mice, analysis of the Hg content in the cerebral cortex revealed that correlated with the decrease of Na(+)/K(+)-ATPase and Ca(2+)-ATPase activities. Furthermore, NO levels of blood but not that of cerebral cortex were also decreased by mercuric compounds. Although pentobarbital alone enhanced cytochrome p450-2C9 in time dependent manner, all of mercurial compounds tested had no such effect. All of these findings indicated that the mercurial compounds including cinnabar, HgS and MeHg exert a long-lasting enhancing hypnotic activity without affecting pentobarbital metabolism, which provides evidence-based sedative effect of cinnabar used in Chinese traditional medicine for more than 2,000 years. The nontoxic HgS dosing (0.1 g/kg/day) for consecutive 7 days is perhaps useful for delaying or preventing pentobarbital-tolerance.


Assuntos
Adenosina Trifosfatases/metabolismo , Córtex Cerebral/efeitos dos fármacos , Hipnóticos e Sedativos/farmacologia , Compostos de Mercúrio/toxicidade , Compostos de Metilmercúrio/toxicidade , Óxido Nítrico/metabolismo , Fenobarbital/farmacologia , Adenosina Trifosfatases/antagonistas & inibidores , Administração Oral , Animais , ATPases Transportadoras de Cálcio/antagonistas & inibidores , ATPases Transportadoras de Cálcio/metabolismo , Córtex Cerebral/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Modelos Animais de Doenças , Sinergismo Farmacológico , Tolerância a Medicamentos , Fígado/efeitos dos fármacos , Fígado/enzimologia , Masculino , Compostos de Mercúrio/farmacocinética , Compostos de Metilmercúrio/farmacocinética , Camundongos , Sono/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/antagonistas & inibidores , ATPase Trocadora de Sódio-Potássio/metabolismo
15.
Toxicol Appl Pharmacol ; 224(2): 192-201, 2007 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-17707451

RESUMO

Cinnabar, a naturally occurring mercuric sulfide (HgS), has long been used in combination with traditional Chinese medicine as a sedative for more than 2000 years. Up to date, its pharmacological and toxicological effects are still unclear, especially in clinical low-dose and long-term use. In this study, we attempted to elucidate the effects of cinnabar on the time course of changes in locomotor activities, pentobarbital-induced sleeping time, motor equilibrium performance and neurobiochemical activities in mice during 3- to 11-week administration at a clinical dose of 10 mg/kg/day. The results showed that cinnabar was significantly absorbed by gastrointestinal (G-I) tract and transported to brain tissues. The spontaneous locomotor activities of male mice but not female mice were preferentially suppressed. Moreover, frequencies of jump and stereotype-1 episodes were progressively decreased after 3-week oral administration in male and female mice. Pentobarbital-induced sleeping time was prolonged and the retention time on a rotating rod (60 rpm) was reduced after treatment with cinnabar for 6 weeks and then progressively to a greater extent until the 11-week experiment. In addition, the biochemical changes in blood and brain tissues were studied; the inhibition of Na(+)/K(+)-ATPase activities, increased production of lipid peroxidation (LPO) and nitric oxide (NO) were found with a greater extent in male mice than those in female mice, which were apparently correlated with their differences in the neurological responses observed. In conclusion, these findings, for the first time, provide evidence of the pharmacological and toxicological basis for understanding the sedative and neurotoxic effects of cinnabar used as a Chinese mineral medicine for more than 2000 years.


Assuntos
Medicamentos de Ervas Chinesas/toxicidade , Compostos de Mercúrio/toxicidade , Óxido Nítrico/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Feminino , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Compostos de Mercúrio/farmacocinética , Camundongos , Camundongos Endogâmicos ICR , Atividade Motora/efeitos dos fármacos , Pentobarbital , Equilíbrio Postural/efeitos dos fármacos , Fatores Sexuais , Sono/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/efeitos dos fármacos , ATPase Trocadora de Sódio-Potássio/metabolismo , Fatores de Tempo , Distribuição Tecidual
16.
Crit Care ; 7(3): R1-6, 2003 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-12793883

