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PubMed2004

Association of clinical complications with nutritional status and the prevalence of leukopenia among arsenic patients in Bangladesh.

This study conducted in Bangladesh reports the relationship of clinical complications with nutritional status and the prevalence of leukopenia among arsenic exposed patients living in the rural villages. A total of 115 exposed individuals diagnosed as arsenicosis patients were randomly selected from four known arsenic endemic villages, and age-matched 120 unexposed subjects were enrolled in the study program. The duration of arsenic exposure in about 37% of the patients was at least 10 yrs, while the population mean and range were 7.6 +/- 5.2 yrs, and 1 - 25 yrs, respectively. The mean arsenic concentrations in the drinking water for the exposed and unexposed (control) population were 218.1 microg/L and 11.3 microg/L, respectively. The spot urine sample of the arsenicosis patients contained an average of 234.6 microg/L arsenic. Although very few patients showed elevated WBC count, 16% had leukopenia (below normal count), and the whole population had significantly low WBC count than the control subjects. Prevalences of neutropenia and lymphocytosis were observed in patients with chronic exposure to high levels of arsenic in water. The body mass index was found to be lower than 18.5, the cut-off point for malnutrition (underweight), in about 28% of the arsenicosis cases compared to 15% of the controls. The monthly income and total calorie consumption per day showed the patients were underprivileged than the controls. Arsenical symptoms and complications were more severe in the nutritionally vulnerable (underweight) patients than the overweight ones. Also, the incidences of leukopenia and anaemia were more common in the female patients who were underweight. The findings of this research demonstrate that the poor nutritional status of patients increases the complications of chronic arsenic toxicity; suggest the possibility of other sources of arsenic contamination different from drinking water in the study area; and establish a higher prevalence of leukopenia and lymphocytosis in arsenicosis patients.

Adolescent↗
PubMed1981

A rapid method for the selective analysis of total urinary metabolites of inorganic arsenic.

Total urinary arsenic has traditionally been used for assessing occupational exposure to inorganic arsenic. However, dietary arsenic, especially from seafood, may greatly influence this value. This paper describes a fast and convenient method for routinely measuring the combined amount of inorganic arsenic, methylarsonic acid, and dimethylarsinic acid, which are the major urinary metabolites after exposure to inorganic arsenic. Organic arsenic compounds of marine origin are not biotransformed to inorganic arsenic or methylated arsenic acids to any significance in the human body. They do not produce arsines when treated with the reducing agent in the proposed method and will therefore not interfere with the measurements. The sensitivity, accuracy, and precision of the proposed method are sufficient for the determination of concentrations of arsenic normally found in the urine of nonexposed persons. The method is based on a commercially available hydride generation kit attached to an atomic absorption spectrophotometer.

Arsenic↗
PubMed2001

Arsenic and liver disease.

The hepatotoxic action of arsenic, when used as a therapeutic agent, has long been recognised. Data on liver involvement following chronic exposure to arsenic-contaminated water are scanty. The nature and degree of liver involvement are reported on the basis of hospital based studies in patients who consumed arsenic contaminated drinking water for one to 15 years. Two hundred forty-eight patients with evidence of chronic arsenic toxicity underwent clinical and laboratory examination including liver function tests and hepatitis B surface antigen (HBsAg) status. Liver biopsy was done in 69 cases; in 29 patients, liver arsenic content was estimated by neutron activation analysis. Hepatomegaly was present in 190 of 248 patients (76.6%). Non-cirrhotic portal fibrosis was the predominant lesion (91.3%) in liver histology. The maximum arsenic content in liver was 6 mg/kg (mean 1.46 [0.42], control value 0.16 [0.04]; p <0.001); it was undetected in 6 of 29 samples studied. The largest number of patients with liver disease due to chronic arsenicosis from drinking arsenic contaminated water are reported. Non-cirrhotic portal fibrosis is the predominant lesion in this population. Hepatic fibrosis has also been demonstrated due to long term arsenic toxicity in an animal model. Initial biochemical evidence of hepatic membrane damage, probably due to reduction of glutathione and antioxidant enzymes, may be seen by 6 months. Continued arsenic feeding resulted in fatty liver with serum aminotransferases elevated at 12 months and hepatic fibrosis at 15 months.

Adult↗
PubMed2002

Mechanisms of action of arsenic trioxide.

Arsenic trioxide has shown substantial efficacy in treating both newly diagnosed and relapsed patients with acute promyelocytic leukemia (APL). As a single agent, it induces complete remissions, causing few adverse effects and only minimal myelosuppression. These successes have prompted investigations to elucidate the mechanisms of action underlying these clinical responses. Substantial data show that arsenic trioxide produces remissions in patients with APL at least in part through a mechanism that results in the degradation of the aberrant PML-retinoic acid receptor alpha fusion protein. Studies have also investigated concerns about the toxicity and potential carcinogenicity of long-term exposure to environmental arsenic. Arsenic apparently affects numerous intracellular signal transduction pathways and causes many alterations in cellular function. These actions of arsenic may result in the induction of apoptosis, the inhibition of growth and angiogenesis, and the promotion of differentiation. Such effects have been observed in cultured cell lines and animal models, as well as clinical studies. Because arsenic affects so many cellular and physiological pathways, a wide variety of malignancies, including both hematologic cancer and solid tumors derived from several tissue types, may be susceptible to therapy with arsenic trioxide. These multiple actions of arsenic trioxide also highlight the need for additional mechanistic studies to determine which actions mediate the diverse biological effects of this agent. This information will be critical to realizing the potential for synergy between arsenic trioxide and other chemotherapeutic agents, thus providing enhanced benefit in cancer therapy.

Animals↗
PubMed2004

Combined effect of arsenic trioxide and sulindac sulfide in A549 human lung cancer cells in vitro.

Arsenic trioxide has shown substantial efficacy in treating patients with relapsed or refractory acute promyelocytic leukemia (APL) as well as solid tumors. Arsenic can act through a considerable number of different pathways including mitochondrial respiration and tubulin formation, affecting growth, blood flow, differentiation, and apoptosis. Recent studies on the apoptotic potential of arsenic trioxide have elucidated some of its causal mechanisms, including elevation of intracellular H2O2, inhibition of NF-kappaB activity, and inhibition of GTP-induced polymerization of tubulin. Because of the variety in cellular approaches available to arsenic, it has been hypothesized that the combination of arsenic trioxide and other chemotherapeutic agents may result in cytotoxic synergy. Recent studies have proven this true, with all-trans retinoic acid, IFN-alpha, and ascorbic acid all yielding promising results when used in conjunction with arsenic trioxide. In this study we tested sulindac sulfide, a nonsteroidal anti-inflammatory drug (NSAID) to test its effects with arsenic. Sulindac was used because it functions by some of the same pathways as arsenic, including the mitochondrial apoptotic pathway and the NF-kappaB pathway. Our results show that sulindac sulfide enhances cytotoxicity when combined with arsenic trioxide, and that further studies on the exact mechanisms of their interaction are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2005

[The effect and mechanism of arsenic trioxide on hepatocellular carcinoma].