RESUMO

INTRODUCTION: Inorganic mercury poisoning is uncommon, but when it occurs it can result in severe, life-threatening features and acute renal failure. Previous reports on the use of extracorporeal procedures such as haemodialysis and haemoperfusion have shown no significant removal of mercury. We report here the successful use of the chelating agent 2,3-dimercaptopropane-1-sulphonate (DMPS), together with continuous veno-venous haemodiafiltration (CVVHDF), in a patient with severe inorganic mercury poisoning. CASE REPORT: A 40-year-old man presented with haematemesis after ingestion of 1 g mercuric sulphate and rapidly deteriorated in the emergency department, requiring intubation and ventilation. His initial blood mercury was 15 580 microg/l. At 4.5 hours after ingestion he was started on DMPS. He rapidly developed acute renal failure and so he was started on CVVHDF for renal support and in an attempt to improve mercury clearance; CVVHDF was continued for 14 days. METHODS: Regular ultradialysate and pre- and post-filtrate blood samples were taken and in addition all ultradialysate generated was collected to determine its mercury content. RESULTS: The total amount of mercury in the ultrafiltrate was 127 mg (12.7% of the ingested dose). The sieving coefficient ranged from 0.13 at 30-hours to 0.02 at 210-hours after ingestion. He developed no neurological features and was discharged from hospital on day 50. Five months after discharge from hospital he remained asymptomatic, with normal creatinine clearance. DISCUSSION: We describe a patient with severe inorganic mercury poisoning in whom full recovery occurred with the early use of the chelating agent DMPS and CVVHDF. There was removal of a significant amount of mercury by CVVHDF. CONCLUSION: We feel that CVVHDF should be considered in patients with inorganic mercury poisoning, particularly those who develop acute renal failure, together with meticulous supportive care and adequate doses of chelation therapy with DMPS.


Assuntos
Hemodiafiltração/métodos , Compostos de Mercúrio/intoxicação , Intoxicação por Mercúrio/terapia , Sulfatos/intoxicação , Unitiol/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/terapia , Adulto , Seguimentos , Gastrite/induzido quimicamente , Gastrite/terapia , Hematemese/induzido quimicamente , Hematemese/terapia , Humanos , Masculino , Compostos de Mercúrio/farmacocinética , Taxa de Depuração Metabólica , Úlcera Gástrica/induzido quimicamente , Úlcera Gástrica/terapia , Tentativa de Suicídio , Sulfatos/farmacocinética , Resultado do Tratamento
17.
Zhongguo Zhong Yao Za Zhi ; 28(7): 639-42, 2003 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-15139110

RESUMO

OBJECTIVE: To study comparatively the characteristics of absorption and distribution of mercury and arsenic from realgar and cinnabar of Angong Niuhuang Pill in normal rats and the rats with cerebral ischemia after oral administration. METHOD: The blood samples and homogenates of liver, kidney and brain were prepared at various intervals after the animals were treated with Angong Niuhuang pill ig. The levels of total mercury and total arsenic in the blood and the organ homogenates were measured with Microwava Accelerated Reaction System and AAs, respectively. RESULT: The blood concentrations of mercury and arseic reached the highest point in normal rats at one hour following single oral dosing of Angong Niuhuang pill. In normal rats, the mercury distribution was characterized by its higher level in blood and kidneys than in other organs, while a higher distribution of arsenic was found in blood than in organs. No difference in the distribution of mercury or arsenic was found between normal rats and rats with cerebral ischemia after the treatment with the pill. CONCLUSION: The highest level of mercury or arsenic in blood occurs at one hour after oral administration of the pill in normal rats. There is a higher distribution of mercury in blood and kidneys, while a higher distribution of the arsenic only in blood. There is no significant difference in the distribution of mercury or arsenic between the normal rats and the ischemic rats.


Assuntos
Arsenicais/farmacocinética , Isquemia Encefálica/metabolismo , Medicamentos de Ervas Chinesas/farmacocinética , Materia Medica/farmacocinética , Compostos de Mercúrio/farmacocinética , Sulfetos/farmacocinética , Animais , Arsênio/sangue , Arsênio/metabolismo , Combinação de Medicamentos , Medicamentos de Ervas Chinesas/isolamento & purificação , Masculino , Materia Medica/isolamento & purificação , Mercúrio/sangue , Mercúrio/metabolismo , Plantas Medicinais/química , Ratos , Distribuição Tecidual
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