OBJECTIVE: To investigate the effect and mechanism of arsenic trioxide on hepatoma cell line BEL-7402 and observe the effect and best administration method of arsenic trioxide on hepatocellular carcinoma patients who were not suitable for operation. METHODS: The cell activity and morphologic changes were studied after being treated with arsenic trioxide in different concentrations. The apoptosis was detected by flow cytometry assay and DNA fragmentation assay. The caspase-3 level of mRNA and protein were detected by reverse transcription polymerase chain reaction (RT-PCR) and fluoro-spectrophotometer. The growth inhibition of implant tumor was observed in nude mice treated with arsenic trioxide in different concentrations. Arsenic trioxide was used in hepatocellular carcinoma patients by intravenous dropping and continuous regional infusion through hepatic artery. RESULTS: The effect of arsenic trioxide on hepatoma cell lines was dependent on the time and concentration obviously. The decrease in cell number was preceded by morphological changes in the treated BEL-7402 cells that were characteristic of apoptosis, including membrane blebbing, shrunken cytoplasm, nuclear condensation and loss of adhesion. Flow cytometry assay showed an arrestment at G(2)/M phase and sub-G(1) cell peak. DNA fragmentation assay showed a marked DNA ladder. The mRNA level of caspase-3 was no change in RT-PCR whereas the protein of caspase-3 was increased after added As(2)O(3) 1 - 36 h. Caspase-3 activity began to increase after 2 h and reached a maximal level after 12 h in a linear fashion. Then, the level of caspase-3 was decreased, but still in a high level. The growth inhibition of implant tumors was obviously in nude mice. The intravenous usage of arsenic trioxide could improve the quality of life with low toxicity in hepatocellular carcinoma patients not suitable for operation. The tumor size decreased in 30 patients and AFP value decreased in 19 patients by continuous regional infusion through hepatic artery. CONCLUSIONS: Arsenic trioxide can obviously inhibit the growth of hepatoma cell line BEL-7402 through inducing hepatoma cell apoptosis. The activation and increase of Caspase-3 is the possible mechanism of apoptosis, and the acting point is in pro-enzyme level. The best result of arsenic trioxide on non-operative patients should be gotten in continuous infusion through hepatic artery.

Adult↗
PubMed2005

Absorption and metabolism of paracetamol in rats drinking high concentration of arsenic.

The effect of chronic intake of arsenic on the plasma concentration of paracetamol in rat was investigated. Rats received saline water with or without arsenic trioxide (10 mg/kg body weight/day) by gastric gavage on every alternate day for 29 days. A single dose of paracetamol (range 10 infinity 40 mg/kg body weight) was administered by gastric gavage to both arsenic-untreated and -treated rats on 30(th) day. Rats were sacrificed after 30 min and the amounts of free paracetamol and its metabolites in plasma were estimated using isocratic reverse-phase High Performance Liquid Chromatography (HPLC). Arsenic toxicity reduced the plasma concentration of paracetamol to 53 - 65% when compared with the rats received no added arsenic. There were maximum 67.4 and 76.9% inhibitions of sulfate and cysteine conjugations of paracetamol respectively. But arsenic had no effect on glucuronide and mercapturate conjugations. Both liver and small intestine showed increased accumulation of arsenic and decreased amount of glutathione in arsenic-treated rats. This study suggests that chronic ingestion of arsenic inhibit the absorption and metabolism of paracetamol.

Acetaminophen↗
PubMed2004

Effects of protein deficient diets on the developmental toxicity of inorganic arsenic in mice.

BACKGROUND: Inorganic arsenic, when given by injection to pregnant laboratory animals (mice, rats, hamsters), has been shown to induce malformations. Arsenic methylation may be a detoxification step, and diets deficient in protein are a poor source of methyl donors and may possibly result in impaired arsenic methylation. Human health effects from chronic arsenic exposure have been reported mainly in populations with low socioeconomic status. Individuals in such populations are likely to suffer from malnutrition, which can compromise embryonic/fetal development and diminish arsenic methylating capacity. We sought to determine if dietary protein deficiency affects the developmental toxicity of inorganic arsenic. METHODS: Mated females were randomly assigned to one of 12 treatment groups. Experimental groups received either AsIII or AsV i.p. on Gestation Day 8 (GD 8, plug=GD 0) and were maintained on a 5%, 10%, or 20% protein custom mixed diet from GD 1 until sacrifice. Controls received the custom diets alone, were given AsIII or AsV i.p. on GD 8 with Teklad LM-485 rodent diet, or were fed the LM-485 diet alone. Test females were sacrificed on GD 17, and their litters were examined for mortality and developmental defects. RESULTS: Arsenic plus dietary protein deficiency decreased maternal weight gain and increased the incidences of exencephaly, ablepharia, and skeletal defects, such as malformed vertebral centra, fused ribs, and abnormal sternebrae (bipartite, rudimentary, or unossified). CONCLUSIONS: These results demonstrate that dietary protein deficiency enhances the developmental toxicity of inorganic arsenic, possibly by impairment of arsenic methylation.

Abnormalities, Drug-Induced↗
PubMed2002

Arsenic induces oxidative stress and activates stress gene expressions in cultured lung epithelial cells.

Chronic exposure to low levels of arsenic can cause lung cancer. However, the cellular and molecular mechanisms for lung cell transformation in response to arsenic are not known. These studies investigated the hypothesis that low levels of arsenic increase intracellular oxidant levels, promote production of mitogenic transcription factors and antioxidant enzymes. Initially, arsenic decreased GSH cellular level and rapidly increased to 280% of GSH level in nonexposed lung cells in 24 h. Buthionine sulfoximine (BSO) potentiated the arsenic toxicity of lung epithelial cells (LEC). Exposure of LEC to 5 microM arsenite cause time-dependent increase in gamma-glutamylcysteine synthetase (gamma-GCS) expression. Our data demonstrated that arsenic induced the heavy subunit of gamma-GCS (gamma-GCS-HS) mRNA levels as early as 4 h as compared to the control level. It significantly increased (sixfolds) gamma-GCS-HS mRNA expression after 8 h of treatment. The activation of AP-1 transcription factors may also play a regulatory role in this process. Significant elevations in c-fos and c-jun mRNA levels were observed within 30 min after exposure to arsenic and by enhancement of AP-1 DNA binding activity and transactivation activity. Responsiveness of LEC to oxidative stress caused by arsenic exposure was further evaluated with mobility shift assay involving redox-sensitive transcription factor NF-kappa B. The specificity of binding was verified by an antibody-supershift. The NF-kappa B DNA binding activities increased more than twofold 30 min after exposure to arsenic and returned to control levels after 4 h of treatment. It remains to be determined whether NF-kappa B plays a role in the As-induced apoptosis or alternatively in attempting to protect the cells from As-induced cell death by upregulating the expression of resistance factors.

Animals↗
PubMed1995

Investigation of arsenic exposure from soil at a superfund site.

The purpose of this study was to determine if significant arsenic exposure was occurring at a Superfund site with elevated surface soil arsenic concentrations. A second objective was to determine the statistical relationship between the various methods of measuring arsenic exposure in humans. Random urine, 24-hr urine, hair, and fingernail samples were collected at the end of the workweek from 40 employees at an active pesticide manufacturing facility which had formerly produced arsenical pesticides. There was no indication of adverse health effects among the employees attributable to arsenic exposure. Mean urinary, hair, and fingernail concentrations of arsenic were well within normal values and indicated that significant arsenic exposure was not occurring among the employees. Random and 24-hr urine measurements were significantly correlated. Hair and fingernail results also were significantly correlated. Urine results did not correlate well with hair or fingernail results. Results of this study suggest that although there may be some individual variation, random and 24-hr urine arsenic results are not substantially different. For the purpose of screening for arsenic exposure, random urine samples may be an adequate and preferable test for those populations in equilibrium with their environment.

Arsenic↗
PubMed2001

Determination of trivalent methylated arsenicals in biological matrices.

The enzymatically catalyzed oxidative methylation of As yields methylated arsenicals that contain pentavalent As (As(V)). Because trivalent As (As(III)) is the favored substrate for this methyltransferase, methylated arsenicals containing As(V) are reduced to trivalency in cells. Methylated arsenicals that contain As(III) are extremely potent inhibitors of NADPH-dependent flavoprotein oxidoreductases and potent cytotoxins in many cell types. Therefore, the formation of methylated arsenicals that contain As(III) may be properly regarded as an activation step, rather than a means of detoxification. Recognition of the role of methylated arsenicals that contain As(III) in the toxicity and metabolism of As emphasizes the need for analytical methods to detect and quantify these species in biological samples. Hence, a method was developed to exploit pH-dependent differences in the generation of arsines from inorganic and methylated arsenicals that contain either As(V) or As(III). Reduction with borohydride at pH 6 generated arsines from inorganic As(III), methyl As(III), and dimethyl As(III), but not from inorganic As(V), methyl As(V), and dimethyl As(V). Reduction with borohydride at pH 2 or lower generated arsines from arsenicals that contained either As(V) or As(III). Arsines are trapped in a liquid nitrogen-cooled gas chromatographic trap, which is subsequently warmed to allow separation of the hydrides by their boiling points. Atomic absorption spectrophotometry is used to detect and quantify the arsines. The detection limits (ng As ml(-1)) for inorganic As(III), methyl As(III), and dimethyl As(III) are 1.1, 1.2, and 6.5, respectively. This method has been applied to the analysis of arsenicals in water, human urine, and cultured cells. Both methyl As(III) and dimethyl As(III) are detected in urine samples from individuals who chronically consumed inorganic As-contaminated water and in human cells exposed in vitro to inorganic As(III). The reliable quantitation of inorganic and methylated arsenicals that contain As(III) in biological samples will aid the study of the toxicity of these species and may provide a new biomarker of the effects of chronic exposure to As.

Arsenicals↗
PubMed1994

Diethyl maleate, an in vivo chemical depletor of glutathione, affects the response of male and female rats to arsenic deprivation.

An experiment was performed to determine the effect of diethyl maleate (DEM), an in vivo depletor of glutathione, on the response of male and female rats to arsenic deprivation. A 2 x 2 x 2 factorially arranged experiment used groups of six weanling Sprague-Dawley rats. Dietary variables were arsenic at 0 or 0.5 microgram/g and DEM at 0 or 0.25%; the third variable was gender. Animals were fed for 10 wk a casein-ground corn based diet that contained amounts of calcium, phosphorus, and magnesium similar to the AIN-76 diet. DEM supplementation increased blood arsenic in both male and female rats; female rats had the greatest amount of arsenic in whole blood. Although female rats in general had a lower concentration of glutathione in liver, those fed no supplemental DEM, regardless of their arsenic status, had the lowest amounts. Compared to males, female rats had a lower activity of liver glutathione S-transferase (GST). Arsenic deprivation decreased, and DEM supplementation increased liver GST activity in both male and female rats. Lung GST activity was also increased by DEM supplementation in male, but not female, rats. The most striking finding of the study was that compared to males, females had extremely elevated kidney calcium concentrations, and that the elevation was exacerbated by arsenic deprivation. DEM supplementation also exacerbated the accumulation of calcium in the kidney of the female rats. The response of the rat to both DEM and arsenic was, for many variables, dependent on gender. This gender dependence may be explained by the differences in methionine metabolism between male and female rats. Thus, arsenic deprivation apparently can manifest itself differently depending on gender.

Analysis of Variance↗
PubMedDate not supplied

Mechanisms of arsenic-induced cell transformation.

Arsenic is a well-established carcinogen in humans, but there is little evidence for its carcinogenicity in animals and it is inactive as an initiator or tumor promoter in two-stage models of carcinogenicity in mice. Studies with cells in culture have provided some possible mechanisms by which arsenic and arsenical compounds may exert a carcinogenic activity. Sodium arsenite and sodium arsenate were observed to induce morphological transformation of Syrian hamster embryo cells in a dose-dependent manner. The trivalent sodium arsenite was greater than tenfold more potent than the pentavalent sodium arsenate. The compounds also exhibited toxicity; however, transformation was observed at nontoxic as well as toxic doses. At low doses, enhanced colony forming efficiency of the cells was observed. To understand the mechanism of arsenic-induced transformation, the genetic effects of the two arsenicals were examined over the same doses that induced transformation. No arsenic-induced gene mutations were detected at two genetic loci. However, cell transformation and cytogenetic effects, including endoreduplication, chromosome aberrations, and sister chromatid exchanges, were induced by the arsenicals with similar dose responses. These results support a possible role for chromosomal changes in arsenic-induced transformation. The two arsenic salts also induced another form of mutation-gene amplification. Both sodium arsenite and sodium arsenate induced a high frequency of methotrexate-resistant 3T6 cells, which were shown to have amplified copies of the dihydrofolate reductase gene.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2000

Arsenic metabolism in seaweed-eating sheep from Northern Scotland.

Cation exchange and anion exchange liquid chromatography were coupled to an ICP-MS and optimised for the separation of 13 different arsenic species in body fluids (arsenite, arsenate, dimethylarsinic acid (DMAA), monomethylarsonic acid (MMAA), trimethylarsine oxide (TMAO), tetramethylarsonium ion (TMA), arsenobetaine (AsB), arsenocholine (AsC), dimethylarsinoyl ethanol (DMAE) and four common dimethylarsinoylribosides (arsenosugars). The arsenic species were determined in seaweed extracts and in the urine and blood serum of seaweed-eating sheep from Northern Scotland. The sheep eat 2-4 kg of seaweed daily which is washed ashore on the most northern Island of Orkney. The urine, blood and wool of 20 North Ronaldsay sheep and kidney, liver and muscle from 11 sheep were sampled and analysed for their arsenic species. In addition five Dorset Finn sheep, which lived entirely on grass, were used as a control group. The sheep have a body burden of approximately 45-90 mg arsenic daily. Since the metabolism of arsenic species varies with the arsenite and arsenate being the most toxic, and organoarsenic compounds such as arsenobetaine the least toxic compounds, the determination of the arsenic species in the diet and their body fluids are important. The major arsenic species in their diet are arsenoribosides. The major metabolite excreted into urine and blood is DMAA (95 +/- 4.1%) with minor amounts of MMAA, riboside X, TMA and an unidentified species. The occurrence of MMAA is assumed to be a precursor of the exposure to inorganic arsenic, since demethylation of dimethylated or trimethylated organoarsenic compounds is not known (max. MMAA concentration 259 microg/L). The concentrations in the urine (3179 +/- 2667 microg/L) and blood (44 +/- 19 microg/kg) are at least two orders of magnitude higher than the level of arsenic in the urine of the control sheep or literature levels of blood for the unexposed sheep. The tissue samples (liver: 292 +/- 99 microg/kg, kidney: 565 +/- 193 microg/kg, muscle: 680 +/- 224 microg/kg) and wool samples (10470 +/- 5690 microg/kg) show elevated levels which are also 100 times higher than the levels for the unexposed sheep.

Animals↗
PubMed2003

Arsenic exposure in the wine growing industry in ten French departments.

OBJECTIVES: This study investigated exposure to arsenic, a carcinogenic fungicide used in wine growing. METHODS: The first phase compared urinary arsenic excretion of controls and workers exposed at the end of application. The second phase measured the increase in urinary arsenic excretion during the first day of use. RESULTS: A significant increase in urinary arsenic excretion was observed in arsenic applicators during the first phase. Urinary arsenic concentrations exceeded the American Conference of Governmental Industrial Hygienists (ACGIH) exposure index in one-third of the workers. The second phase showed a significant increase in urinary arsenic excretion by the first day of application. A closed tractor cabin provided a protective effect, but the efficacy of individual protection equipment was not demonstrated. CONCLUSION: This study showed the difficulties of achieving the effective protection of arsenic applicators and has led to the banning of the use of arsenic in French vineyards.

Adult↗
PubMed2006

Individual lifetime exposure to inorganic arsenic using a space-time information system.

OBJECTIVES: A space-time information system (STIS) based method is introduced for calculating individual-level estimates of inorganic arsenic exposure over the adult life-course. STIS enables visualization and analysis of space-time data, overcoming some of the constraints inherent to spatial-only Geographic Information System software. The power of this new methodology is demonstrated using data from southeastern Michigan where 8% of the population is exposed to arsenic >10 microg/l (the World Health Organization guideline) in home drinking water. METHODS: Participants (N=440) are members of a control group in a population-based bladder cancer case-control study in southeastern Michigan and were recruited by phone using random digit dialing. Water samples were collected and analyzed for arsenic at current residence and participants were required to answer questions concerning lifetime mobility history and dietary habits. Inorganic arsenic concentrations were estimated at past residences and workplaces, and in select foods. Fluid and food consumption data were integrated with mobility histories and arsenic concentrations to calculate continuous estimates of inorganic arsenic intake over the adult life-course. RESULTS: Estimates of continuous arsenic exposure are displayed, making use of both participant age and calendar year as measures of time. Results illustrate considerable temporal variability in individual-level exposure, with 26% of the participants experiencing a change in drinking water arsenic concentration of at least +/-10 microg/l over their adult lives. The average cumulative intake over the adult life-course ranges from 2.53 x 10(4)-1.30 x 10(5) microg, depending on the selected exposure metric. CONCLUSIONS: The STIS-based exposure assessment method allows for flexible inclusion of different parameters or alternative formulations of those parameters, thus enabling the calculation of different exposure metrics. This flexibility is particularly useful when additional exposure routes are considered, input datasets are updated, or when a scientific consensus does not exist regarding the proper formulation of the exposure metric. These results demonstrate the potential of STIS as a useful tool for calculating continuous estimates of adult lifetime exposure to arsenic or other environmental contaminants for application in exposure and risk assessment.

Adult↗
PubMed1991

Glutathione-dependent biliary excretion of arsenic.

This study aimed to clarify whether glutathione (GSH) plays a role in the hepatobiliary transport of arsenic. For this purpose, the biliary excretion of 74As was measured in urethane-anaesthetized rats for 2 hr after the administration of labelled sodium arsenite (50 mumol/kg, i.v.) or arsenate (150 mumol/kg, i.v.) and under the influence of sulfobromophthalein (BSP), indocyanine green (ICG) or diethyl maleate (DEM) which are known to diminish hepatobiliary transport of GSH. Although the biliary excretion of arsenic was different after arsenite and arsenate administration in terms of quantity (19% vs 6% of dose in 2 hr, respectively) and time course, arsenic excretion responded similarly to BSP (50 mumol/kg, i.v.), ICG (25 mumol/kg, i.v.) or DEM (4 mumol/kg, i.p.) irrespective of the injected arsenical. Initially the biliary excretion of arsenic in rats with either arsenite or arsenate was significantly reduced, but then moderately increased by BSP and, more lastingly, depressed by ICG, whereas it was virtually abolished by DEM. The responses of arsenic excretion to BSP, ICG and DEM were related, both proportionally and temporally, to the effects exerted by these agents on the hepatobiliary transport of GSH, as assessed by the biliary excretion of non-protein thiols. These findings indicate that the biliary excretion of arsenic after the administration of either arsenite or arsenate is dependent on the hepatobiliary transport of GSH. Transport of arsenic as a GSH complex may account for the GSH dependence of biliary arsenic excretion.

Animals↗
PubMed1983

Arsenic metabolites in urine and feces of hamsters pretreated with PCB.

High pressure liquid chromatography and graphite tube atomizing atomic absorption spectrometry were used to quantify monomethyl arsonic acid (MMA), dimethyl arsinic acid (DMA), and inorganic arsenic (IA: arsenite plus arsenate) in the urine and feces of male and female hamsters pretreated with a single ip injection of PCB (100 mg/kg) and 4 days later given a single po dose of arsenite (10 mg As/kg). Approximately 17 to 23% and 35 to 63% of the arsenic given was eliminated in the urine and feces, respectively, during the 5 days after the administration of arsenic. Both DMA and MMA were found in the urine but only MMA was detected in the feces, as methylated metabolite. Fecal excretion of arsenic was significantly larger in female than in males. PCB influenced the metabolism of arsenic by significantly increasing the proportion of DMA excreted into the urine of female hamsters during the 5 days after the arsenic administration, but did not alter the total amount of arsenic metabolites in any group of male or female hamsters. PCB did not affect the cumulative amounts of fecal arsenic in any group, although the excretion in the PCB-treated group of females reached the maximum level 1 day earlier than in the controls. These results suggest that the metabolism of arsenic may be regulated by certain sex-relating factors which are influenced by PCB.

Animals↗